Minimal distance transformations between links and polymers: Principles and examples

The calculation of Euclidean distance between points is generalized to one-dimensional objects such as strings or polymers. Necessary and sufficient conditions for the minimal transformation between two polymer configurations are derived. Transformations consist of piecewise rotations and translations subject to Weierstrass-Erdmann corner conditions. Numerous examples are given for the special cases of one and two links. The transition to a large number of links is investigated, where the distance converges to the polymer length times the mean root square distance (MRSD) between polymer configurations, assuming curvature and non-crossing constraints can be neglected. Applications of this metric to protein folding are investigated. Potential applications are also discussed for structural alignment problems such as pharmacophore identification, and inverse kinematic problems in motor learning and control.Comment: Submitted to J. Phys.:Condens. Matte

Antifungal Activity of Selenium Nanoparticles Synthesized by Bacillus species Msh-1 Against Aspergillus fumigatus and Candida albicans

Background: Fungal infections affect various parts of the body and can be difcult to treat. Aspergillus infection causes a spectrum of diverse diseases particularly in lung according to host immunity. The two major entities are invasive pulmonary aspergillosis and chronic pulmonary aspergillosis. Candida infections can be superfcial or invasive. Superfcial infections often affect the skin or mucous membranes. However, invasive fungal infections are often life-threatening. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs. Objectives: In the present study, the antifungal activity of biogenic selenium nanoparticles (Se NPs) against Aspergillus fumigatus and Candida albicans was investigated. Materials and Methods: Se-reducing bacteria previously identifed as Bacillus sp. MSh-1 were used for the intracellular biosynthesis of elemental Se NPs. The shape, size, and purity of the extracted NPs were determined with various instrumental techniques. The nanoparticles antifungal characterization mainly derives from the following pathways: (i) to generate sustained flux of nano-ions from the compounds that deposited on special substrates or imbedded in colloidal or semisolid matrices. (ii) To transport active those ions to sensitive targets on plasma membrane of fungi. Results: The results of energy-dispersive X-ray demonstrated that the purifed NPs consisted of only Se. In addition, transmission electron micrographs showed that 120- to 140-nm spherical Se NPs were the most common. An antifungal assay was performed with a standard Clinical and Laboratory Standards Institute broth microdilution method. Minimum inhibitory concentration (MIC) measurements of the antifungal activity of the Se NPs against C. albicans (70 μg/mL) and A. fumigatus (100 μg/mL) showed that yeast cells were more sensitive than mold cells. Conclusions: The MICs against A. fumigatus (100 μg/mL) and C. albicans (70 μg/mL) showed that biogenic Se NPs are useful antifungal agents

The ITGB6 gene: its role in experimental and clinical biology.

Integrin αvβ6 is a membrane-spanning heterodimeric glycoprotein involved in wound healing and the pathogenesis of diseases including fibrosis and cancer. Therefore, it is of great clinical interest for us to understand the molecular mechanisms of its biology. As the limiting binding partner in the heterodimer, the β6 subunit controls αvβ6 expression and availability. Here we describe our understanding of the ITGB6 gene encoding the β6 subunit, including its structure, transcriptional and post-transcriptional regulation, the biological effects observed in ITGB6 deficient mice and clinical cases of ITGB6 mutations

Amelogenesis Imperfecta; Genes, Proteins And Pathways

Amelogenesis imperfecta (AI) is the name given to a heterogeneous group of conditions characterised by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discoloured, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light. Mutations in the gene AMELX, encoding an extracellular matrix protein secreted by ameloblasts during enamel formation, were first identified as a cause of AI in 1991. Since then, mutations in at least eighteen genes have been shown to cause AI presenting in isolation of other health problems, with many more implicated in syndromic AI. Some of the encoded proteins have well documented roles in amelogenesis, acting as enamel matrix proteins or the proteases that degrade them, cell adhesion molecules or regulators of calcium homeostasis. However, for others, function is less clear and further research is needed to understand the pathways and processes essential for the development of healthy enamel. Here, we review the genes and mutations underlying AI presenting in isolation of other health problems, the proteins they encode and knowledge of their roles in amelogenesis, combining evidence from human phenotypes, inheritance patterns, mouse models and in vitro studies. An LOVD resource (http://dna2.leeds.ac.uk/LOVD/) containing all published gene mutations for AI presenting in isolation of other health problems is described. We use this resource to identify trends in the genes and mutations reported to cause AI in the 270 families for which molecular diagnoses have been reported by 23rd May 2017. Finally we discuss the potential value of the translation of AI genetics to clinical care with improved patient pathways and speculate on the possibility of novel treatments and prevention strategies for AI

A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta

We identified a family in which pitted hypomineralized amelogenesis imperfecta (AI) with premature enamel failure segregated in an autosomal recessive fashion. Whole-exome sequencing revealed a missense mutation (c.586C>A, p.P196T) in the I-domain of integrin-beta6 (ITGB6), which is consistently predicted to be pathogenic by all available programmes and is the only variant that segregates with the disease phenotype. Furthermore, a recent study revealed that mice lacking a functional allele of Itgb6 display a hypomaturation AI phenotype. Phenotypic characterization of affected human teeth in this study showed areas of abnormal prismatic organization, areas of low mineral density and severe abnormal surface pitting in the tooth's coronal portion. We suggest that the pathogenesis of this form of AI may be due to ineffective ligand binding of ITGB6 resulting in either compromised cell-matrix interaction or compromised ITGB6 activation of transforming growth factor-beta (TGF-beta) impacting indirectly on ameloblast-ameloblast interactions and proteolytic processing of extracellular matrix proteins via MMP20. This study adds to the list of genes mutated in AI and further highlights the importance of cell-matrix interactions during enamel formation

The role of alpha v beta 6 integrin in enamel biomineralization

Tooth enamel has the highest degree of biomineralization of all vertebrate hard tissues. During the secretory stage of enamel formation, ameloblasts deposit an extracellular matrix that is in direct contact with ameloblast plasma membrane. Although it is known that integrins mediate cell-matrix adhesion and regulate cell signaling in most cell types, the receptors that regulate ameloblast adhesion and matrix production are not well characterized. Thus, we hypothesized that αvβ6 integrin is expressed in ameloblasts where it regulates biomineralization of enamel. Human and mouse ameloblasts were found to express both β6 integrin mRNA and protein. The maxillary incisors of Itgb6-/- mice lacked yellow pigment and their mandibular incisors appeared chalky and rounded. Molars of Itgb6-/- mice showed signs of reduced mineralization and severe attrition. The mineral-to-protein ratio in the incisors was significantly reduced in Itgb6-/- enamel, mimicking hypomineralized amelogenesis imperfecta. Interestingly, amelogenin-rich extracellular matrix abnormally accumulated between the ameloblast layer of Itgb6-/- mouse incisors and the forming enamel surface, and also between ameloblasts. This accumulation was related to increased synthesis of amelogenin, rather than to reduced removal of the matrix proteins. This was confirmed in cultured ameloblast-like cells, which did not use αvβ6 integrin as an endocytosis receptor for amelogenins, although it participated in cell adhesion on this matrix indirectly via endogenously produced matrix proteins. In summary, integrin αvβ6 is expressed by ameloblasts and it plays a crucial role in regulating amelogenin deposition/turnover and subsequent enamel biomineralization.Dentistry, Faculty ofGraduat