A constitutive model for cytoskeletal contractility of smooth muscle cells

The constitutive model presented in this article aims to describe the main bio-chemo-mechanical features involved in the contractile response of smooth muscle cells, in which the biochemical response is modelled by extending the four-state Hai–Murphy model to isotonic contraction of the cells and the mechanical response is mainly modelled based on the phosphorylation-dependent hyperbolic relation between isotonic shortening strain rate and tension. The one-dimensional version of the model is used to simulate shortening-induced deactivation with good agreement with selected experimental measurements. The results suggest that the Hai–Murphy biochemical model neglects the strain rate effect on the kinetics of cross-bridge interactions with actin filaments in the isotonic contractions. The two-dimensional version and three-dimensional versions of the model are developed using the homogenization method under finite strain continuum mechanics framework. The two-dimensional constitutive model is used to simulate swine carotid media strips under electrical field stimulation, experimentally investigated by Singer and Murphy, and contraction of a hollow airway and a hollow arteriole buried in a soft matrix subjected to multiple calcium ion stimulations. It is found that the transverse deformation may have significant influence on the response of the swine carotid medium. In both cases, the orientation of the maximal value of attached myosin is aligned with the orientation of maximum principal stress

Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

BACKGROUND: Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. METHODS: The present association study tested whether length variations in the second (more 3') polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO). In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. RESULTS: Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090). Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05). The prevalence of the long CAG repeat (>19 repeats) did not reach statistical significance in migraineurs (P = 0.15), nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively), or between MA vs MO (P = 0.40). CONCLUSION: This association study provides no evidence that length variations of the second polyglutamine array in the N-terminus of the KCNN3 channel exert an effect in the pathogenesis of migraine

Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

Fabricación de materiales compuestos con microestructuras complejas y propiedades mejoradas a partir de suspensiones

11 páginas, 12 figuras.-- Trabajo presentado al XII Congreso Nacional de Propiedades Mecánicas de Sólidos celebrado en Aránzazu-Guipúzcoa (España) en Septiembre de 2010.[EN]: Colloidal processing has demonstrated its suitability for manufacturing ceramics with a great variety of shapes, sizes and complex microstructures. Colloidal methods require the preparation of stable, homogeneous suspensions of the material to be shaped, so that the control of stability is fundamental. cerámicos con una gran variedad de formas y Similarly, metal powders and ceramic-metal mixtures can be succesfully processed by colloidal routes if sedimentation, on one hand, and dissolution and oxidation, on the other hand, are avoided or controlled. In this work some examples of the manufacture of ceramics and composites through a colloidal approach are shown, and the advantages of some simple, economic and reliable shaping techniques are discussed. It is demonstrated that denser and more homogeneous materials with finer and more uniform microstructures and hence, with cerámicos y compuestos mediante una better behavioural properties, can be obtained.[ES]: El procesamiento coloidal ha demostrado su eficacia en la fabricación de materiales cerámicos con una gran variedad de formas y tamaños y microestructuras complejas. Los métodos coloidales suponen la preparación de suspensiones estables y homogéneas del material a conformar, por lo que el control de la estabilidad es fundamental. De forma análoga, los polvos metálicos y las mezclas cerámica- metal se pueden procesar por vía coloidal si se asegura la estabilidad y se evitan o controlan la sedimentación, por una parte, y la disolución y oxidación, por otra. En este trabajo se muestran algunos ejemplos de fabricación de materiales cerámicos y compuestos mediante una aproximación coloidal y se discuten las ventajas de algunas técnicas de conformado sencillas, económicas y reproducibles. Todo ello contribuye a la obtención de materiales más densos y homogéneos, con microestructuras más finas y uniformes, y por tanto, con mejores propiedades de comportamiento.Este trabajo ha sido financiado por los Proyectos MAT2009-14369-C02-01 y PID600200-2009-5.Peer reviewe