Effect of excess and deficiency of vitamin A on the utilization of FFA by liver and skeletal muscle.

Fatty acid metabolism in liver and skeletal muscle has been studied in rats treated with high doses of vitamin A and in those made vitamin A-deficient. Ingestion of 30,000 IU of vitamin A for two days resulted in increased incorporation of palmitate-1-14C into triglycerides but not into phospholipids. Accumulation of hepatic triglycerides was observed in vitamin A-fed rats. Deficiency of vitamin A did not cause any change in the triglyceride or phospholipid content of the liver. The rate of hepatic fatty acid oxidation and ketogenesis was markedly increased in vitamin A-fed rats. The experimental evidence indicated that vitamin A may have a stimulatory effect on these processes apart from that exerted by the high plasma FFA level in vitamin A-fed rats. Oxidation of palmitate-1-14C into C32 by skeletal muscle (latissimus dorsi) was also increased as a result of vitamin A administration. Vitamin A deficiency did not cause any change in fatty acid oxidation by liver and skeletal muscle. Hepatic palmitoyl-CoA synthetase activity was decreased in vitamin A-deficient rats. The results presented suggest that vitamin A may be required for the uptake and utilization of fatty acids by liver and akeletal muscle.     

Pore Dynamics and Conductance of RyR1 Transmembrane Domain

Ryanodine receptors (RyR) are calcium release channels, playing a major role in the regulation of muscular contraction. Mutations in skeletal muscle RyR (RyR1) are associated with congenital diseases such as malignant hyperthermia and central core disease (CCD). The absence of high-resolution structures of RyR1 has limited our understanding of channel function and disease mechanisms at the molecular level. Previously, we have reported a hypothetical structure of the RyR1 pore-forming region, obtained by homology modeling and supported by mutational scans, electrophysiological measurements, and cryo-electron microscopy. Here, we utilize the expanded model encompassing six transmembrane helices to calculate the RyR1 pore region conductance, to analyze its structural stability, and to hypothesize the mechanism of the Ile4897 CCD-associated mutation. The calculated conductance of the wild-type RyR1 suggests that the proposed pore structure can sustain ion currents measured in single-channel experiments. We observe a stable pore structure on timescales of 0.2 μs, with multiple cations occupying the selectivity filter and cytosolic vestibule, but not the inner chamber. We further suggest that stability of the selectivity filter critically depends on the interactions between the I4897 residue and several hydrophobic residues of the neighboring subunit. Loss of these interactions in the case of polar substitution I4897T results in destabilization of the selectivity filter, a possible cause of the CCD-specific reduced Ca²⁺ conductance.     

Comparative evaluation of various control schemes for fed-batch fermentation

The crucial problem associated with control of fed-batch fermentation process is its time-varying characteristics. A successful controller should be able to deal with this feature in addition to the inherent nonlinear characteristics of the process. In this work, various schemes for controlling the glucose feed rate of fed-batch baker's yeast fermentation were evaluated. The controllers evaluated are fixed-gain proportional-integral (PI), scheduled-gain PI, adaptive neural network and hybrid neural network PI. The difference between the specific carbon dioxide evolution rate and oxygen uptake rate (Q_c-Q_o) was used as the controller variable. The evaluation was carried out by observing the performance of the controllers in dealing with setpoint tracking and disturbance rejection. The results confirm the unsatisfactory performance of the conventional controller where significant oscillation and offsets exist. Among the controllers considered, the hybrid neural network PI controller shows good performance.     

Design of high-power,broadband 180° pulses and mixing sequences for fast MAS solid state chemical shift correlation NMR spectroscopy

An approach for the design of high-power, broadband 180° pulses and mixing sequences for generating dipolar and scalar coupling mediated ¹³C–¹³C chemical shift correlation spectra of isotopically labelled biological systems at fast magic-angle spinning frequencies without ¹H decoupling during mixing is presented. Considering RF field strengths in the range of 100–120 kHz, as typically available in MAS probes employed at high spinning speeds, and limited B ₁ field inhomogeneities, the Fourier coefficients defining the phase modulation profile of the RF pulses were optimised numerically to obtain broadband inversion and refocussing pulses and mixing sequences. Experimental measurements were carried out to assess the performance characteristics of the mixing sequences reported here.