Comparison of X-Ray Crystal Structure of the 30S Subunit-Antibiotic Complex with NMR Structure of Decoding Site Oligonucleotide-Paromomycin Complex

AbstractAminoglycoside antibiotics that bind to 16S ribosomal RNA in the aminoacyl-tRNA site (A site) cause misreading of the genetic code and inhibit translocation. Structures of an A site RNA oligonucleotide free in solution and bound to the aminoglycosides paromomycin or gentamicin C1a have been determined by NMR. Recently, the X-ray crystal structure of the entire 30S subunit has been determined, free and bound to paromomycin. Distinct differences were observed in the crystal structure, particularly at A1493. Here, the NMR structure of the oligonucleotide-paromomycin complex was determined with higher precision and is compared with the X-ray crystal structure of the 30S subunit complex. The comparison shows the validity of both structures in identifying critical interactions that affect ribosome function

Studies on Pre-slaughter Handling of Pigs and its Relationship to Meat Quality

End of Project ReportsTwo quality defects of pork which are affected by preslaughter handling are PSE (Pale Soft Exudative) and DFD (Dark Firm Dry) meat. The incidence of PSE pork is mainly a function of the breed of pig but short-term stressful handling before slaughter and feeding too close to slaughter are also involved. DFD meat is a result of prolonged stressful handling. PSE meat is pale and uneven in colour and exudes fluid making it unattractive in the retail display while dark meat appears stale and is prone to bacterial spoilage. After slaughter muscle metabolism continues and muscle glycogen is converted to lactic acid reducing meat pH. Prolonged stress results in glycogen depletion, pre-slaughter feeding results in elevated levels. Colour may be assessed subjectively by eye or objectively by a meter colour but pH of the meat is closely related to colour and measurement of pH at 45 minutes post-slaughter is frequently used to predict ultimate colour and pH. The objective of this study was to examine pre-slaughter handling practices and their relationship with meat quality (pH, colour). In the first trial, a survey of the amounts of stomach contents in pigs at slaughter in two factories found similar amounts to comparable surveys in France and the UK. It was concluded that most pigs had been fasted for an adequate time before delivery. The relationship between the amount of stomach contents and meat quality in this survey was poor. In the second trial, pigs from the Moorepark herd fed by either a computerised wet feeding system or an ad libitum dry feed system were slaughtered after overnight fasting or with feed available up to loading for transport to the factory, two to three hours before slaughter. There was no difference between feeding systems in meat colour or pH but fasted pigs, on both feeding systems, had darker meat and meat of a higher pH. In the third and fourth trials a survey of transport vehicles was carried out and meat quality of pigs delivered in modern and old-type vehicles was compared. Most trucks examined (78%) were four years old or more. Few had modern hydraulic lifting gear for the top decks. Space allowances during transportation were generally adequate but delays in unloading could, in warm weather, cause stress on pigs. There was little evidence for an effect of vehicle on meat quality parameters but day to day variation in carcass temperature and pH suggested a need for further research on factory influences on meat quality. Feeding of Magneium Aspartate to pigs for the last 5 days prior to slaughter has been shown, in Australia, to have a beneficial effect on meat colour and drip loss. In the final trial in this study Mg Asp had no effect on meat quality parameters.European Union Structural Funds (EAGGF

Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death.

Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer

The Effect of Short-Term Vitamin D Supplementation on Calcium Status in Vitamin D Insufficient Renal Transplant Recipients at Risk of Hypercalcaemia

Vitamin D insufficiency is highly prevalent amongst renal transplant recipients and in observational studies is associated with adverse outcomes. Hypercalcaemia, usually due to persistent hyperparathyroidism, also commonly occurs in this population and often coexists with vitamin D insufficiency. However, concern that vitamin D supplementation might exacerbate the pre-existing hypercalcaemia often leads clinicians to avoid vitamin D supplementation in such patients. This feasibility study aimed to quantify the effect on serum calcium of short-term low- dose cholecalciferol supplementation in a group of renal transplant recipients with a recent history of serum calcium levels >10 mg/dL

Diagnostic and prognostic significance of exercise-induced premature ventricular complexes in men and women: A four year follow-up

Two hundred eighty patients (197 men and 83 women) with normal rest electrocardiograms and no history of prior myocardial infarction were referred for evaluation of chest pain. It was found that exercise-induced premature ventricular complexes had a lower sensitivity, specificity, positive predictive value and negative predictive value in predicting significant coronary artery disease than exercise-induced ST segment depression greater than or equal to 1 mm. The incidence of exercise-induced premature ventricular complexes was not significantly different in patients with no significant coronary artery disease, single vessel disease or multivessel disease. The site of origin of exercise-induced premature ventricular complexes was not helpful in predicting the presence or severity of coronary artery disease. At a mean follow-up period of 47.1 months, exercise-induced premature ventricular complexes did not predict coronary events (cardiac death or nonfatal myocardial infarction) in men or women

Pre-pregnancy predictors of hypertension in pregnancy among Aboriginal and Torres Strait Islander women in north Queensland, Australia; a prospective cohort study

BACKGROUND Compared to other Australian women, Indigenous women are frequently at greater risk for hypertensive disorders of pregnancy. We examined pre-pregnancy factors that may predict hypertension in pregnancy in a cohort of Aboriginal and Torres Strait Islander women in north Queensland. METHODS Data on a cohort of 1009 Indigenous women of childbearing age (15–44 years) who participated in a 1998–2000 health screening program in north Queensland were combined with 1998–2008 Queensland hospitalisations data using probabilistic data linkage. Data on the women in the cohort who were hospitalised for birth (n = 220) were further combined with Queensland perinatal data which identified those diagnosed with hypertension in pregnancy. RESULTS Of 220 women who gave birth, 22 had hypertension in the pregnancy after their health check. The mean age of women with and without hypertension was similar (23.7 years and 23.9 years respectively) however Aboriginal women were more affected compared to Torres Strait Islanders. Pre-pregnancy adiposity and elevated blood pressure at the health screening program were predictors of a pregnancy affected by hypertension. After adjusting for age and ethnicity, each 1 cm increase in waist circumference showed a 4% increased risk for hypertension in pregnancy (PR 1.04; 95% CI; 1.02-1.06); each 1 point increase in BMI showed a 9% adjusted increase in risk (1.09; 1.04-1.14). For each 1 mmHg increase in baseline systolic blood pressure there was an age and ethnicity adjusted 6% increase in risk and each 1 mmHg increase in diastolic blood pressure showed a 7% increase in risk (1.06; 1.03-1.09 and 1.07; 1.03-1.11 respectively). Among those free of diabetes at baseline, the presence of the metabolic syndrome (International Diabetes Federation criteria) predicted over a three-fold increase in age-ethnicity-adjusted risk (3.5; 1.50-8.17). CONCLUSIONS Pre-pregnancy adiposity and features of the metabolic syndrome among these young Aboriginal and Torres Strait Islander women track strongly to increased risk of hypertension in pregnancy with associated risks to the health of babies.Sandra K Campbell, John Lynch, Adrian Esterman and Robyn McDermot

Electrophysiologic actions and antifibrillatory efficacy of subacute left stellectomy in a conscious, post-infarction canine model of ischemic ventricular fibrillation

The autonomic nervous system appears to modulate ventricular arrhythmias associated with acute myocardial ischemia. This study investigated the electrophysiologic effects and antifibrillatory actions of subacute left stellectomy in a conscious, post-infarction canine model of sudden cardiac death.Twenty-two dogs with a previous anterior wall myocardial infarction and inducible ventricular arrhythmias were randomized to undergo either left stellectomy (n = 12) or remain as sham-denervated controls (n = 10). Five to 7 days post left stellectomy, there were no significant changes in heart rate, electrocardiographic intervals or ventricular refractoriness compared to sham-denervated controls. Acute posterolateral ischemia was produced in left stellectomy and sham-denervated dogs by anodal current-induced thrombosis via a previously positioned electrode in the left circumflex coronary artery. Ventricular fibrillation developed within 1 hour of the onset of ischemia (early ventricular fibrillation) in 3/12 (25%) left stellectomy dogs versus 8/10 (80%) sham-denervated controls (P P = 0.072). Small differences in regional myocardial norepinephrine content, which is a marker for neuronal integrity, occurred in the mid-posterolateral and mid-anteroseptal regions of the left ventricle after left stellectomy. Overall norepinephrine concentration after left stellectomy was 409.70 +/- 9.90 ng/g vs 428.07 +/- 10.84 ng/g in sham controls (P = NS).In summary, subacute left stellectomy significantly reduces the incidence of ventricular fibrillation occurring within 1 hour of the onset of acute posterolateral ischemia at a distance to a previous myocardial infarction in conscious dogs, and tends to reduce the ischemic post-infarction mortality at 24 hours after the onset of ischemia. This protective effect of left stellectomy is not due to any alteration in cardiac electrophysiologic parameters measured prior to the development of acute posterolateral ischemia, nor is it related to regional denervation as determined by myocardial tissue concentration of residual norepinephrine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28039/1/0000478.pd

Anaesthesia of three young grey seals (Halichoerus grypus) for fracture repair

Three young grey seals (Halichoerus grypus) were presented separately for fracture repair to the veterinary teaching hospital of University College Dublin. The seals were premedicated with a combination of pethidine, midazolam and atropine; anaesthesia was induced with propofol via the front flipper vein and maintained with sevoflurane or isoflurane in oxygen. One of the seals did not breathe spontaneously after anaesthesia; a cardiac arrest, resulting in death, occurred after several hours of mechanical ventilation. Post-mortem examination revealed a severe lungworm infestation and parasitic pneumonia in this animal. The two other seals recovered uneventfully from anaesthesia