Wnt signaling represents a highly versatile signaling system, which plays diverse and critical roles in various aspects of neural development. Sensory neurons of the dorsal root ganglia require Wnt signaling for initial cell-fate determination as well as patterning and synapse formation. Here we report that Wnt signaling pathways persist in adult sensory neurons and play a functional role in their sensitization in a pathophysiological context. We observed that Wnt3a recruits the Wnt-calcium signaling pathway and the Wnt planar cell polarity pathway in peripheral nerves to alter pain sensitivity in a modality-specific manner and we elucidated underlying mechanisms. In contrast, biochemical, pharmacological, and genetic studies revealed lack of functional relevance for the classical canonical β-catenin pathway in peripheral sensory neurons in acute modulation of nociception. Finally, this study provides proof-of-concept for a translational potential for Wnt3a-Frizzled3 signaling in alleviating disease-related pain hypersensitivity in cancer-associated pain in vivo.
Twins were diagnosed by ultrasound in a 29-year-old woman. The cesarean delivery revealed at first a mature girl with a large benign sacrococcygeal teratoma and then a healthy boy. X-ray and CT examinations of the teratoma showed pelvic and lower limb bones. A mature teratoma-tridermoma (weight 475 g) containing the underdeveloped lower half of a human body was confirmed during surgery and verified morphologically. The fraternal twins, i.e., the girl operated upon and her brother, have been followed for 5 years and are without any complaints. They have normal neurological function.
HMDS treatment and subsequent air drying provides good quality scanning electron micrographs that reveal both endothelial patterns and the layered architecture of stented vessels. The disadvantage of HMDS drying may be a shrinkage and distortion similar to other drying agents. Ease of handling, low cost, and a high rate of success are advantages that favor HMDS desiccation over other drying methods.
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