Changes in murine anorectum signaling across the life course

Background: Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.Methods: The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age‐related changes in nitric oxide and acetylcholine release.Key Results: Nitrergic relaxation increased between 3 and 6 months, peaked at 12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age‐related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age‐related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.Conclusions and Inferences: The decrease in nitrergic signaling with increasing age may contribute to the age‐related fecal impaction and constipation previously described in this model by partially obstructing defecation

Strategies for coping with the costs of inpatient care: a mixed methods study of urban and rural poor in Vadodara District, Gujarat, India

Background In India, coping mechanisms for inpatient care costs have been explored in rural areas, but seldom among urbanites. This study aims to explore and compare mechanisms employed by the urban and rural poor for coping with inpatient expenditures, in order to help identify formal mechanisms and policies to provide improved social protection for health care

Speckle techniques for determining stresses in moving objects

Laser speckle interferometry is a relatively new experimental technique which shows promise of alleviating many difficult problems in experimental mechanics. The method utilizes simple high-resolution photographs of the surface which is illuminated by coherent light. The result is a real-time or permanently stored whole-field record of interference fringes which yields a map of displacements in the object. In this thesis, the time-average theory using the Fourier transform is developed to present the application of this technique to measurement of in-plane displacement induced by the vibration of an object

Interstitial cell network volume is reduced in the terminal bowel of ageing mice

Ageing is associated with impaired neuromuscular function of the terminal gastrointestinal (GI) tract, which can result in chronic constipation, faecal impaction and incontinence. Interstitial cells of cajal (ICC) play an important role in regulation of intestinal smooth muscle contraction. However, changes in ICC volume with age in the terminal GI tract (the anal canal including the anal sphincter region and rectum)have not been studied. Here, the distribution, morphology and network volume of ICC in the terminal GI tract of 3‐to 4‐month‐old and 26‐to 28‐month‐old C57BL/6mice were investigated. ICC were identified by immunofluorescence labelling of wholemount preparations with an antibody against c‐Kit. ICC network volume was measured by software‐based 3D volume rendering of confocal Z stacks. A significant reduction in ICC network volume per unit volume of muscle was measured in aged animals. No age‐associated change in ICC morphology was detected. The thickness of the circular muscle layer of the anal sphincter region and rectum increased with age, while that in the distal colon decreased. These results suggest that ageing is associated with a reduction in the network volume of ICC in the terminal GI tract, which may influence the normal function of these regions

Development of basic theories and techniques for determining stresses in rotating turbine or compressor blades

A method for measuring in-plane displacement of a rotating structure by using two laser speckle photographs is described. From the displacement measurements one can calculate strains and stresses due to a centrifugal load. This technique involves making separate speckle photographs of a test model. One photograph is made with the model loaded (model is rotating); the second photograph is made with no load on the model (model is stationary). A sandwich is constructed from the two speckle photographs and data are recovered in a manner similar to that used with conventional speckle photography. The basic theory, experimental procedures of this method, and data analysis of a simple rotating specimen are described. In addition the measurement of in-plane surface displacement components of a deformed solid, and the application of the coupled laser speckle interferometry and boundary-integral solution technique to two dimensional elasticity problems are addressed

Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA–coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology