For example, more than 35 susceptibility loci have been identifie

For example, more than 35 susceptibility loci have been identified for type 2 diabetes and 32 for

obesity thus far. However, the causal gene and variant at a specific linkage disequilibrium block is often unclear. Using a combination of different mouse alleles, we can greatly facilitate the understanding of which candidate gene at a particular disease locus is associated with the disease in humans, and also provide functional analysis of variants through an allelic series, including analysis of hypomorph and hypermorph point mutations, and knockout and overexpression alleles. The phenotyping of these alleles for specific traits of interest, in combination with the functional analysis of the genetic variants, may reveal the molecular and cellular mechanism of action of these disease variants, and ultimately lead to the identification of novel therapeutic strategies for common human diseases. In this Commentary, BAY 73-4506 ic50 we

discuss the progress of GWAS in identifying common disease loci for metabolic disease, and the use of the mouse as a model to confirm candidate genes and provide mechanistic insights.”
“Tissue transplantation is a well-established tool for the treatment of degenerative and malignant disorders, yet its use in clinical practice is hampered by the need for human-leukocyte-antigen-compatible donors and a shortage of suitable graft tissue. The discovery

of human embryonic stem cells a decade ago raised hopes that a universal resource learn more for the cell-based treatment of various conditions would soon become available. embryonic Rapamycin clinical trial stem cells derived by somatic-cell nuclear transfer or parthenogenesis can provide human-leukocyte-antigen-matched cells, which may be transplanted without the need for immunosuppressive treatment. However, technical hurdles and ethical concerns about use of oocytes and involvement of embryos have limited the clinical use of these cells. An alternative approach involves adult somatic cells being reprogrammed to enter a pluripotent state. such manipulation of these readily available cells has enabled derivation of patient-specific, pluripotent stem-cell lines, without progression through the blastocyst stage. This review critically analyzes the currently available methods for the generation of pluripotent stem cells, and discusses prospects for their clinical use.”
“We present a systematic computational analysis of the complex, electromechanically driven surface dynamics of voids in thin films of face-centered cubic metals for < 100 >-oriented film planes characterized by four-fold symmetry of surface diffusional anisotropy. The voids are located at an edge of the metallic thin film, and the film is subjected simultaneously to an external electric field and an anisotropic biaxial tensile stress.

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