Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity

The regulated delivery of AMPA-type glutamate receptors (AMPARs) to synapses is an important mechanism underlying synaptic plasticity. Here, we ask whether the synaptic scaffolding protein PSD-95 (postsynaptic density 95) participates in AMPAR incorporation during two forms of synaptic plasticity. In hippocampal slice cultures, the expression of PSD-95-green fluorescent protein (PSD-95-GFP) increases AMPAR currents by selectively delivering glutamate receptor 1 (GluR1)-containing receptors to synapses, thus mimicking long-term potentiation (LTP). Mutational analysis shows that the N terminal of PSD-95 including the first two PDZ [PSD-95/Discs large (Dlg)/zona occludens-1 (ZO-1)] domains is necessary and sufficient to mediate this effect. Further supporting a role in synaptic plasticity, wild-type PSD-95 occludes LTP and dominant negative forms block LTP. Moreover, we demonstrate that PSD-95 also participates in AMPAR delivery during experience-driven plasticity in vivo. In the barrel cortex from experience-deprived animals, the expression of PSD-95-GFP selectively increases AMPAR currents, mimicking experience-driven plasticity. In nondeprived animals, PSD-95-GFP produces no additional potentiation, indicating common mechanisms between PSD-95-mediated potentiation and experience-driven synaptic strengthening. A dominant negative form of PSD-95 blocks experience-driven potentiation of synapses. Pharmacological analysis in slice cultures reveals that PSD-95 acts downstream of other signaling pathways involved in LTP. We conclude that PSD-95 controls activity-dependent AMPAR incorporation at synapses via PDZ interactions not only during LTP in vitro but also during experience-driven synaptic strengthening by natural stimuli in vivo

Increase in hospital admissions for acute childhood asthma in Cape Town, 1978 - 1990

To determine whether hospital admissions for acute childhood asthma were rising in Cape Town in line with the experience of other countries, Red Cross War Memorial Children's Hospital's records for the period 1978 - 1990 were analysed. These were compared with total admissions for non-surgical causes and lower respiratory tract illness as well as those for bronchiolitis and pneumonia. Asthma admissions showed a sharp upward trend from 1978 to 1984, a slower rise through 1987 and a levelling off since. The profile of hospital admissions for respiratory illness was also analysed. Black children were under-represented among asthma admissions compared with those for pneumonia. Asthma admissions occurred throughout the year but showed seasonal peaks in May and November. Reasons for these trends and patterns are discussed, as well as hypotheses for further research into the epidemiology of asthma in South Africa

Notification of pesticide poisoning in the western Cape, 1987 - 1991

There is a paucity of data on pesticide-related morbidity and mortality in South Africa. A review of notifications to the western Cape office of the Department of National Health and Population Development from 1987 to 1991 was undertaken to describe the epidemiological profile of pesticide poisoning in the region. Two hundred and twenty five cases of pesticide poisoning were identified, of which the majority were from rural areas. Farmers, farm workers and their families were most frequently involved in poisoning events, which included accidents arising outside of workplace production (44%), self-inflicted injury (35%) and direct occupational contamination (11%). Farm pesticide stores were the most frequent source of pesticide and a seasonal variation in the trend of poisoning events could be discerned; this corresponded to agricultural spraying practices in the region. The mortality rate was significantly higher among those with self-inflicted injury, particularly farm workers. A concurrent review of hospital admissions for 1991 found that 78% of cases had not been notified. In view of the key role of surveillance in reducing pesticide-related morbidity and mortality, a call is made to improve notification of pesticide poisoning so as to facilitate control of an important potential public health problem

Lattice Effects in Crystal Evaporation

We study the dynamics of a stepped crystal surface during evaporation, using the classical model of Burton, Cabrera and Frank, in which the dynamics of the surface is represented as a motion of parallel, monoatomic steps. The validity of the continuum approximation treated by Frank is checked against numerical calculations and simple, qualitative arguments. The continuum approximation is found to suffer from limitations related, in particular, to the existence of angular points. These limitations are often related to an adatom detachment rate of adatoms which is higher on the lower side of each step than on the upper side ("Schwoebel effect").Comment: DRFMC/SPSMS/MDN, Centre d'Etudes Nucleaires de Grenoble, 25 pages, LaTex, revtex style. 8 Figures, available upon request, report# UBFF30119

Underrecognition and undertreatment of asthma in Cape Town primary school children

Background. In view of the high local prevalence of asthma, the extent of recognition and appropriate managementof childhood asthma was studied in a large suburban area of Cape Town.Design. Cross-sectional study based on random community sample of schools.Method. 1955 parents of sub B pupils from 16 schools completed a questionnaire, followed by: (f) an interview of parents of 348 symptomatic children; and (if) bronchial responsiveness testing on 254 children. the final case group consisted of 242 children with reported asthma or multiple asthma symptoms on both questionnaires. Children in whom asthma was acknowledged were compared with those in whom it was not.Results. Overall, any past or current ('ever') asthma was acknowledged by respondents in only 53% of the children, and current asthma in only 37.1%. While most children had received treatment in the previous 12 months, 66.1% of therecognised group were on current treatment (23.2% on daily treatment), compared with 37% of the unrecognised group (3% daily). Salbutamol and theophylline syrups were the most common types of medication, while inhalers and antiinflammatory medications were underused. Only a minority of parents reported the child ever having used a peak flow meter, or volunteered knowledge of preventive measures. Current treatment, and to a lesser degree recognition of asthma by parents, were more common among children on medical aid and of higher socio-eonomic status.Conclusions. These findings suggest that ways need to be found: (i) to increase the use of current asthma treatment guidelines by practitioners; (ii) to provide access to comprehensive care by children not on medical aid; and (iii) to improve education of parents in home management measures such as severity assessment and avoidance of smoking, allergen and dietary triggers

Spiral surface growth without desorption

Spiral surface growth is well understood in the limit where the step motion is controlled by the local supersaturation of adatoms near the spiral ridge. In epitaxial thin-film growth, however, spirals can form in a step-flow regime where desorption of adatoms is negligible and the ridge dynamics is governed by the non-local diffusion field of adatoms on the whole surface. We investigate this limit numerically using a phase-field formulation of the Burton-Cabrera-Frank model, as well as analytically. Quantitative predictions, which differ strikingly from those of the local limit, are made for the selected step spacing as a function of the deposition flux, as well as for the dependence of the relaxation time to steady-state growth on the screw dislocation density.Comment: 9 pages, 3 figures, RevTe

Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression

In the tumour microenvironment, cancer cells directly interact with both the immune system and the stroma. It is firmly established that the immune system, historically believed to be a major part of the body's defence against tumour progression, can be reprogrammed by tumour cells to be ineffective, inactivated, or even acquire tumour promoting phenotypes. Likewise, stromal cells and extracellular matrix can also have pro-and anti-tumour properties. However, there is strong evidence that the stroma and immune system also directly interact, therefore creating a tripartite interaction that exists between cancer cells, immune cells and tumour stroma. This interaction contributes to the maintenance of a chronically inflamed tumour microenvironment with pro-tumorigenic immune phenotypes and facilitated metastatic dissemination. A comprehensive understanding of cancer in the context of dynamical interactions of the immune system and the tumour stroma is therefore required to truly understand the progression toward and past malignancy.Comment: 36 pages, 4 figures, 1 tabl