While several strategies can stimulate axonal regeneration within a site of spinal cord injury, the growth of axons is generally disorganized and random. Biocompatible scaffolds that guide and maintain the native organization of axons regenerating through an injury site could be of importance in enhancing recovery of the nervous system after injury. Here we report a novel fabrication process for templated agarose nerve guidance scaffolds composed of uniaxial channels of precise diameter and wall thickness extending through their full length. When tested in an in vivo model of spinal cord injury, scaffolds exhibit excellent integration with host tissue and support linear axonal growth through their channels. Further, when loaded with bone marrow stromal cells genetically engineered to secrete brain-derived neurotrophic factor (BDNF), the number of linear penetrating axons is significantly enhanced. The templating process can be useful in fabricating nerve guidance scaffolds for both central and peripheral nerve injuries, or any materials application requiring a precise array of linearly oriented channels.

Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL)

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Ras is a low-molecular-weight guanine nucleotide (GDP/GTP)-binding protein that transduces signals for growth and differentiation in eukaryotes. In mammals, the importance of Ras in regulating growth is underscored by the observation that activating mutations in ras genes are found in many animal tumors. Colletorichum trifolii is a filamentous fungal pathogen of alfalfa which causes anthracnose disease. To investigate signaling pathways that regulate growth and development in this fungus, a gene encoding a Ras homolog (CT-Ras) was cloned from C. trifolii. CT-Ras exhibited extensive amino acid similarity to Ras proteins from higher and lower eukaryotes. A single amino acid change resulting in mutationally activated CT-Ras induced cellular transformation of mouse (NIH 3T3) fibroblasts and tumor formation in nu/nu mice. In Colletotrichum, mutationally activated CT-Ras induced abnormal hyphal proliferation and defects in polarized growth, and significantly reduced differentiation in a nutrient-dependent manner. These results show that C. trifolii Ras is a functional growth regulator in both mammals and fungi, and demonstrate that proper regulation of Ras is required for normal fungal growth and development.