Implications of fragile X expression in normal males for the nature of the mutation

The fragile site at Xq27, associated with a common form of X-linked mental retardation (XLMR), is expressed in a variable proportion of the peripheral lymphocytes of affected males when the cells are cultured under thymidylate stress (Td stress) produced by folate or thymidylate deprivation. Some clinically normal males--transmitting males--are known to carry and transmit the fragile X mutation and yet show no cytogenetic expression in lymphocytes. Normal males with no family history of X-linked mental retardation express the site only rarely. When the fragile X chromosome from affected males is isolated in a rodent genetic background by somatic cell hybridization, the level of expression is similar to that seen in lymphocytes under Td stress. Here we show that X chromosomes from two transmitting males and two normal control males, all of which were fragile X negative in lymphocytes or lymphoblasts, could be made to express the fragile site in hybrids, although at levels that were below those seen in hybrids from affected males. Furthermore, transmitting males could be differentiated from normal males by their significantly higher expression rates when hybrids were exposed to caffeine before cytogenetic harvest. One male chimpanzee also showed low level expression in hybrid cells. These data suggest that the hybrid system lowers the threshold for fragile X expression, a fragile site at Xq27 may be present on all human and chimpanzee X chromosomes and constitutes a previously unrecognized common fragile site and the hybrid system with caffeine post-treatment can distinguish between the common Xq27 fragile site of control males, the occult mutant fragile site of a transmitting male, and the fully expressed fragile site of an affected male with XLMR. Thus the mutation producing XLMR may represent a multi-step alteration of a naturally occurring DNA sequence producing a continuum of cytogenetic expression and a threshold for clinical manifestation.     

Genetic dissection of monoamine neurotransmitter synthesis in Drosophila

The biogenic monoamine neurotransmitters octopamine, dopamine and serotonin have been detected in nervous tissue from many insects. We report here that intact Drosophila melanogaster brains, when incubated with the radioactive amino acids tyrosine and tryptophan, synthesized and accumulated labelled monoamines. In two mutant strains monoamine synthesis was abnormal. The per o mutation abolishes the normal circadian rhythm. Brains from per o flies, when incubated in tritiated tyrosine, accumulated one-third as much labelled octopamine as did brains from wild-type flies, but had normal dopamine and serotonin synthesis. In contrast, dopa decarboxylase (Ddc) mutations decreased dopamine and serotonin synthesis but did not affect octopamine synthesis. These results suggest that there are two different aromatic amino acid decarboxylases in Drosophila brains, one that decarboxylates L-dopa and 5-hydroxytryptophan and another that decarboxylates tyrosine. Direct measurement of L-dopa, 5-hydroxytryptophan and tyrosine decarboxylase activities in the different strains confirmed this suggestion.     

Motility and mechanosensitivity of macrocilia in the ctenophore Bero?

Mechanical activation of the microtubule sliding mechanism in cilia and flagella by local passive bending has been postulated to be essential for the initiation and propagation of bending waves along the axoneme. In addition, responsiveness of cilia to hydrodynamic forces imposed externally by their neighbours is thought to be responsible for metachronal coordination of ciliary activity, as well as for synchronal beating of component cilia within compound ciliary organelles. Direct tests of the mechanosensitivity of motile cilia are limited, but generally support these views. It remains problematical, however, whether mechanical interaction between cilia operates continuously during both the effective and recovery phases of the asymmetrical beat cycle. Moreover, the directional sensitivity and temporal responsiveness of motile cilia to mechanical stimuli have been explored in only a few cases. Finally, the continuous nature of the ciliary beat cycle has hindered investigation of the 'switch point hypothesis' in which doublet sliding is assumed to be activated sequentially on the two halves of the axoneme to produce bends in opposite directions. Here we report that macrocilia on the ctenophore Bero? beat discontinuously with separate effective and recovery strokes, resulting in 'split-cycle' waves of metachronal coordination. This new pattern of ciliary beating is used to investigate the motile responses of cilia to controlled mechanical stimuli during each phase of the beat cycle.     

SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones

The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.     

轮腿结合步态稳定裕度的研究

研究一种轮腿结合式步行机的步态特性和静态稳定裕度与步态参数间的关系，并对这类步态进行了计算机仿真。     

Evolution and ecological correlates of uniparental reproduction in freshwater snails

We review the spatial and temporal correlates of uniparental reproduction in freshwater snails as they pertain to the ecological hypotheses for the maintenance of biparental sex. The biogeographic evidence from two species (Potamopyrgus antipodarum andBulinus truncatus) presently supports the Red Queen hypothesis that biparental reproduction is selected as a way to reduce the risk to progeny of parasite attack. Uniparental reproduction in these species is associated with low levels of infection by parasites (castrating digenetic trematodes), suggesting that parthenogenesis or self-fertilization can replace cross-fertilization when the risk of infection is low. In addition, inB. truncatus, the opportunity for cross-fertilization coincides with the season in which parasite attack is highest. In a third species (Campeloma decisum), parthenogenetic reproduction is correlated with latitude and the presence of a non-castrating trematode that may prevent cross-fertilization; these patterns suggest that parthenogenesis has been selected as a mechanism to assure reproduction. Finally, we discuss the spotty taxonomic distribution of parthenogenetic species.     

On the pathway of the rectosphincteric reflex

In several rat models, including those with circular and semicircular rectal aganglionosis, the rectosphincteric reflex was examined. The reflex was confirmed to be essentially an intramural one and its route is considered to run mainly in the longitudinal and partly in the oblique directions.     

(3H) spiroperidol binding decreases in brains of rats infected with Venezuelan equine encephalomyelitis virus1

Summary After i.p. inoculation with the Guajira strain of Venezuelan equine encephalomyelitis virus a significant decrease in the density of (³H) spiroperidol binding sites in the striatum, midbrain and frontal cortex was observed. No changes in the affinity of the receptors could be demonstrated. This finding is compatible with neuronal degeneration caused by the viral infection.Acknowledgments. This work was partially supported by Condes-Luz and Fundacite-Zulia. Butaclamol isomers were a gift of Ayerst Laboratories, Montreal, Canada.     

Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat

In the feline gastrointestinal tract, the neuropeptides, substance P, VIP and PHI were investigated by specific radioimmunoassays and immunocytochemistry. The concentrations of all 3 peptides and the level of peptidergic innervation were significantly less in the anal sphincter than elsewhere, whereas no significant differences were seen between other sphincter and non-sphincter regions.