'Sheltered disruption' of Neurospora crassa MOM22, an essential component of the mitochondrial protein import complex

MOM22 is a component of the protein import complex of the mitochondrial outer membrane of Neurospora crassa. Using the newly developed procedure of 'sheltered disruption', we created a heterokaryotic strain harboring two nuclei, one with a null allele of the mom-22 gene and the other with a wild-type allele. Homokaryons bearing the mom-22 disruption could not be isolated, suggesting that mom-22 is an essential gene. The mutant nucleus can be forced to predominate in the heterokaryon through the use of specific nutritional and inhibitor resistance markers. Cultivation of the heterokaryon under conditions favoring the mutant nucleus resulted in selective depletion of MOM22. MOM22-depleted cells did not grow and contained mitochondria with an altered morphology and protein composition. Protein import into isolated, MOM22-depleted mitochondria was abolished for most precursor proteins destined for all subcompartments. In contrast, precursors of MOM19, MOM22 and MOM72 became inserted normally into the outer membrane, defining a novel MOM22-independent import pathway which remained intact in mutant mitochondria. Furthermore, the specific binding of the ADP/ATP carrier to the outer membrane was unaffected, but subsequent transport across the outer membrane did not occur. Our data show that MOM22 is an essential component of Neurospora cells specifically required for the biogenesis of mitochondria.     

Cognitive shifting as a predictor of progress in social understanding in high-functioning adolescents with autism: a prospective study

The pyrolytic behavior of inulin, a (2-->1)-linked fructofuranan, is described. Parallel investigations of the pyrolysis of glucose and of fructose were conducted to supplement the inulin results and to aid comparison with previous results from glucans. Effects of neutral and basic additives are emphasized. As with glucans, the addition of such additives (especially basic) increases the yields of the one-, two-, and three-carbon products (as well as of hexosaccharinolactones), while generally decreasing the yields of anhydro sugar and furan derivatives. The former products include glycolaldehyde, acetol, dihydroxy-acetone, acetic acid, formic acid, and lactic acid. Mechanistic speculations are made regarding the origins of these compounds, as well as of furan derivatives and saccharinic acid lactones. Parallels with alkaline degradation are considered.     

On solving constrained optimization problems with neural networks:a penalty method approach

Deals with the use of neural networks to solve linear and nonlinear programming problems. The dynamics of these networks are analyzed. In particular, the dynamics of the canonical nonlinear programming circuit are analyzed. The circuit is shown to be a gradient system that seeks to minimize an unconstrained energy function that can be viewed as a penalty method approximation of the original problem. Next, the implementations that correspond to the dynamical canonical nonlinear programming circuit are examined. It is shown that the energy function that the system seeks to minimize is different than that of the canonical circuit, due to the saturation limits of op-amps in the circuit. It is also noted that this difference can cause the circuit to converge to a different state than the dynamical canonical circuit. To remedy this problem, a new circuit implementation is proposed.     

Lung function measurement in general practice: a comparison of the Escort spirometer with the Micromed turbine spirometer and the mini-Wright peak flow meter

It is important that new types of spirometer for widespread clinical use are pragmatically evaluated in primary care. This study compared measurements taken by a new portable Fleisch pneumotachograph spirometer (known as the Escort) with those of the commonly used mini-Wright peak flow meter and the Micromed Pocket turbine spirometer. A pragmatic study was conducted in two phases during routine surgeries at Aldermoor Health Centre, Southampton. Phase I compared the new spirometer with the mini-Wright peak flow meter and Phase 2 compared the new spirometer and the turbine spirometer. One hundred patients aged 5-88 years (56 patients with a history of chronic respiratory complaints and 44 patients without) entered Phase 1, and 100 patients aged 6-82 years (62 patients with a history of chronic respiratory complaints and 38 patients without) entered Phase 2. Each patient contributed only once to each phase, but some entered both phases on separate occasions. Ninety-five percent limits of agreement (mean +/- SD) were wide for all comparisons. Graphical plots revealed trends towards higher Escort values as mean values rose compared with both mini-Wright and turbine readings for peak expiratory flow rate and forced expiratory volume in one second. Possible over-reading of peak expiratory flow rate with the mini-Wright meter at low mean values was also seen. Readings taken with these different types of meter cannot be interchanged with confidence in clinical practice. The clinical significance of the theoretically more accurate measures of lung function produced with the new meter, and indeed of spirometry itself, needs further investigation.     

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminal renal failure were treated with low doses (average 0.36 micrograms/day) of calcitriol up to the time of renal transplantation, which was performed before dialysis had been initiated. A transiliac bone biopsy was obtained both at the start and at the end of the treatment period, the latter coinciding with renal transplantation. All patients who started calcitriol treatment at a creatinine clearance (Ccr) above 30 ml/min had normal bone histology at the time of transplantation, but this was not observed when calcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bone level is obtained only if prophylactic administration is started early in the course of renal failure.     

Minimal invasive therapy of aneurysms of the superficial femoral artery and the popliteal artery

Percutaneous stent placement has been described for treatment of aneurysms as an alternative to surgical therapy. Literature reports of percutaneous minimal invasive therapy of peripheral aneurysms shall be reviewed and compared with our own results. Six male patients (51-69 years) with femoropopliteal occlusions related to aneurysms were treated percutaneously. In two cases Wallstents and in four cases polyester-covered nitinol stents were applicated. A clinical investigation including doppler-ultrasound was performed 24 hrs, 1, 3, 6, 12 and 24 months after the intervention. Stent placement succeeded in all cases. No adjunctive surgical treatment was necessary. Ankle-brachial-index (ABI) improved from 0.22 +/- 0.2 before to 0.74 +/- 0.2 24 hours after the intervention. One patient was lost for follow-up (Wallstent). A decrease of ABI and additional intraarterial angiography revealed stent-graft occlusion within one month (n = 2) and within three months (n = 1). One of these cases was successfully recanalized with local fibrinolysis therapy. In three patients patency of the stent persisted for 24 (+/- 2) months follow-up with three-vessel-supply of the calf. These results warrant further investigations for this minimal invasive method of percutaneous stent deployment as an alternative to surgical bypass treatment of femoropopliteal aneurysms. Time of hospitalization was reduced. At this time, surgical treatment of peripheral vascular aneurysms is gold standard.     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact (n = 9) and SAD (n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 +/- 1.4 (SE) mmHg during the prepace state to 23.2 +/- 2.9 mmHg in the heart failure state in intact dogs (P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 +/- 2.2 mmHg from a control level of 4.2 +/- 1.9 mmHg i SAD dogs (P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 +/- 8.9 beats/min in intact dogs and 136.1 +/- 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 +/- 21.6 vs. 320.6 +/- 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 +/- 44.2 pg/ml) and SAD (644.0 +/- 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these date that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.