Serotonin: A transmitter candidate in the vertebrate retina

It has been established by a combination of high performance liquid chromatographic and immunohistochemical methods that serotonin occurs in amacrine cell bodies and terminals situated in the inner plexiform layer of the frog retina, where enzymes for the synthesis of the same amine are also present. Potassium stimulation causes a release of previously accumulated radioactive serotonin by the retina. These findings support the opinion that serotonin is a retinal transmitter.     

RCAS-RNAi: A loss-of-function method for the developing chick retina

Background  

The embryonic chick provides an excellent model system for studies of development. However, it has lacked an efficient loss-of-function method for studies of gene function.     

Influenza in animals: its possible public health significance

There often appears to be an epidemiologic association between human and animal influenza outbreaks. Serologic studies have demonstrated that the influenza viruses of avian, swine, and equine species may be closely related to the influenza viruses of man. Isolation of viruses common to man and animals have been claimed. It appears certain that human and animal influenza viruses do sometimes share common antigens. The exact relationship between human and animal influenza is not yet understood and will require additional study.     

Serotonin synthesis and its light-dark variation in the rat retina

Retinal circadian rhythms are driven by an intrinsic oscillator, using chemical signals such as melatonin, secreted by photoreceptor cells. The purpose of the present work was to identify the origin of serotonin, the precursor of melatonin, in the retina of adult rat, where no immunoreactivity for serotonin or tryptophan hydroxylase had ever been detected. To demonstrate local synthesis of serotonin in the rat retina, substrates of tryptophan hydroxylase, the first limiting enzyme in the serotonin pathway, have been used. Tryptophan, in the presence of an inhibitor of aromatic amino acid decarboxylase, enhanced 5-hydroxytryptophan levels, whereas alpha-methyltryptophan, a competitive substrate inhibitor, was hydroxylated into alpha-methyl-5-hydroxytryptophan. Tryptophan hydroxylase substrate concentration was higher in the dark period than in the light period, and formation of hydroxylated compounds was increased. The presence of tryptophan hydroxylase mRNA in the rat retina was confirmed by RT-PCR. Taken together, the results support the local synthesis of serotonin by tryptophan hydroxylation, this metabolic pathway being required more critically when 5-HT is used for melatonin synthesis.     

A dynamic model of the vertebrate retina

In this paper a mathematical model of the retina was proposed to clarify the spatio-temporal information processing mechanism in the retina of vertebrates. In order to explain spatio-temporal characteristics of an on-center receptive field of a ganglion cell, excitatory and inhibitory cell layers were introduced of which time lags increased with the lateral distance from a point of stimulation. The characteristics of this model were found to agree well with the physiological data: e.g., this model shows on-response to the input stimulus given on the center, off-response to the input on the surround, and on-off response to the input on the border between on- and off-response regions of the on-center field.     

‘Signs of the times’: confession and the semiotic production of inner truth

How is it that confession – a highly ritualized, dialogically structured speech act – appears to transparently reflect and reveal the inner states of confessants? This article explores this question by closely engaging select post‐Vatican II defences of the Sacrament of Penance, which lay out the requirements of ‘modern’ confession in striking detail. A close reading of these theological texts demonstrates that felicitous confession is the product of three correlated (meta‐)semiotic processes: (1) the figuration of the pentinent memory as a storehouse for sin; (2) the management of ritual time into discrete stages of ‘private’ meaning‐making and ‘public’ pronouncement; and (3) the erasure of the social scenery of the confessional utterance. In concert, these processes render indexical signs as iconic ones and, in so doing, naturalize confession as the cathartic revelation of inner truths, already constituted as such.     

GOPET: A tool for automated predictions of Gene Ontology terms

Background  

Vast progress in sequencing projects has called for annotation on a large scale. A Number of methods have been developed to address this challenging task. These methods, however, either apply to specific subsets, or their predictions are not formalised, or they do not provide precise confidence values for their predictions.     

Development of the crayfish retina: A light and electron microscopic study

The development of the crayfish retina was examined in embryos and first, second and third instars with both and light and electron microscope. Light microscopic observations indicate that differentiation begins at the posterior portion of the optic disc and progresses in an anterior direction. Development of screening pigment, dioptric elements, and rhabdoms all parallel this posterior to anterior gradient in the retina. Tracer studies in early embryos reveal that the retina is separated from the proximal neuropil regions by a distinct vascular space. This observation suggests that the source of new cells for the retina may not be the more proximal cell proliferation zone as previously indicated. It is proposed that mitotic activity within the retina and/or differentiation of cells from the anterior surface layer of the eye may be sources for addition of new cells to the retina. Proto-ommatidial clusters of seven retinula cells occur very early at the posterior region of the embryonic retina. Initially the receptor cells extend throughout the entire thickness of the retina, but later they withdraw from beneath the cornea to occupy only the proximal portion of the retina. Microvilli of the rhabdom arise from the centrally opposed membranes of the retinula cells in each cell cluster. Each new microvillus contains a core of fine filaments which extend out into the cytoplasm at its base. As development of the microvilli continues, the core filaments appear to be lost or altered, but the cytoplasmic bundles at the base of the microvilli persist.     

Gene therapy: progress and predictions

The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines.     

A molecular phenotype atlas of the zebrafish retina

The rasborine cyprinid Danio rerio (the zebrafish) has become a popular model of retinal function and development. Its value depends, in part, on validation of homologies with retinal cell populations of cyprinine cyprinids. This atlas provides raw and interpreted molecular phenotype data derived from computationally classified sets of small molecule signals from different cell types in the zebrafish retina: L-alanine, L-aspartate, L-glutamine, L-glutamate, glutathione, glycine, taurine and γ-aminobutyrate. This basis set yields an 8-dimensional signature for every retinal cell and formally establishes molecular signature homologies with retinal neurons, glia, epithelia and endothelia of other cyprinids. Zebrafish photoreceptor classes have been characterized previously: we now show their metabolic profiles to be identical to those of the corresponding photoreceptors in goldfish. The inner nuclear layer is partitioned into precise horizontal, bipolar and amacrine cell layers. The horizontal cell layer contains at least three and perhaps all four known classes of cyprinine horizontal cells. Homologues of cyprinid glutamatergic ON-center and OFF-center mixed rod-cone bipolar cells are present and it appears likely that all five classes are present in zebrafish. The cone bipolar cells defy simple analysis but comprise the largest fraction of bipolar cells, as in all cyprinids. Signature analysis reveals six molecular phenotypes in the bipolar cell cohort: most are superclasses. The amacrine cell layer is composed of ≈64% GABA+ and 35% glycine+ amacrine cells, with the remainder being sparse dopaminergic interplexiform cells and other rare unidentified neurons. These different amacrine cell types are completely distinct in the dark adapted retina, but light adapted retinas display weak leakage of GABA signals into many glycinergic amacrine cells, suggesting widespread heterocellular coupling. The composition of the zebrafish ganglion cell layer is metabolically indistinguishable from that in other cyprinids, and the signatures of glial and non-neuronal cells display strong homologies with those in mammals. As in most vertebrates, zebrafish Müller cells possess a high glutamine, low glutamate signature and contain the dominant pool of glutathione in the neural retina. The retinal pigmented epithelium shows a general mammalian signature but also has exceptional glutathione content (5–10 mM), perhaps required by the unusually high oxygen tensions of teleost retinas. The optic nerve and the marginal zone of the retina reveal characteristic metabolic specializations. The marginal zone is strongly laminated and its nascent neurons display their characteristic signatures before taking their place in the retina proper.     

The immunocompetence handicap hypothesis: testing the genetic predictions

The immunocompetence handicap hypothesis suggests that the immune system competes for resources with sexually selected ornaments; variation in ornaments might reflect genetic variation for immunocompetence. We tested this genetic prediction by mating scorpionfly females to males differing in the expression of a condition-dependent ornament trait, saliva secretion, and then comparing offspring immunocompetence. We found several indications of an immunocompetence handicap in our study: females had superior immunocompetence compared with males, the different immune traits were positively correlated, and there were indications of genetic variation in immune traits. However, we found no significant difference in the immunocompetence of offspring derived from males differing in ornament expression, only a tendency for sons of ornamented males to possess slightly better immunocompetence. The estimated effect of fathers on offspring immunocompetence was rather small, but it might be a sufficient benefit of female choice, provided that the costs of choice are small. We conclude that the genetic benefit of female choice is small concerning offspring immunocompetence, but the immunocompetence handicap principle might nevertheless work in scorpionflies.     

Modeling the adaptive immune system: predictions and simulations

MOTIVATION: Immunological bioinformatics methods are applicable to a broad range of scientific areas. The specifics of how and where they might be implemented have recently been reviewed in the literature. However, the background and concerns for selecting between the different available methods have so far not been adequately covered. SUMMARY: Before using predictions systems, it is necessary to not only understand how the methods are constructed but also their strength and limitations. The prediction systems in humoral epitope discovery are still in their infancy, but have reached a reasonable level of predictive strength. In cellular immunology, MHC class I binding predictions are now very strong and cover most of the known HLA specificities. These systems work well for epitope discovery, and predictions of the MHC class I pathway have been further improved by integration with state-of-the-art prediction tools for proteasomal cleavage and TAP binding. By comparison, class II MHC binding predictions have not developed to a comparable accuracy level, but new tools have emerged that deliver significantly improved predictions not only in terms of accuracy, but also in MHC specificity coverage. Simulation systems and mathematical modeling are also now beginning to reach a level where these methods will be able to answer more complex immunological questions.     

Retinoic acid in the formation of the dorsoventral retina and its central projections

Dynamic expression patterns of four retinoid-metabolizing enzymes create rapidly changing retinoic acid (RA) patterns in the emerging eye anlage of the mouse. First, a RA-rich ventral zone is set up, then a RA-poor dorsal zone, and finally a tripartite organization consisting of dorsal and ventral RA-rich zones separated by a horizontal RA-poor stripe. This subdivision of the retina into three RA concentration zones is directly visible as beta-galactosidase labeling patterns in retinas of RA-reporter mice. Because the axons of retinal ganglion cells transport the reporter product anterogradely, the central projections from dorsal and ventral retina can be visualized as two heavily labeled axon bundles. Comparisons of the axonal labeling with physiologic recordings of visual topography in the adult mouse show that the labeled axons represent the upper and the lower visual fields. The RA-poor stripe develops into a broad horizontal zone of higher visual acuity. Comparisons of the retina labeling with eye-muscle insertions show that the axis of the RA pattern lines up with the dorsoventral axis of the oculomotor system. These observations indicate that the dorsoventral axis of the embryonic eye anlage determines the functional coordinates of both vision and eye movements in the adult.