Cellular basis for the response to second-order motion cues in Y retinal ganglion cells.

We perceive motion when presented with spatiotemporal changes in contrast (second-order cue). This requires linear signals to be rectified and then summed in temporal order to compute direction. Although both operations have been attributed to cortex, rectification might occur in retina, prior to the ganglion cell. Here we show that the Y ganglion cell does indeed respond to spatiotemporal contrast modulations of a second-order motion stimulus. Responses in an OFF ganglion cell are caused by an EPSP/IPSP sequence evoked from within the dendritic field; in ON cells inhibition is indirect. Inhibitory effects, which are blocked by tetrodotoxin, clamp the response near resting potential thus preventing saturation. Apparently the computation for second-order motion can be initiated by Y cells and completed by cortical cells that sum outputs of multiple Y cells in a directionally selective manner.     

Cellular basis for the differential response of mouse kallikrein genes to hormonal induction.

The expression of many mouse kallikrein genes in the salivary gland is sexually dimorphic and inducible in females by administration of testosterone or thyroxine. Induction is slow (3-7 days) and is accompanied by the non-uniform differentiation of the cell type expressing these genes from striated duct (SD) cells (female) to granular convoluted tubule (GCT) cells (male). One kallikrein gene, mGK-6, is expressed at an apparently constant total level in male and female and is not induced by either hormone. In situ hybridization histochemistry shows that all kallikrein genes analyzed exhibit uniform cellular distribution of expression in the SD cells of the female. The hormonally mediated differentiation of some, but not all, of these cells has different effects on kallikrein gene expression--mGK-6 is repressed while other kallikreins are induced--leading to non-uniform distribution of expression.     

Cellular basis of the role of diesel exhaust particles in inducing Th2-dominant response

There is growing evidence that diesel exhaust particles (DEP) can induce allergic diseases with increased IgE production and preferential activation of Th2 cells. To clarify the cellular basis of the role of DEP in the induction of Th2-dominant responses, we examined the effects of DEP on the cytokine production by T cells stimulated with anti-CD3/CD28 Ab and on that by monocyte-derived dendritic cells (MoDCs) stimulated with CD40L and/or IFN-gamma. We examined IFN-gamma, IL-4, IL-5, IL-8, and IL-10 produced by T cells and TNF-alpha, IL-1beta, IL-10, and IL-12 produced by MoDCs using real-time PCR analysis or by ELISA. To highlight the effects of DEP, we compared the effects of DEP with those of dexamethasone (DEX) and cyclosporin A (CyA). DEP significantly suppressed IFN-gamma mRNA expression and protein production, while it did not affect IL-4 or IL-5 mRNA expression or protein production. The suppressive effect on IFN-gamma mRNA expression was more potent than that of DEX and comparable at 30 mug/ml with 10(-7) M CyA. The suppressive effect on IFN-gamma production was also more potent than that of either DEX or CyA. DEP suppressed IL-12p40 and IL-12p35 mRNA expression and IL-12p40 and IL-12p70 production by MoDCs, while it augmented IL-1beta mRNA expression. Finally, by using a thiol antioxidant, N-acetyl cysteine, we found that the suppression of IFN-gamma production by DEP-treated T cells was mediated by oxidative stress. These data revealed a unique characteristic of DEP, namely that they induce a Th2 cytokine milieu in both T cells and dendritic cells.     

Cellular and molecular basis for endometriosis-associated infertility

Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%?C15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman??s reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis.     

Genetic basis of olfactory communication in primates

The genes involved in olfactory communication in mammals via the vomeronasal system are summarized, and studies investigating these genes in primates are reviewed. Only five potentially functional vomeronasal receptor genes (V1RL s) have been found in humans, and only one of these (V1RL1) has been studied in other primates. V1RL1 has become a pseudogene repeatedly during primate evolution, but patterns of natural selection on primate V1RL genes demonstrate that this gene family diverged under natural selection throughout at least part of primate evolution. Evolution of the TRP2 gene, which encodes for an ion channel that is important in vomeronasal organ (VNO) signalling, strongly suggests that this signalling function was lost in ancestral Catarrhines. Overall, much work remains to be done to elucidate the repertoire of genes that are involved in pheromonal communication, particularly in Strepsirhines. Such studies promise unique insights into the evolution of this modality.     

Mechanisms underlying olfactory neuronal connectivity in Drosophila-the atonal lineage organizes the periphery while sensory neurons and glia pattern the olfactory lobe

Patterning of the antennal lobe of adult Drosophila occurs through a complex interaction between sensory neurons, glia, and central neurons of larval and adult origin. Neurons from the olfactory sense organs are organized into distinct fascicles lined by glial cells. The glia originate from one of the three types of sensory lineages-specified by the proneural gene atonal. Gain-of-function as well as loss-of-function analysis validates a role for cells of the Atonal lineage in the ordered fasciculation of sensory neurons. Upon entry of the antennal nerve to central regions, sensory neurons at first remain closely associated with central glia which lie around the periphery of the lobe anlage. Coincident with the arrival of sensory neurons into the brain, glial precursors undergo mitosis and neural precursors expressing Dachshund appear around the lobe. Sensory neurons and glial cells project into the lobe at around the same time and are likely to coordinate the correct localization of different glomeruli. The influence of sensory neurons on the development of the olfactory lobe could serve to match and lock peripheral and central properties important for the generation of olfactory behavior.     

Cellular basis of neurogenesis in the brain of crayfish,Procambarus clarkii: Neurogenic complex in the olfactory midbrain from hatchlings to adults

Neurogenesis in the central olfactory pathway of decapod crustaceans persists throughout life. Here we describe the structural basis of neurogenesis within the olfactory deutocerebrum of the crayfish Procambarus clarkii from hatchlings to adults. Using a proliferation marker and immunostaining, we found that throughout development each hemibrain contains a neurogenic complex consisting of five parts: two proliferation zones, each within the neuronal soma clusters containing local or projection interneurons, a tail of proliferating cells extending from each proliferation zone, and an elongated clump of cells where the two tails meet. The clump of cells comprises two subdivisions joined at a nucleus-free central area. Each subdivision consists of a dense group of clump cells with small, spindle-shaped nuclei and is connected to one of the proliferation zones by a strand of fibrous material encompassing the tail of proliferating cells extending from it. We identify one proliferating cell with a large nucleus in each subdivision as a putative neuroblast. Its daughter cells migrate through the strands to the associated proliferation zones, but in the strand leading to the soma cluster of local interneurons this is masked by local proliferation. We conclude that neurogenesis in the olfactory deutocerebrum of juvenile and adult P. clarkii is based on a few neuroblasts that are associated with unique clumps of cells likely representing stem cell niches.     

Cellular basis of taste reception

The recent application of precise biochemical and electrophysiological techniques to studies of taste cells has brought new insights into the cellular mechanisms of taste transduction. They have revealed that taste cells use a variety of mechanisms for transduction, including apically located ion channels, ligand-gated channels, and receptors coupled to second messenger systems.     

Structural basis for diversity of the EF-hand calcium-binding proteins

The calcium binding proteins of the EF-hand super-family are involved in the regulation of all aspects of cell function. These proteins exhibit a great diversity of composition, structure, Ca2+-binding and target interaction properties. Here, our current understanding of the Ca2+-binding mechanism is assessed. The structures of the EF-hand motifs containing 11-14 amino acid residues in the Ca2+-binding loop are analyzed within the framework of the recently proposed two-step Ca2+-binding mechanism. A hypothesis is put forward that in all EF-hand proteins the Ca2+-binding and the resultant conformational responses are governed by the central structure connecting the Ca2+-binding loops in the two-EF-hand domain. This structure, named EFbeta-scaffold, defines the position of the bound Ca2+, and coordinates the function of the N-terminal (variable and flexible) with the C-terminal (invariable and rigid) parts of the Ca2+-binding loop. It is proposed that the nature of the first ligand of the Ca2+-binding loop is an important determinant of the conformational change. Additional factors, including the interhelical contacts, the length, structure and flexibility of the linker connecting the EF-hand motifs, and the overall energy balance provide the fine-tuning of the Ca2+-induced conformational change in the EF-hand proteins.     

Cellular basis of graft-versus-host reactions

The biologic basis of Graft-Versus-Host Disease (GVHD) is presented as an extremely complex immunopathologic syndrome that involves interaction between many different donor and host cell types. A model of acute lethal GVHD was employed where adult unirradiated (DA X LEW)F1 rats were injected with LEW spleen and lymph node cells. Controls received the same dose of syngeneic cells. At intervals from 2 to 21 days after cell injection, GVHD and control animals were killed and nonadherent cell suspensions prepared from their lymph nodes, spleen and peripheral blood. Cell suspensions were treated with LEW-anti-DA-alloantiserum or normal LEW serum and then analyzed for sIgM+ (B cells), W 3/13+ (T cells), and IgG-Fc receptors (FcR). Evidence is discussed for the selective removal of host cells with the alloantiserum. In addition, the level of naturally cytolytic (NK/NC) cells was assessed by adding GVHD and control nonadherent lymphoid cells to heterologous lymphoma and sarcoma target cells. Evidence is presented that during acute GVHD, in this parental----F1 combination, there is an early increase within most compartments of donor as well as host W 3/13+ and W 3/13+FcR+ cells. NK/NC cells are increased as well at day 7. During middle stages of acute GVHD, host sIgM+ cells predominate. Late-stage acute GVHD rats contain few donor and host W 3/13+, W 3/13+FcR+, and NK/NC cells but many null cells most of which are FcR-. The importance of unraveling the nature of donor- and host-cell interactions occurring during acute GVHD, which result in rats whose lymphoid tissues are severely depleted of all nonadherent lymphoid cells but FcR- null cells, is discussed.     

Cellular basis for polarized light perception in the spider crab,Libinia

Summary Differential increases in the numbers of pinocytotic vesicles, multivesicular bodies and total complex bodies occurred in the cytoplasm of specific photoreceptor cells in the compound eye of the crab Libinia exposed for six hours to polarized light with various e-vector orientations. These data coupled with previous results on the same species proved that the seven retinular cells in each ommatidium formed two functional groups selectively light adaptable by e-vectors oriented 90° apart. One group (Channel I, comprising Cells 1, 4 and 5) was more affected by horizontal polarization; the other (Channel II, comprising Cells 2, 3, 6 and 7) was more affected by vertical polarization.This confirmed by a quite independent technique the conclusion reached from electrophysiological experiments on the crab Cardisoma that decapod compound eyes have two orthogonal polarization analyzer channels. In addition the present data showed that both channels occur in each ommatidium as hypothesized on previous electron microscopic evidence and that the axes of maximum absoprtion in the two retinal channels were parallel to the long axes of their cells' rhabdom microvilli, horizontal in Channel I and vertical in Channel II. The latter relations in turn supported the hypothesis that the dichroism of rhodopsin was fundamental to the analyzer mechanism.This research has been supported by U. S. Air Force Grant AFOSR 1064 and NASA Grant NGR 07-004-055. The authors wish to thank Professor Joseph G. Gall for generously sharing his electron microscope facilities.     

Morphological basis for the evolution of acoustic diversity in oscine songbirds

Acoustic properties of vocalizations arise through the interplay of neural control with the morphology and biomechanics of the sound generating organ, but in songbirds it is assumed that the main driver of acoustic diversity is variation in telencephalic motor control. Here we show, however, that variation in the composition of the vibrating tissues, the labia, underlies diversity in one acoustic parameter, fundamental frequency (F0) range. Lateral asymmetry and arrangement of fibrous proteins in the labia into distinct layers is correlated with expanded F0 range of species. The composition of the vibrating tissues thus represents an important morphological foundation for the generation of a broad F0 range, indicating that morphological specialization lays the foundation for the evolution of complex acoustic repertoires.     

Cellular and molecular constituents of olfactory sensation in vertebrates

Since the discovery of odorant-activated adenylate cyclase in the olfactory receptor cilia, research into the olfactory perception of vertebrates has rapidly expanded. Recent studies have shown how the odor discrimination starts at the receptor level: each of 700-1000 types of the olfactory neurons in the neural olfactory epithelium contains a single type of odor receptor protein. Although the receptors have relatively low specific affinities for odorants, excitation of different types of receptors forms an excitation pattern specific to each odorant in the glomerular layer of the olfactory bulb. It was demonstrated that adenosine 3',5'-cyclic monophosphate (cAMP) is very likely the sole second messenger for olfactory transduction. It was also demonstrated that the affinity of the cyclic nucleotide-gated channel for cAMP regulated by Ca(2+)/calmodulin is solely responsible for the adaptation of the cell. However, many other regulatory components were found in the transduction cascade. Regulated by Ca(2+) and/or the protein-phosphorylation, many of them may serve for the adaptation of the cell, probably on a longer time scale. It may be important to consider the resensitization as a part of this adaptation, as well as to collect kinetic data of each reaction to gain further insight into the olfactory mechanism.