Goldfish reproduction is coordinated by pheromones that are released by ovulating females and detected by males. Two highly potent pheromones, a dihydroxyprogesterone and a prostaglandin, previously have been identified, and their effects on goldfish behavior have been studied in depth. We have cloned goldfish olfactory epithelium cDNAs belonging to two multigene G-protein coupled receptor families as a step toward elucidating the molecular basis of pheromone recognition. One gene family (GFA) consists of homologs of putative odorant receptors (Ϸ320 residues) found in the olfactory epithelium of other fish and mammals. The other family (GFB) consists of homologs of putative pheromone receptors found in the vomeronasal organ (VNO) of mammals and also in the nose of pufferfish. GFB receptors (Ϸ840 residues) are akin to the V2R family of VNO receptors, which possess a large extracellular N-terminal domain and are homologs of calcium-sensing and metabotropic glutamate receptors. In situ hybridization showed that the two families of goldfish receptors are differentially expressed in the olfactory epithelium. GFB mRNA is abundant in rather compact cells whose nuclei are near the apical surface. In contrast, GFA mRNA is found in elongated cells whose nuclei are positioned deeper in the epithelium. Our findings support the hypothesis that the separate olfactory organ and VNO of terrestrial vertebrates arose in evolution by the segregation of distinct classes of neurons that were differentially positioned in the olfactory epithelium of a precursor aquatic vertebrate.A vast number of odorants can be discriminated by the olfactory system of vertebrates (1-3). Electrophysiological studies have revealed that olfaction is mediated by the interplay of neural signals arising from many different kinds of sensory neurons (4). The cloning of three large multigene families of putative odorant and pheromone receptors has revolutionized the field (5-9). What is the mechanism of this remarkable combinatorial recognition process? Goldfish are an attractive model system for the study of this intriguing problem for several reasons. First, the reproductive behavior of goldfish is coordinated by several pheromones of known structure. Preovulatory females release 17␣,20␤-dihydroxy-4-pregnen-3-one and related hormones a day before ovulation (10-11). The detection of these steroids by the olfactory system of males leads to the production of sperm and seminal fluid. Shortly after ovulation, females release prostaglandin F 2␣ and derivatives, which immediately trigger courtship behavior by males (12). Second, these pheromones are effective at very low concentration. The threshold is in the picomolar to nanomolar range, compared with micromolar to millimolar for most olfactants. Third, olfaction in fish may be simpler than in mammals, given the 10-fold smaller size of their receptor repertoire (13).Aquatic vertebrates have a single kind of olfactory epithelium, whereas terrestrial vertebrates possess a vomeronasal organ (VNO) in addition...

In view of the incomplete understanding of the impact of mechanism of injury on TBI outcomes, as demonstrated in the current review, new research studies are required to improve evidence-based TBI guidelines tailored especially for penetrating injuries.

Radiosurgery is now the preferred treatment modality for many intracranial disease processes. Although almost 50 years have passed since it was introduced as a tool to treat neurological disease, investigations into its effects on normal tissues of the central nervous system are still ongoing. The need for these continuing studies must be underscored. A fundamental understanding of the brain parenchymal response to radiosurgery would permit development of strategies that would enhance and potentiate the radiosurgical treatment effects on diseased tissue while mitigating injury to normal structures. To date, most studies on the response of the central nervous system to radiosurgery have been performed on brain tissue in the absence of pathological lesions, such as benign tumors or metastases. Although instructive, these investigations fail to emulate the majority of clinical scenarios that involve radiosurgical treatment of specific lesions surrounded by normal brain parenchyma. This article is the first in a two-part series that addresses the brain parenchyma's response to radiosurgery. This first article analyzes the histological, radiographic, and molecular data gathered regarding the brain parenchymal response to radiosurgery and aims to suggest future studies that could enhance our understanding of the topic. The second article in the series begins by discussing strategies for radiosurgical therapeutic enhancement. It concludes by focusing on strategies for mitigation and repair of radiation-induced brain injury.