Phosphoinositide regulation of neuroexocytosis: adding to the complexity

Exocytosis of neurotransmitter containing vesicles supports neuronal communication. The importance of molecular interactions involving specific lipids has become progressively more evident and the lipid composition of both the synaptic vesicle and the pre-synaptic plasma membrane at the active zone has significant functional consequences for neurotransmitter release. Several classes of lipids have been implicated in exocytosis including polyunsaturated fatty acids and phosphoinositides. This minireview will focus on recent developments regarding the role of phosphoinositides in neurosecretion.

Relationship of body condition score and blood urea and ammonia to pregnancy in Italian Mediterranean buffaloes

The relationship of body condition score ( BCS) and blood urea and ammonia to pregnancy outcome was examined in Italian Mediterranean Buffalo cows mated by AI. The study was conducted on 150 buffaloes at 145 +/- 83 days in milk that were fed a diet comprising 14.8% crude protein, 0.9 milk forage units . kg(-1) dry matter and a non- structural carbohydrate/ crude protein ratio of 2.14. The stage of the oestrous cycle was synchronised by the Ovsynch- TAI programme and blood urea and ammonia levels were assessed on the day of AI. Energy corrected milk ( ECM) production and BCS were recorded bi- weekly. The pregnancy risk was 46.7% and was slightly lower in buffaloes with BCS < 6.0 and BCS > 7.5. There were no significant differences in ECM, urea and ammonia between pregnant and non- pregnant buffaloes. However, pregnancy outcome was higher ( P = 0.02) in buffaloes with blood urea < 6.83 mmol . L-1. The likelihood of pregnancy for buffaloes with low urea blood level was 2.6 greater than for high urea level and exposure to a high urea level lowered the probability of pregnancy by about 0.25. The findings indicate that buffaloes are similar to cattle and increased blood levels of urea are associated with reduced fertility when animals are mated by AI.

The complexity of p53 stabilization and activation

A number of proteins are activated by stress stimuli but none so spectacularly or with the degree of complexity as the tumour suppressor p53 (human p53 gene or protein). Once stabilized, p53 is responsible for the transcriptional activation of a series of proteins involved in cell cycle control, apoptosis and senescence. This protein is present at low levels in resting cells but after exposure to DNA-damaging agents and other stress stimuli it is stabilized and activated by a series of post-translational modifications that free it from MDM2 (mouse double minute 2 but used interchangeably to denote human also), a ubiquination ligase that ubiquitinates it prior to proteasome degradation. The stability of p53 is also influenced by a series of other interacting proteins. In this review, we discuss the post-translational modifications to p53 in response to different stresses and the consequences of these changes.

Development of a clinical and echocardiographic score for assigning risk of major events after exercise and dobutamine echocardiograms

The prognostic value of exercise (EXE) and dobutamine echocardiograms (DbE) has been well defined in large studies. However, while risk is determined by both clinical and echo features, no simple means of combining these data has been defined. We sought to combine these data into risk scores. Methods. At 3 expert centers, 7650 pts underwent standard EXE (n=5211) and DbE (w2439) for evaluation of known or suspected CAD and were followed for up to 10 years (mean 5-2) for major events (death or myocardial infarction). A subgroup of 2953 EXE and 1025 DbE pts was randomly selected to develop separate multivariate models for prediction of events. After simplication of each model for clinical use, models were validated in the remaining EXE and DbE pts. ResuI1s. The total number of events was 200 in the EXE and 225 in the DbE pts, of which 58 and 99 events occurred in the respective testing groups. The following regression equations gave equivalent results I” the testing and validation groups for both EXE and DbE; DbE = (Age’O.02) + (DM’l .O) + (Low RPP’0.6) + ([CHF+lschemia+Scar]‘O.7) EXE = ([DM+CHF]‘O.S) + O.S(lschemla #) + l.B(Scar#) - (METS0.19) (where each categorical variable scored 1 when present and 0 when absent, Ischemia# = 1 for l-2 VD. 6 for 3 VD; Scar# = 1 for 1-2 VD, 1.7 for 3 VD). The table summarizes the scores and equivalent outcomes for EXE and DbE. Conclusions. Risk scores based on clinical and EXE or DbE results may be used to quantify the risk of events during follow-up.