Stimulus-response function at several levels of background luminance, in the cat visual areas 17 and 18.

Stimulus-response curves of simple cells of the visual cortex were obtained by using 500-msec stationary stimuli. Background influence on single unit responses was studied. The contrast sensitivity of simple cells increases as a function of background luminance. The resolution power of these cortical cells for detecting differences in stimulus contrast decreases at background levels above 0.09 cd/m2.     

Intestinal epithelial barrier and mucosal immunity

The mucosal immune system acts as a first line of defense against bacterial and viral infections while also playing a crucial role in the establishment and maintenance of mucosal homeostasis between the host and the outside environment. In addition to epithelial cells and antigen-presenting cells (dendritic cells and macrophages), B and T lymphocytes form a dynamic mucosal network for the induction and regulation of secretory IgA (S-IgA) and cytotoxic T lymphocyte (CTL) responses. This review seeks to shed light on the pathways of induction and regulation of these responses and to elucidate the role they simultaneously play in fending off pathogen invasion and maintaining mucosal homeostasis.     

Stimulus-response function at several levels of background luminance,in the cat visual areas 17 and 18

Summary Stimulus-response curves of simple cells of the visual cortex were obtained by using 500-msec stationary stimuli. Background influence on single unit responses was studied. The contrast sensitivity of simple cells increases as a function of background luminance. The resolution power of these cortical cells for detecting differences in stimulus contrast decreases at background levels above 0.09 cd/m².This investigation was supported by a grant from the Consiglio Nazionale delle Ricerche, Rome (Italy).     

Melanopsin and inner retinal photoreception

Over the last ten years there has been growing acceptance that retinal photoreception among mammals extends beyond rods and cones to include a small number of intrinsically photosensitive retinal ganglion cells (ipRGCs). These ipRGCs are capable of responding to light in the absence of rod/cone input thanks to expression of an opsin photopigment called melanopsin. They are specialised for measuring ambient levels of light (irradiance) for a wide variety of so-called non-image-forming light responses. These include synchronisation of circadian clocks to light:dark cycles and the regulation of pupil size, sleep propensity and pineal melatonin production. Here, we provide a review of some of the landmark discoveries in this fast developing field, paying particular emphasis to recent findings and key areas for future investigation.     

Functional characterisation of naturally occurring mutations in human melanopsin

Melanopsin is a blue light-sensitive opsin photopigment involved in a range of non-image forming behaviours, including circadian photoentrainment and the pupil light response. Many naturally occurring genetic variants exist within the human melanopsin gene (OPN4), yet it remains unclear how these variants affect melanopsin protein function and downstream physiological responses to light. Here, we have used bioinformatic analysis and in vitro expression systems to determine the functional phenotypes of missense human OPN4 variants. From 1242 human OPN4 variants collated in the NCBI Short Genetic Variation database (dbSNP), we identified 96 that lead to non-synonymous amino acid substitutions. These 96 missense mutations were screened using sequence alignment and comparative approaches to select 16 potentially deleterious variants for functional characterisation using calcium imaging of melanopsin-driven light responses in HEK293T cells. We identify several previously uncharacterised OPN4 mutations with altered functional properties, including attenuated or abolished light responses, as well as variants demonstrating abnormal response kinetics. These data provide valuable insight into the structure–function relationships of human melanopsin, including several key functional residues of the melanopsin protein. The identification of melanopsin variants with significantly altered function may serve to detect individuals with disrupted melanopsin-based light perception, and potentially highlight those at increased risk of sleep disturbance, circadian dysfunction, and visual abnormalities.     

Biliverdin as an electron transfer catalyst for superoxide ion in aqueous medium

Stopped flow experiments gave evidence of the formation of a biliverdin-superoxide complex and/or a biliverdin radical anion by reaction of aqueous O2- with biliverdin. Such transient species are likely intermediates both in the bleaching of biliverdin, during exposure to the aerobic xanthine oxidase reaction, and in the reduction of ferricytochrome c under the same conditions.     

Survival of docetaxel-resistant prostate cancer cells in vitro depends on phenotype alterations and continuity of drug exposure

We evaluated in vitro the effect of paclitaxel and docetaxel on PC-3 and DU-145 prostate cancer cell lines to understand better the downstream events in drug-induced tumor cell death. Taxane treatments of DU-145 cells induced rapid cell death by apoptosis, but in PC-3 cells, treatments achieved growth arrest, followed by extensive karyokinesis resulting in multinucleation, giant-cell formation and delayed cell death. To determine if the giant multinucleated cells were able to produce proliferating and drug-resistant survivors, we first delineated the kinetics of drug activity and cytotoxic dose range. Analysis of both lines by colorimetric and cell viability assays demonstrated improved cytotoxicity of taxanes applied continuously. Selected doses and schedules of docetaxel were used to induce giant multinucleated cells that gave rise to docetaxel-resistant survivors, which remained sensitive to paclitaxel and other chemotherapeutics. Growth and morphology of the recovered clones was similar to parental cells. The resistant phenotype of these clones determined by immunofluorescence and immunoblot was associated with transient expression of the β-tubulin IV isoform and was independent of P-glycoprotein, bcl-2 and bcl-xL. Resistant clones will be useful to model progression of resistance to taxanes and to identify unknown and clinically important molecular mechanisms of cell death and resistance. Received 15 March 2002; received after revision 25 April 2002; accepted 27 May 2002     

The twin origins of renormalization group concepts

This paper traces the origin of renormalization group concepts back to two strands of 1950s high energy physics: the causal perturbation theory programme, which gave rise to the Stueckelberg-Petermann renormalization group, and the debate about the consistency of quantum electrodynamics, which gave rise to the Gell-Mann-Low renormalization group. Recognising the different motivations that shaped these early approaches sheds light on the formal and interpretive diversity we find in contemporary renormalization group methods.     

The emerging role for sphingolipids in the eukaryotic heat shock response

Eukaryotic cells have a highly conserved response to an increase in temperature, termed the heat shock response. Recent research has revealed multiple roles for various sphingolipids in the heat shock responses of both yeast and mammalian cells. Heat stressed or shocked yeast and mammalian cells have an acute activation of serine palmitoyltransferase, resulting in the de novo biosynthesis of sphingolipids. Also, both mammalian and yeast cells were shown to increase ceramide levels upon heat stress or shock. In yeast cells, several functions have emerged for the de novo produced sphingoid bases in terms of the heat stress response. These functions include a role in accumulation of trehalose, a role in the heat-induced transient G0/G1 cell cycle arrest and phytosphingosine activation of a ubiquitin protein degradation pathway. However, in mammalian systems, ceramides have been demonstrated as bioactive lipids. Ceramides produced in response to heat shock were demonstrated to induce the production of c-jun, leading to apoptosis, and to be upstream of dephosphorylation of serine-rich proteins. Increasingly, sphingolipids are emerging as bioactive signaling molecules involved in numerous aspects of the eukaryotic heat shock response.     

Cyclosporine resistant effector cells in rabbit skin allografts

Histoincompatible skin grafts in rabbits treated with cyclosporine can permanently engraft but show a transient mononuclear cellular infiltrate. This transient cyclosporine-resistant infiltrate consists of cells which are sensitive to steroids, radiation and cryopreservation. They have the same ACM-1 phenotype and the same characteristics as cyclosporine-sensitive cells.     

Biliverdin as an electron transfer catalyst for superoxide ion in aqueous medium

Summary Stopped flow experiments gave evidence of the formation of a biliverdin-superoxide complex and/or a biliverdin radical anion by reaction of aqueous O₂ ^– with biliverdin. Such transient species are likely intermediates both in the bleaching of biliverdin, during exposure to the aerobic xanthine oxidase reaction, and in the reduction of ferricytochromec under the same conditions.     

Cyclosporine resistant effector cells in rabbit skin allografts

Summary Histoincompatible skin grafts in rabbits treated with cyclosporine can permanently engraft but show a transient mononuclear cellular infiltrate. This transient cyclosporine-resistant infiltrate consists of cells which are sensitive to steroids, radiation and cryopreservation. They have the same ACM-1 phenotype and the same characteristics as cyclosporine-sensitive cells.9 January 1987Supported by the Swiss National Research Foundation, Grant No. 3.908-0.83.     

Plasma, testicular, and adrenal cortex levels of androgens in the perinatal period and determination of neonatal hypertestosteronemia in guinea pigs]

The perinatal period is characterized in the male faetus and new-born Guinea-Pig by a prenatal increase in testis testosterone and by a neonatal peak in plasma testosterone. This transient rise in plasma testosterone is testis dependent and light dependent at birth.     

Radial skeletal dissolution to promote vegetative reproduction in a solitary coralDiaseris distorta

The solitary, free-living coralDiaseris distorta (Michelin) (Fungiidae, Scleractinia) reproduces asexually by fragmentation along radially oriented slits. Localized skeletal dissolution, which can be recognized as white, opaque and chalky lines along the thecal wall between segments, ultimately results in autotomy. We suggest that the skeletal dissolution which dissolves the weakest part of the corallum for easy breakage, is a species-specific character.     

Slice cultures of cerebellar,hippocampal and hypothalamic tissue

Summary Cerebellar, hippocampal and hypothalamic slices prepared from newborn and 7-day-old rats were cultured by means of the roller-tube technique. Identification of cells was made easier by the fact that at least part of the characteristic cytoarchitecture of the tissue was preserved in vitro. Cerebellar Purkinje cells and neurones of the deep cerebellar nuclei were recognized on the basis of their size, their location within the culture and their dendritic arborization. Pyramidal cells of all hippocampal subfields displayed their characteristic basal and apical dendritic trees with numerous spinous processes. Hippocampal granule cells gave rise to a monopolar dendritic arbor; their axons terminated in the dentate hilus and CA3 region. Golgi-like immuniperoxidase staining allowed localization of groups of neurophysin-positive neurones in slices prepared from the anterior hypothalamus. These neurones, bilaterally bordering the third ventricle, usually displayed a simple dendritic arborization and fine beaded axons.—Cultivation of brain slices prepared from young rats offers particular advantages in that the cultured cells are organized in an organotypic monolayer and individual living neurones may be directly visualized.Acknowledgments. I would like to thank Dr J. Zimmer and Dr M. Sofroniew for their valuable help with the Timms and immunoperoxidase staining techniques and Mr R. Schlichter and L. Wohlfart for illustrating the culture procedure. The excellent technical assistance of Ms L. Rietschin and E. Hoffmann is gratefully acknowledged.     

The functions of mucosal T cells in containing the indigenous commensal flora of the intestine

There is an immense load of non-pathogenic commensal bacteria in the distal small intestine and the colon of mammals. The physical barrier that prevents penetration (translocation) of these organisms into the body is a simple epithelium comprised of the single enterocyte/colonocyte cell layer with its overlying mucus. In this review, we discuss the roles of intestinal T cells in initiating and regulating innate and adaptive mucosal immune responses of the mucosal immune system that avoid or limit penetration of the commensal intestinal bacteria. Received 9 August 2002; accepted 9 September 2002 RID="*" ID="*"Corresponding author.     

Sensitivity and response kinetics alter during suppression-recovery in cone photoreceptors

Threshold and response amplitude of cone photoreceptors were measured during progression from flicker-induced suppression to recovery. Increases in sensitivity closely paralleled increases in amplitude. Recovered responses exhibited faster kinetics than suppressed responses. The idea that recovery from suppression is a manifestation of the shift in the stimulus-response relationship which occurs with light adaptation is supported.     

Real-time models of morphogenetic processes

Morphological transformations are often describable by simple series kinetic models, A----B, A----B----C, etc., which allow assessment of the rates of interconversion of the distinguishable shapes or forms present and their probabilities of occurrence at various points in time, thus providing a means for kinetic comparisons with biochemical measurements of the molecular-level reactions that cause the transformations. When changes in cell morphology are followed turbidimetrically, the real-time progress curves can be simulated by fitting the data to a form of Beer's law for scattering by mixtures in which the species concentrations change with time in accordance with the chosen kinetic scheme. Because many even relatively large cells are mostly water, classical light scattering theory can be used to interpret the turbidimetric data in terms of simple geometrical models of average cell size and shape suggested by microscopic examination. Two examples are briefly considered, the stimulus-induced changes in blood platelet shape and apparent size and their correlation with cytosolic-free calcium, and apparent swimming motion exhibited by neutrophils in suspension.