ABSTRACT
The diversity of inputs that guide sexual fate during development is both intriguing and daunting. In the field of fish biology, the study of sex determination is of great importance. For example, in aquaculture, sexually dimorphic growth rates and overall size leads to one sex being more marketable than the other. Moreover, for breeding purposes it is important to maintain balanced sex ratios. Furthermore, sex determination is sensitive to environmental factors, such as temperature and contaminants, which can lead to skewed sex ratios, intersexes and sterility in wild or farmed fish. The gonad is typically the first organ to exhibit morphological signs of sexual dimorphism and therefore is likely to be the primary organ system whose fate is controlled by the sex determination cues in many fish species. Additionally, the sexual fate of the gonad has been shown to fully or partially control organismal sex differentiation. Thus, understanding the genetic regulation of gonadal sex differentiation is critical in studies of fish sex determination. This review summarizes recent knowledge of genes expressed during gonadal sex differentiation in gonochoristic teleost fish. Three species are discussed, which serve as excellent model systems for probing teleost sex differentiation: the Oreochromis niloticus, Oryzias latipes and Danio rerio. The similarities and differences between gonadal gene expression in these three species and in comparison to mammals suggest conserved roles during vertebrate gonadal sex differentiation. In the future, it will be essential to develop tools to assay the function of genes expressed during gonadal sex differentiation in fish.
Subject(s)
Cichlids/growth & development , Gonads/growth & development , Oryzias/growth & development , Sex Differentiation/genetics , Zebrafish/growth & development , Animals , Cichlids/genetics , Female , Gene Expression Regulation, Developmental , Male , Oryzias/genetics , Sex Ratio , Zebrafish/geneticsABSTRACT
Lateral organs produced by shoot apical and flower meristems exhibit a fundamental abaxial-adaxial asymmetry. We describe three members of the YABBY gene family, FILAMENTOUS FLOWER, YABBY2 and YABBY3, isolated on the basis of homology to CRABS CLAW. Each of these genes is expressed in a polar manner in all lateral organ primordia produced from the apical and flower meristems. The expression of these genes is precisely correlated with abaxial cell fate in mutants in which abaxial cell fates are found ectopically, reduced or eliminated. Ectopic expression of either FILAMENTOUS FLOWER or YABBY3 is sufficient to specify the development of ectopic abaxial tissues in lateral organs. Conversely, loss of polar expression of these two genes results in a loss of polar differentiation of tissues in lateral organs. Taken together, these observations indicate that members of this gene family are responsible for the specification of abaxial cell fate in lateral organs of Arabidopsis. Furthermore, ectopic expression studies suggest that ubiquitous abaxial cell fate and maintenance of a functional apical meristem are incompatible.
Subject(s)
Arabidopsis Proteins , Arabidopsis/genetics , Cell Differentiation/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Amino Acid Sequence , Base Sequence , Body Patterning , Cloning, Molecular , Cotyledon/genetics , Gene Expression Regulation, Plant , Meristem , Molecular Sequence Data , Multigene Family , Mutation , Plant Leaves/genetics , Plants, Genetically Modified/genetics , Transcription Factors/geneticsABSTRACT
The paper reviews the results obtained with velnacrine, a cholinesterase inhibitor and potential Alzheimer's disease agents, in early clinical studies in healthy volunteers and patients with probable Alzheimer's disease (AD). In healthy subjects, the compound was demonstrated to reverse cognitive impairment induced by scopolamine. Single doses of velnacrine improved performance of patients with AD in simple recognition tasks and enhanced regional cerebral blood flow in prefrontal-parietal areas. In a short crossover-study, velnacrine was demonstrated to be significantly (< 0.05) superior to placebo in the cognitive behaviour subscale of the ADAS, a word recognition task and, in trend, also on the Clinical Global Impression of Improvement.
Subject(s)
Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/pharmacology , Tacrine/analogs & derivatives , Alzheimer Disease/complications , Alzheimer Disease/metabolism , Cholinesterase Inhibitors/pharmacokinetics , Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/chemically induced , Cognition Disorders/prevention & control , Double-Blind Method , Female , Humans , Male , Placebos , Scopolamine , Tacrine/pharmacokinetics , Tacrine/pharmacology , Tacrine/therapeutic use , Tomography, Emission-Computed, Single-PhotonABSTRACT
Clinical studies of cognitive effects of ACTH fragments carried out so far with ACTH (1-10) and (4-9) (Org. 2766) brought about inconsistent and partly disappointing results. Efficacy could not be demonstrated in patients with Alzheimer's disease (AD). A possible reason for these results is the low metabolic stability and low lipophilicity of these compounds. HOE 427 has a considerably prolonged metabolic stability, has a high lipophilicity, and is much more potent than are existing compounds in pharmacologic models of memory and learning. It also was proven to have significant effects on ACh metabolism. Single dose studies in groups of mildly cognitively impaired elderly subjects and in patients with AD showed slight but significant effects on attention and mood. The effects were less consistent in patients than in healthy subjects.
