Modified Cav1.4 Expression in the Cacna1fnob2 Mouse Due to Alternative Splicing of an ETn Inserted in Exon 2

The Cacna1fnob2 mouse is reported to be a naturally occurring null mutation for the Cav1.4 calcium channel gene and the phenotype of this mouse is not identical to that of the targeted gene knockout model. We found two mRNA species in the Cacna1fnob2 mouse: approximately 90% of the mRNA represents a transcript with an in-frame stop codon within exon 2 of CACNA1F, while approximately 10% of the mRNA represents a transcript in which alternative splicing within the ETn element has removed the stop codon. This latter mRNA codes for full length Cav1.4 protein, detectable by Western blot analysis that is predicted to differ from wild type Cav1.4 protein in a region of approximately 22 amino acids in the N-terminal portion of the protein. Electrophysiological analysis with either mouse Cav1.4wt or Cav1.4nob2 cDNA revealed that the alternatively spliced protein does not differ from wild type with respect to activation and inactivation characteristics; however, while the wild type N-terminus interacted with filamin proteins in a biochemical pull-down experiment, the alternatively spliced N-terminus did not. The Cacna1fnob2 mouse electroretinogram displayed reduced b-wave and oscillatory potential amplitudes, and the retina was morphologically disorganized, with substantial reduction in thickness of the outer plexiform layer and sprouting of bipolar cell dendrites ectopically into the outer nuclear layer. Nevertheless, the spatial contrast sensitivity (optokinetic response) of Cacna1fnob2 mice was generally similar to that of wild type mice. These results suggest the Cacna1fnob2 mouse is not a CACNA1F knockout model. Rather, alternative splicing within the ETn element can lead to full-length Cav1.4 protein, albeit at reduced levels, and the functional Cav1.4 mutant may be incapable of interacting with cytoskeletal filamin proteins. These changes, do not alter the ability of the Cacna1fnob2 mouse to detect and follow moving sine-wave gratings compared to their wild type counterparts

Effect of lift force and hydrodynamic torque on fluidisation of non-spherical particles

The aim of many industrial processes is to manipulate solid particle aggregates within gas suspensions. Prime examples of such processes include fluidised bed reactors, cyclone separators, and dust collectors. In recent years, fluidised bed reactors have been used in the gasification of biomass particles. When fluidised, these particles are subject to various hydrodynamic forces such as drag, lift and torque due to interactions with the fluid. Computational approaches, which can be used to replicate laboratory and industrial scale processes, offer a crucial method for the study of reactor design and for the formulation of optimal operating procedures. Until now, many computer models have assumed particles to be spherical whereas, in reality, biomass feedstocks typically consist of non-spherical particles. While lift and torque are of minimal importance for spherical particles, non-spherical particles experience varying lift force and torque conditions, depending on particle orientation relative to the direction of the fluid velocity. In this study, we present a numerical investigation on the effect of different lift force and torque correlations on fluidised spherocylindrical particles. We find that lift force has a significant influence on particle velocities parallel to the direction of gravity. On the other hand, particle orientation is dependent on hydrodynamic torque. Results from this numerical study provide new insight with regards to the dynamics of non-spherical particles that can be of paramount importance for industrial processes involving non-spherical particles.Complex Fluid ProcessingIntensified Reaction and Separation System

PREFACE AND ACKNOWLEDGEMENTS

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