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The Hedgehog (Hh) pathway regulates the growth of a subset of adult gliomas and better definition of Hh-responsive subtypes could enhance the clinical utility of monitoring and targeting this pathway in patients. Somatic mutations of the isocitrate dehydrogenase (IDH) genes occur frequently in WHO grades II and III gliomas and WHO grade IV secondary glioblastomas. Hh pathway activation in WHO grades II and III gliomas suggests that it might also be operational in glioblastomas that developed from lower grade lesions. To evaluate this possibility and to better define the molecular and histopathological glioma subtypes that are Hh-responsive, IDH genes were sequenced in adult glioma specimens assayed for an operant Hh pathway. The proportions of grades II–IV specimens with IDH mutations correlated with the proportions that expressed elevated levels of the Hh gene target PTCH1. Indices of an operational Hh pathway were measured in all primary cultures and xenografts derived from IDH-mutant glioma specimens, including IDH-mutant glioblastomas. In contrast, the Hh pathway was not operational in glioblastomas that lacked IDH mutation or history of antecedent lower-grade disease. IDH mutation is not required for an operant pathway however, as significant Hh pathway modulation was also measured in grade III gliomas with wild-type IDH sequences. These results indicate that the Hh pathway is operational in grades II and III gliomas and glioblastomas with molecular or histopathological evidence for evolvement from lower-grade gliomas. Lastly, these findings suggest that gliomas sharing this molecularly defined route of progression arise in Hh-responsive cell types.

Lundberg, C.J.; Lane, R.R., and Day, J.W., Jr., 2014. Spatial and temporal variations in nutrients and water-quality parameters in the Mississippi River-influenced Breton Sound estuary. Journal of Coastal Research, 30(2), 328-336. Coconut Creek (Florida), ISSN 0749-0208.The purpose of this study is to investigate the long-term temporal and spatial nutrient patterns in the Breton Sound estuary, an estuarine wetland complex in coastal Louisiana that is highly influenced by the Caernarvon river diversion. A water-quality data set spanning 8 years of monthly sampling was analyzed. Analysis of salinity mixing diagrams indicates the estuary to be a source of ammonium and chlorophyll a, and a sink for nitrate, total nitrogen, and total suspended sediments. The estuary served as either a source or sink for phosphate, total phosphorus, and silicate depending on season. The NO x loading rate ranged from 1.1 g N m À2 y À1 during fall to 4.9 g N m À2 y À1 during spring, with an overall mean of 3.5 g N m À2 y À1 . Nitrate removal efficiency varied seasonally, with highest efficiency during the fall (98%), summer (92%), and spring (87%) and lowest during the winter (74%). There was an inverse relationship between nutrient removal efficiency and nutrient loading rate. The results of this study indicate that the estuary is effective in water-quality amelioration through nitrate removal.ADDITIONAL INDEX WORDS: River diversion, removal efficiency, nitrate loading, water quality amelioration.

Malignant gliomas constitute a heterogeneous group of highly infiltrative glial neoplasms with distinct clinical and molecular features. Primary orthotopic xenografts recapitulate the histopathological and molecular features of malignant glioma subtypes in preclinical animal models. To model WHO grades III and IV malignant gliomas in transplantation assays, human tumor cells are xenografted into an orthotopic site, the brain, of immunocompromised mice. In contrast to secondary xenografts that utilize cultured tumor cells, human glioma cells are dissociated from resected specimens and transplanted without prior passage in tissue culture to generate primary xenografts. The procedure in this report details tumor sample preparation, intracranial transplantation into immunocompromised mice, monitoring for tumor engraftment and tumor harvesting for subsequent passage into recipient animals or analysis. Tumor cell preparation requires 2 hr and surgical procedure requires 20 min/animal. Video LinkThe video component of this article can be found at

Hedgehog signaling regulates the growth of malignant gliomas by a ligand dependent mechanism. The cellular source of Hedgehog ligand and mode of signaling have not been clearly defined due to the lack of methods to definitively identify neoplastic cells in glioma specimens. Using an antibody specific for mutant isocitrate dehydrogenase protein expression to identify glioma cells, we demonstrate that Sonic hedgehog ligand and the pathway components Patched1 and GLI1 are expressed in neoplastic cells. Further, Sonic hedgehog ligand production and GLI1 transcription factor expression occur in mutually distinct populations of neoplastic cells. These findings support a role for paracrine Hedgehog signaling in malignant gliomas.