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Early color-matching studies established that normal human color vision is trichromatic. Subsequent research revealed a causal link between trichromacy and the presence in the retina of three classes of cone photopigments. Over the years, measurements of the photopigment complements of other species have expanded greatly and these are frequently used to predict the dimensionality of an animal's color vision. This review provides an account of how the linkage between the number of active photopigments and the dimensions of human color vision developed, summarizes the various mechanisms that can impact photopigment spectra and number, and provides an across-species survey to examine cases where the photopigment link to the dimensionality of color vision has been claimed. The literature reveals numerous instances where the human model fails to account for the ways in which the visual systems of other animals exploit information obtained from the presence of multiple photopigments in support of their behavior., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Acinetobacter baumannii is an important cause of healthcare-associated infections, and is particularly problematic among patients who undergo organ transplantation. We describe a case of fulminant sepsis caused by carbapenem-resistant A. baumannii harboring the blaOXA-23 carbapenemase gene and belonging to international clone II. This isolate led to the death of a patient 6 days after simultaneous kidney-pancreas transplantation. Autopsy findings revealed acute mitral valve endocarditis, myocarditis, splenic and renal emboli, peritonitis, and pneumonia. This case highlights the severe nature of certain A. baumannii infections and the vulnerability of transplanted patients to the increasingly intractable "high-risk" clones of multidrug-resistant organisms., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The two principal theories of color vision that emerged in the nineteenth century offered alternative ideas about the nature of the biological mechanisms that underlie the percepts of color. One, the Young-Helmholtz theory, proposed that the visual system contained three component mechanisms whose individual activations were linked to the perception of three principal hues; the other, the Hering theory, assumed there were three underlying mechanisms, each comprising a linked opponency that supported contrasting and mutually exclusive color percepts. These competing conceptions remained effectively untested until the middle of the twentieth century when single-unit electrophysiology emerged as a tool allowing a direct examination of links between spectral stimulation of the eye and responses of individual cells in visual systems. This approach revealed that the visual systems of animals known to have color vision contain cells that respond in a spectrally-opponent manner, firing to some wavelengths of stimulation and inhibiting to others. The discovery of spectral opponency, and the research it stimulated, changed irrevocably our understanding of the biology of color vision.

All mammalian cone photopigments are derived from the operation of representatives from two opsin gene families (SWS1 and LWS in marsupial and eutherian mammals; SWS2 and LWS in monotremes), a process that produces cone pigments with respective peak sensitivities in the short and middle-to-long wavelengths. With the exception of a number of primate taxa, the modal pattern for mammals is to have two types of cone photopigment, one drawn from each of the gene families. In recent years, it has been discovered that the SWS1 opsin genes of a widely divergent collection of eutherian mammals have accumulated mutational changes that render them nonfunctional. This alteration reduces the retinal complements of these species to a single cone type, thus rendering ordinary color vision impossible. At present, several dozen species from five mammalian orders have been identified as falling into this category, but the total number of mammalian species that have lost short-wavelength cones in this way is certain to be much larger, perhaps reaching as high as 10% of all species. A number of circumstances that might be used to explain this widespread cone loss can be identified. Among these, the single consistent fact is that the species so affected are nocturnal or, if they are not technically nocturnal, they at least feature retinal organizations that are typically associated with that lifestyle. At the same time, however, there are many nocturnal mammals that retain functional short-wavelength cones. Nocturnality thus appears to set the stage for loss of functional SWS1 opsin genes in mammals, but it cannot be the sole circumstance.

Standard initial assessment via ultrasound of a 4-year-old girl with hypertension revealed the absence of one kidney. Instead of cross-sectional imaging of the retroperitoneal space, a functional (nuclear) study was performed. This revealed a malformed kidney within the chest. Though systemic levels of renin and aldosterone were not elevated, removal of the malformed kidney normalized the blood pressure. The presence of prominent smooth muscle nodules surrounding the arteries was seen in the malformed kidney. Initial attempts to avert surgery by pharmacologically reducing blood flow to the malformed kidney were unsuccessful. The review of the literature offers little evidence to support such a strategy.

Color vision is conventionally defined as the ability of animals to reliably discriminate among objects and lights based solely on differences in their spectral properties. Although the nature of color vision varies widely in different animals, a large majority of all vertebrate species possess some color vision and that fact attests to the adaptive importance this capacity holds as a tool for analyzing the environment. In recent years dramatic advances have been made in our understanding of the nature of vertebrate color vision and of the evolution of the biological mechanisms underlying this capacity. In this chapter I review and comment on these advances.

Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. β-Galactosidase staining in PRCP(gt/gt) mice reveals expression in kidney and vasculature. Invasive telemetric monitorings show that PRCP(gt/gt) mice have significantly elevated blood pressure. PRCP(gt/gt) mice demonstrate shorter carotid artery occlusion times in 2 models, and their plasmas have increased thrombin generation times. Pharmacologic inhibition of PRCP with Z-Pro-Prolinal or plasma kallikrein with soybean trypsin inhibitor, Pro-Phe-Arg-chloromethylketone or PKSI 527 also shortens carotid artery occlusion times. Aortic and renal tissues have uncoupled eNOS and increased reactive oxygen species (ROS) in PRCP(gt/gt) mice as detected by dihydroethidium or Amplex Red fluorescence or lucigenin luminescence. The importance of ROS is evidenced by the fact that treatment of PRCP(gt/gt) mice with antioxidants (mitoTEMPO, apocynin, Tempol) abrogates the hypertensive, prothrombotic phenotype. Mechanistically, our studies reveal that PRCP(gt/gt) aortas express reduced levels of Kruppel-like factors 2 and 4, thrombomodulin, and eNOS mRNA, suggesting endothelial cell dysfunction. Further, PRCP siRNA treatment of endothelial cells shows increased ROS and uncoupled eNOS and decreased protein C activation because of thrombomodulin inactivation. Collectively, our studies identify PRCP as a novel regulator of vascular ROS and homeostasis.

The color vision of most platyrrhine primates is determined by alleles at the polymorphic X-linked locus coding for the opsin responsible for the middle- to long-wavelength (M/L) cone photopigment. Females who are heterozygous at the locus have trichromatic vision, whereas homozygous females and all males are dichromatic. This study characterized the opsin alleles in a wild population of the socially monogamous platyrrhine monkey Callicebus brunneus (the brown titi monkey), a primate that an earlier study suggests may possess an unusual number of alleles at this locus and thus may be a subject of special interest in the study of primate color vision. Direct sequencing of regions of the M/L opsin gene using feces-, blood-, and saliva-derived DNA obtained from 14 individuals yielded evidence for the presence of three functionally distinct alleles, corresponding to the most common M/L photopigment variants inferred from a physiological study of cone spectral sensitivity in captive Callicebus., (© 2010 Wiley-Liss, Inc.)

There have been significant advances in our understanding of mammalian color vision over the past 15 years. This paper reviews a number of topics that have been central to these recent efforts, including: (1) the extent and nature of ultraviolet vision in mammals, (2) the evolutionary loss of short-wavelength-sensitive cones in some mammals, (3) the possible roles of rod signals in mammalian color vision, (4) the evolution of mammalian color vision, and (5) recent laboratory investigations of animal color vision. Successes in linking opsin genes and photopigments to color vision have been key to the progress made on each of these issues., (© 2010 The Author, Ophthalmic and Physiological Optics © 2010 The College of Optometrists.)

Only two of the four cone opsin gene families found in vertebrates are represented in contemporary eutherian and marsupial species. Recent genetic studies of two species of South American marsupial detected the presence of representatives from two of the classes of cone opsin genes and the structures of these genes predicted cone pigments with respective peaks in the ultraviolet and long-wavelength portions of the spectrum. The Virginia opossum (Didelphis virginiana), a profoundly nocturnal animal, is the only marsupial species found in North America. The prospects for cone-based vision in this species were examined through recordings of the electroretinogram (ERG), a commonly examined retinal response to photic stimulation. Recorded under flickering-light conditions that elicit signals from cone photoreceptors, the spectral sensitivity of the opossum eye is well accounted for by contributions from the presence of a single cone pigment having peak absorption at 561-562 nm. A series of additional experiments that employed various chromatic adaptation paradigms were conducted in a search for possible contributions from a second (short-wavelength sensitive) cone pigment. We found no evidence that such a mechanism contributes to the ERG in this marsupial.

Colour vision allows animals to reliably distinguish differences in the distributions of spectral energies reaching the eye. Although not universal, a capacity for colour vision is sufficiently widespread across the animal kingdom to provide prima facie evidence of its importance as a tool for analysing and interpreting the visual environment. The basic biological mechanisms on which vertebrate colour vision ultimately rests, the cone opsin genes and the photopigments they specify, are highly conserved. Within that constraint, however, the utilization of these basic elements varies in striking ways in that they appear, disappear and emerge in altered form during the course of evolution. These changes, along with other alterations in the visual system, have led to profound variations in the nature and salience of colour vision among the vertebrates. This article concerns the evolution of colour vision among the mammals, viewing that process in the context of relevant biological mechanisms, of variations in mammalian colour vision, and of the utility of colour vision.

Messenger RNAs, in addition to coding for proteins, may contain regulatory elements that affect how the protein is translated. These include protein and microRNA-binding sites. Transterm (http://mRNA.otago.ac.nz/Transterm.html) is a database of regions and elements that affect translation with two major unique components. The first is integrated results of analysis of general features that affect translation (initiation, elongation, termination) for species or strains in Genbank, processed through a standard pipeline. The second is curated descriptions of experimentally determined regulatory elements that function as translational control elements in mRNAs. Transterm focuses on protein binding sites, particularly those in 3'-untranslated regions (3'-UTR). For this release the interface has been extensively updated based on user feedback. The data is now accessible by strain rather than species, for example there are 10 Escherichia coli strains (genomes) analysed separately. In addition to providing a repository of data, the database also provides tools for users to query their own mRNA sequences. Users can search sequences for Transterm or user defined regulatory elements, including protein or miRNA targets. Transterm also provides a central core of links to related resources for complementary analyses.

Thirty years ago virtually everything known about primate color vision derived from psychophysical studies of normal and color-defective humans and from physiological investigations of the visual system of the macaque monkey, the most popular of human surrogates for this purpose. The years since have witnessed much progress toward the goal of understanding this remarkable feature of primate vision. Among many advances, investigations focused on naturally occurring variations in color vision in a wide range of nonhuman primate species have proven to be particularly valuable. Results from such studies have been central to our expanding understanding of the interrelationships between opsin genes, cone photopigments, neural organization, and color vision. This work is also yielding valuable insights into the evolution of color vision.

Studies of Syrian golden hamsters (Mesocricetus auratus) have yielded contradictory evidence as to whether the retina of this species supports a population of cones containing short-wavelength sensitive pigments. We undertook a re-examination of this issue by (a) measuring lens transmission, (b) determining complete spectral sensitivity functions using electroretinogram (ERG) flicker photometry, (c) employing a sensitive chromatic-adaptation paradigm in conjunction with ERG measurements to conduct a specific search for the presence of a short-wavelength sensitive mechanism, and (d) assaying for the presence of retinal mRNA using real-time, reverse transcription polymerase chain reactions (RT-PCR). Parallel measurements were made on Turkish hamster (Mesocricetus brandtii) and control measurements were derived from recordings made on a rodent whose retina is known to contain a population of short-wavelength sensitive cones (the rat, Rattus norvegicus). Although UV opsin transcripts can be detected in the retina of the Syrian hamster, the electrophysiological measurements imply that these are not translated. Syrian hamsters thus lack a functional short-wavelength sensitive pigment, and that seems also true for the Turkish hamster. Members of this genus belong to a disparate group of mammals that have lost function of their short-wavelength sensitive cone pigments through ancestral opsin gene mutations.

The dendritic patterning of retinal horizontal cells has been shown to be specified by the cone photoreceptor afferents. The present investigation has addressed whether this specification is due to visually dependent synaptic transmission in the outer plexiform layer or to some other early, pre-visual, neural activity. Individually labeled horizontal cells from dark-reared mice, as well as from mice carrying a mutation in the Cacna1f gene, which encodes the pore-forming calcium channel subunit Ca(v)1.4, were assessed for various morphological features. The dark-reared mice showed no alteration in any of these features, despite showing a compromised maximal voltage response in the electroretinograms. The retinas of Cacna1f mutant mice, by contrast, showed conspicuous morphological changes that mimicked the effects observed previously in coneless transgenic mice. These changes were present as early as postnatal day 10, when the shape and density of the cone pedicles appeared normal. Ultrastructurally, however, the pedicles at this early stage, as well as in maturity, lacked synaptic ribbons and the invaginations associated with postsynaptic processes. These results suggest a role for this calcium channel subunit in ribbon assembly in addition to its role in modulating calcium influx and glutamate release. Together, they suggest a complex cascade of interactions between developing cone pedicles and horizontal cell dendrites involving early spontaneous activity, dendritic attraction, ribbon assembly, and pedicle invagination., ((c) 2007 Wiley-Liss, Inc.)

The mouse retina contains two classes of cone photopigment with respective peak sensitivities in the middle (M) wavelengths and in the ultraviolet (UV) portion of the spectrum. To examine the functional roles subserved by the UV pigment, the absorption of light by the mouse lens was measured and voltage versus intensity (V-log I) functions were derived from recordings of the flicker ERG made under test conditions designed to maximize the relative sensitivities of the two pigment types. These V-log I data accurately predict ERG-based spectral sensitivity functions, but they fail to provide a similarly accurate account of behaviorally based measurements of spectral sensitivity in that the ERG spectral sensitivity function has much higher sensitivity in the UV wavelengths than does the behavioral spectral sensitivity function. The disparity between these two is argued to be a consequence of the widespread receptor co-expression of the two types of cone pigment in the mouse and of the pattern of retinal wiring that is thought to be characteristic of all mammalian retinas.

People often experience age-related declines in cone-based visual capacities despite an absence of apparent visual pathology. Although mice are used as models of human visual pathologies associated with aging, little is known about how age impacts vision in animals with disease-free retinas since most studies have heretofore examined relatively young mice. We examined the effects of age on cone-based vision by assessing opsin gene transcription, cone densities, the flicker electroretinogram (ERG), and behavioral increment thresholds in mice. ERG measurements of cone function showed age-related declines in maximum voltage (Vmax), while opsin gene transcription, cone density, and increment thresholds were unchanged even in extremely old mice. The age-related decline in Vmax seen in mice is qualitatively similar to that documented for human subjects. It is notable that Vmax, a commonly used index of ERG activity, does not predict behavioral performance in the mouse.

Aotus is a platyrrhine primate that has been classically considered to be nocturnal. Earlier research revealed that this animal lacks a color vision capacity because, unlike all other platyrrhine monkeys, Aotus has a defect in the opsin gene that is required to produce short-wavelength sensitive (S) cone photopigment. Consequently, Aotus retains only a single type of cone photopigment. Other mammals have since been found to show similar losses and it has often been speculated that such change is in some fashion tied to nocturnality. Although most species of Aotus are indeed nocturnal, recent observations show that Aotus azarai, an owl monkey species native to portions of Argentina and Paraguay, displays a cathemeral activity pattern being active during daylight hours as frequently as during nighttime hours. We have sequenced portions of the S-cone opsin gene in A. azarai and Aotus nancymaae, the latter a typically nocturnal species. The S-cone opsin genes in both species contain the same fatal defects earlier detected for Aotus trivirgatus. On the basis of the phylogenetic relationships of these three species these results imply that Aotus must have lost a capacity for color vision early in its history and they also suggest that the absence of color vision is not compulsively linked to a nocturnal lifestyle.

Changes in the genes encoding sensory receptor proteins are an essential step in the evolution of new sensory capacities. In primates, trichromatic color vision evolved after changes in X chromosome-linked photopigment genes. To model this process, we studied knock-in mice that expressed a human long-wavelength-sensitive (L) cone photopigment in the form of an X-linked polymorphism. Behavioral tests demonstrated that heterozygous females, whose retinas contained both native mouse pigments and human L pigment, showed enhanced long-wavelength sensitivity and acquired a new capacity for chromatic discrimination. An inherent plasticity in the mammalian visual system thus permits the emergence of a new dimension of sensory experience based solely on gene-driven changes in receptor organization.

X-linked photopigment polymorphism produces six different color vision phenotypes in most species of New World monkey. In the subfamily Callitrichinae, the three M/L alleles underlying these different phenotypes are present at unequal frequencies suggesting that selective pressures other than heterozygous-advantage operate on these alleles. Earlier we investigated this hypothesis with functional substitution, a technique using a computer monitor to simulate colors as they would appear to humans with monkey visual pigments (Visual Neuroscience 21:217-222, 2004). The stimuli were derived from measurements of ecologically relevant fruit and foliage. We found that discrimination performance depended on the relative spectral positioning of the substituted M and L pigment pair. Here we have undertaken a systematic examination of two simulation parameters--test field luminance and stimulus duration. Discriminability of the fruit colors depended on which phenotype was simulated but only at short stimulus durations and/or low luminances. Under such conditions, phenotypes with the larger pigment peak separations performed better. At longer durations and higher luminances, differences in performance across different substitutions tended to disappear. The stimuli used in this experiment were analyzed with several color discrimination models. There was limited agreement among the predictions made by these models regarding the capabilities of animals with different pigment pairs and none predicted the dependence of discrimination on changes in luminance and stimulus duration.

Rod and cone visual pigments of 11 marine carnivores were evaluated. Rod, middle/long-wavelength sensitive (M/L) cone, and short-wavelength sensitive (S) cone opsin (if present) sequences were obtained from retinal mRNA. Spectral sensitivity was inferred through evaluation of known spectral tuning residues. The rod pigments of all but one of the pinnipeds were similar to those of the sea otter, polar bear, and most other terrestrial carnivores with spectral peak sensitivities (lambda(max)) of 499 or 501 nm. Similarly, the M/L cone pigments of the pinnipeds, polar bear, and otter had inferred lambda(max) of 545 to 560 nm. Only the rod opsin sequence of the elephant seal had sensitivity characteristic of adaptation for vision in the marine environment, with an inferred lambda(max) of 487 nm. No evidence of S cones was found for any of the pinnipeds. The polar bear and otter had S cones with inferred lambda(max) of approximately 440 nm. Flicker-photometric ERG was additionally used to examine the in situ sensitivities of three species of pinniped. Despite the use of conditions previously shown to evoke cone responses in other mammals, no cone responses could be elicited from any of these pinnipeds. Rod photoreceptor responses for all three species were as predicted by the genetic data.

Platyrrhine monkeys typically have only a single X-chromosome opsin gene. Alleles of this gene code for multiple versions of middle- to long-wavelength cone photopigments. X-chromosome inactivation provides heterozygous females with a retinal mosaic of cones containing either of two types of M and L pigment, thus establishing the photopigment basis for trichromatic color vision. This study examined the proportions of L and M cones created by this process. For that purpose, electroretinogram flicker photometry was used to obtain complete spectral sensitivity functions from 60 heterozygous female monkeys drawn from seven genera of platyrrhine monkeys. To obtain estimates of cone proportions, these functions were subsequently fit with linear combinations of L and M cone fundamentals that were derived from similar recordings made on conspecific animals having only one type of M/L pigment. Consistent with a random X-chromosome inactivation process, the average L:M cone weighting across the sample was close to unity. At the same time, there were significant individual variations in L:M cone proportions. The genesis of this variation and its implications for seeing are discussed.

Transterm has now been publicly available for >10 years. Major changes have been made since its last description in this database issue in 2002. The current database provides data for key regions of mRNA sequences, a curated database of mRNA motifs and tools to allow users to investigate their own motifs or mRNA sequences. The key mRNA regions database is derived computationally from Genbank. It contains 3' and 5' flanking regions, the initiation and termination signal context and coding sequence for annotated CDS features from Genbank and RefSeq. The database is non-redundant, enabling summary files and statistics to be prepared for each species. Advances include providing extended search facilities, the database may now be searched by BLAST in addition to regular expressions (patterns) allowing users to search for motifs such as known miRNA sequences, and the inclusion of RefSeq data. The database contains >40 motifs or structural patterns important for translational control. In this release, patterns from UTRsite and Rfam are also incorporated with cross-referencing. Users may search their sequence data with Transterm or user-defined patterns. The system is accessible at http://uther.otago.ac.nz/Transterm.html.

Transgenic coneless mice were initially developed to study retinal function in the absence of cones. In coneless mice created by expressing an attenuated diphtheria toxin under the control of flanking sequences from the human L-cone opsin gene, a small number of cones (3-5% of the normal complement) survive in a retina that otherwise appears structurally quite normal. These cones predominantly ( approximately 87% of the total) contain UV-sensitive photopigment. ERG recordings, photoreceptor labeling, and behavioral measurements were conducted on coneless and wild-type mice to better understand how the nature of this alteration in receptor complement impacts vision. Signals from the small residual population of UV cones are readily detected in the flicker ERG where they yield signal amplitudes at saturation that are roughly proportional to the number of surviving cones. Behavioral measurements show that rod-based vision in coneless mice does not differ significantly from that of wild-type mice, nor does their rod system show any evidence of age-related deterioration. Coneless mice are able to make accurate rod-based visual discriminations at light levels well in excess of those required to reach cone threshold in wild-type mice.

Most New World (platyrrhine) monkeys have M/L cone photopigment polymorphisms that map directly into individual variations in visual sensitivity and color vision. We used electroretinogram flicker photometry to examine M/L cone photopigments in the New World monkey Callicebus moloch (the dusky Titi). Like other New World monkeys, this species has an M/L cone photopigment polymorphism that reflects the presence of X-chromosome opsin gene alleles. However, unlike other platyrrhines in which three M/L photopigments are typical, Callicebus has a total of five M/L cone photopigments. The peak sensitivity values for these pigments extend across the range from 530 to 562 nm. The result is an enhanced array of potential color vision phenotypes in this species.

Pocket gophers (Thomomys bottae) are rodents that spend much of their lives in near-lightless subterranean burrows. The visual adaptations associated with this extreme environment were investigated by making anatomical observations of retinal organization and by recording retinal responses to photic stimulation. The size of the eye is within the normal range for rodents, the lens transmits light well down into the ultraviolet, and the retina conforms to the normal mammalian plan. Electroretinogram recording revealed the presence of three types of photopigments, a rod pigment with a spectral peak of about 495 nm and two types of cone pigment with respective peak values of about 367 nm (UV) and 505 nm (medium-wavelength sensitive). Both in terms of responsivity to lights varying in temporal frequency and in response recovery following intense light adaptation, the cone responses of the pocket gopher are similar to those of other rodents. Labeling experiments indicate an abundance of cones that reach densities in excess of 30,000 mm-2. Cones containing UV opsin are found throughout the retina, but those containing medium-wavelength sensitive opsin are mostly restricted to the dorsal retina where coexpression of the two photopigments is apparently the rule. Rod densities are lower than those typical for nocturnal mammals.

Coffin-Lowry syndrome (CLS) is a rare but well-documented X-linked disorder characterized by small size, developmental delay/mental retardation, and characteristic facial and skeletal findings in affected males. The phenotype in affected females is far more variable and can include developmental differences, obesity, and characteristic facial and skeletal differences. Cardiac anomalies are reported in less than 20% of affected males, with cardiomyopathy being one of the rare but reported complications of this disorder. However, cardiomyopathy is not well characterized in CLS. Here, we report on a 14-year-old boy with physical and developmental findings consistent with CLS who presented with a relatively sudden onset of signs of congestive heart failure due to a restrictive cardiomyopathy; an endomyocardial biopsy demonstrated non-specific hypertrophic myocyte alterations consistent with cardiomyopathy. This is the first description of the histology and electron microscopy of cardiomyopathy in CLS., (Copyright 2004 Wiley-Liss, Inc.)

Recent years have witnessed a growing interest in learning how colour vision has evolved. This trend has been fuelled by an enhanced understanding of the nature and extent of colour vision among contemporary species, by a deeper understanding of the paleontological record and by the application of new tools from molecular biology. This review provides an assessment of the progress in understanding the evolution of vertebrate colour vision. In so doing, we offer accounts of the evolution of three classes of mechanism important for colour vision--photopigment opsins, oil droplets and retinal organisation--and then examine details of how colour vision has evolved among mammals and, more specifically, among primates.

Most platyrrhine monkeys have a triallelic M/L opsin gene polymorphism that underlies significant individual variations in color vision. A survey of the frequencies of these polymorphic genes suggests that the three alleles occur with equal frequency among squirrel monkeys (subfamily Cebinae), but are not equally frequent in a number of species from the subfamily Callitrichinae. This departure from equal frequency in the Callitrichids should slightly increase the ratio of dichromats to trichromats in the population and significantly alter the relative representation of the three possible dichromatic and trichromatic phenotypes. A particular feature of the inequality is that it leads to a relative increase in the number of trichromats whose M/L pigments have the largest possible spectral separation. To assess whether these trichromatic phenotypes are equally well equipped to make relevant visual discriminations, psychophysical experiments were run on human observers. A technique involving the functional substitution of photopigments was used to simulate the discrimination between fruits among a background of leaves. The goal of the simulation was to reproduce in the cones of human observers excitations equivalent to those produced in monkey cones as the animals view fruit. Three different viewing conditions were examined involving variations in the relative luminances of fruit and leaves and the spectrum of the illuminant. In all cases, performance was best for simulated trichromacies including M/L pigments with the largest spectral separation. Thus, the inequality of opsin gene frequency in Callitrichid monkeys may reflect adaptive pressures.

Purpose: Unraveling the mechanisms leading to clinically active calcium oxalate (CaOx) stone disease and the development of effective medical therapies to treat it have been hampered by the lack of appropriate animal models. To address this problem we developed a model of hyperoxaluria and calcium oxalate crystal deposition by implanting osmotic minipumps subcutaneously into male rats, that is minipump induced hyperoxaluria and crystal deposition in rats., Materials and Methods: Male Harlan-Sprague Dawley rats (225 to 290 gm) were implanted subcutaneously with 1-week 2 ml osmotic minipumps containing 1.5 M potassium oxalate (360 microM KOx/24 hours, [KOx-trt], 11) or phosphate buffered saline (PBS-trt, 9) on days 1 and 7. The 24-hour urine collections were performed on days 0, 4, 7, 11 and 14. Data were analyzed by ANOVA and Tukey's HSD. Urinary crystals were analyzed by light microscopy. Kidneys were harvested on day 14 and processed for light and polarizing microscopy, and RNA analysis.RESULTS Mean overall creatinine excretion +/- SEM (PBS-trt 107 +/- 7 and KOx-trt 123 +/- 6 microM/24 hours, p >0.07) and day 14 serum creatinine (PBS-trt 83 +/- 4 and KOx-trt 83 +/- 5 microM, p >or=0.9) were similar in the 2 treatment groups. Overall urinary volume (PBS-trt 11.3 +/- 0.8 and KOx-trt 18.0 +/- 1.5 ml/24 hours, p

The mouse retina contains both middle-wavelength-sensitive (M) and ultraviolet-sensitive (UV) photopigments that are coexpressed in cones. To examine some potential visual consequences of cone pigment coexpression, spectral sensitivity functions were measured in mice (Mus musculus) using both the flicker electroretinogram (ERG) and behavioral discrimination tests. Discrimination tests were also employed to search for the presence of color vision in the mouse. Spectral sensitivity functions for the mouse obtained from ERG measurements and from psychophysical tests each reveal contributions from two classes of cone having peak sensitivities (lambda(max)) of approximately 360 and 509-512 nm. The relative contributions of the two pigment types to spectral sensitivity differ significantly in the two types of measurements with a relationship reversed from that often seen in mammals. Mice were capable of discriminating between some pairs of spectral stimuli under test conditions where luminance-related cues were irrelevant. Since mice can make dichromatic color discriminations, their visual systems must be able to exploit differences in the spectral absorption properties among the cones. Complete selective segregation of opsins into individual photoreceptors is apparently not a prerequisite for color vision.

Among eutherian mammals, only primates possess trichromatic color vision. In Old World primates, trichromacy was made possible by a visual pigment gene duplication. In most New World primates, trichromacy is based on polymorphic variation in a single X-linked gene that produces, by random X inactivation, a patchy mosaic of spectrally distinct cone photoreceptors in heterozygous females. In the present work, we have modeled the latter strategy in a nonprimate by replacing the X-linked mouse green pigment gene with one encoding the human red pigment. In the mouse retina, the human red pigment seems to function normally, and heterozygous female mice express the human red and mouse green pigments at levels that vary between animals. Multielectrode array recordings from heterozygous female retinas reveal significant variation in the chromatic sensitivities of retinal ganglion cells. The data are consistent with a model in which these retinal ganglion cells draw their inputs indiscriminately from a coarse-grained mosaic of red and green cones. These observations support the ideas that (i) chromatic signals could arise from stochastic variation in inputs drawn nonselectively from red and green cones and (ii) tissue mosaicism due to X chromosome inactivation could be one mechanism for driving the evolution of CNS diversity.

Trichromatic color vision is routine among catarrhine primates, but occurs only as a variant form of color vision in some individuals in most platyrrhine genera. This arises from a fundamental difference in the organization of X-chromosome cone opsin genes in these two lineages: catarrhines have two opsin genes specifying middle- and long-wavelength-sensitive cone pigments, while platyrrhines have only a single gene. Some female platyrrhine monkeys achieve trichromacy because of a species polymorphism that allows the possibility of different opsin gene alleles on the two X-chromosomes. Recently, a similar opsin gene polymorphism was detected in some diurnal strepsirrhines, while at the same time appearing to be absent in any nocturnal genera. The aim of this study was to assess whether cone pigment polymorphism is inevitably linked to diurnality in strepsirrhines. Cone photopigments were measured in a species usually classified as diurnal, the ring-tailed lemur (Lemur catta), using electroretinogram flicker photometry, a noninvasive electrophysiological procedure. Each of 12 animals studied was found to have the same middle-wavelength cone pigment, with peak sensitivity at about 547 nm. In conjunction with earlier results, this implies that cone pigment polymorphism is unlikely to exist in this species and that, accordingly, such variation is not a consistently predictable feature of vision in diurnal strepsirrhines., (Copyright 2003 Wiley-Liss, Inc.)

The degu (Octodon degus) is a diurnal rodent, native to Chile. Basic features of vision and visual organization in this species were examined in a series of anatomical, electrophysiological and behavioral experiments. The lens of the degu eye selectively absorbs short-wavelength light and shows a progressive increase in optical density as a function of age. Electroretinograms recorded using a flicker-photometric procedure reveal three spectral mechanisms: a rod with peak sensitivity of about 500 nm and two types of cone having respective spectral peaks of about 362 nm and 507 nm. Opsin antibody labeling was used to determine the retinal distributions of the three receptor types. A total of about one-third of the approximately 9 million photoreceptors of the degu retina are cones with the two types (507 nm/362 nm) represented in a ratio of about 13:1. The contributions to vision of all three receptor types were examined in a series of behavioral experiments. A consistent feature of both the electrophysiological and behavioral results is that relatively high levels of light adaptation are required to effect the full transition from rod-based to cone-based vision. In behavioral tests degus were shown to be able to make color discriminations between ultraviolet and visible lights.

Previous research revealed significant individual variations in opsin genes and cone photopigments in several species of platyrrhine (New World) monkeys and showed that these in turn can yield significant variations in color vision. To extend the understanding of the nature of color vision in New World monkeys, electroretinogram flicker photometry was used to obtain spectral sensitivity measurements from representatives of four platyrrhine genera (Cebus, Leontopithecus, Saguinus, Pithecia). Animals from each genus were found to be polymorphic for middle to long-wavelength (M/L) sensitive cones. The presence of a short-wavelength sensitive photopigment was established as well so these animals conform to the earlier pattern in predicting that all male monkeys are dichromats while, depending on their opsin gene array, individual females can be either dichromatic or trichromatic. Across subjects a total of five different M/L cone pigments were inferred with a subset of three of these present in each species.

Purpose: To compare the morphologic and functional recovery of the retina after detachment and reattachment in an animal with a cone-dominant retina, the ground squirrel., Methods: Ground squirrel (Spermophilus beecheyi) retinas were detached for 1 day and reattached for 7, 35, or 96 days (n = 2, each time point). Flicker ERGs were recorded 1 day after the detachment and at various times after reattachment. Contrast-response functions were measured for isochromatic modulation and for selective modulation of short-wavelength-sensitive (S) and middle-wavelength-sensitive (M) cones. At the end of the experiment, retinas were prepared for light microscopy or immunocytochemical staining with antibodies to rod opsin, S and M cone opsins, cytochrome oxidase, synaptophysin, glial fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein (CRALBP), interphotoreceptor-binding protein (IRBP), and peanut agglutinin lectin (PNA). Photoreceptor density maps were created from wholemount preparations labeled with biotinylated PNA and anti-S cone opsin. Cell counts of photoreceptor nuclei and cone outer segments (OS) were compared with flicker ERG data. Cell death was examined by the TUNEL method., Results: Reattachment stopped photoreceptor cell death and reversed the disruption of interphotoreceptor matrix as well as the redistribution of Müller cell proteins. It also activated some astrocytes based on anti-GFAP staining. S- and M-cone OS showed a gradual recovery in length after reattachment, and this recovery continued to the longest time points examined. ERG contrast gains also recovered after reattachment, but these reached asymptotic levels by approximately a week after reattachment. There were significant correlations between outer nuclear layer (ONL) cell counts and ERG contrast gains. No differences were noted in the indices of recovery of M and S cones., Conclusions: The ERG can be used to follow specifically the changes in the retina that occur after retinal detachment and reattachment.

The spatial distributions of photoreceptors and retinal ganglion cells were examined in the spotted hyena (Crocuta crocuta). Two populations of cones were identified by immunocytochemical labeling. The hyena retina contains approximately 2.3 million middle- to long-wavelength sensitive (M/L) cones that reach peak densities of about 7,500/mm(2) in the vicinity of the optic nerve head. A sparser population of short-wavelength sensitive (S) cones, totaling about 0.3 million, was also detected. There is a striking disparity in the spatial distributions of the two cone types with S cones achieving peak density in a region located well below the optic nerve head. The differences in the spatial distributions of the two cone types have implications both for visual sensitivity and for color vision. Hyena rods outnumber cones by about 100:1 with rod density falling off modestly along a central-peripheral gradient. Ganglion cells were identified in retinal wholemounts by Nissl staining patterns. Their distribution defines a prominent visual streak with highest spatial packing (approx. 4,200/mm(2)) in an area centralis that is located in the temporal retina. The total number of ganglion cells is estimated at about 260,000. Using standard assumptions the maximum spatial resolution of the spotted hyena is calculated to be about 8.4 cycles/degree, a value similar to estimates obtained for other terrestrial carnivores., (Copyright 2003 S. Karger AG, Basel)

The spectral mechanisms of the ferret (Mustela putorious furo) were studied with electroretinogram (ERG) flicker photometry. Variations in adaptation state and flicker rate were used to define corneally based spectral sensitivities for the three classes of receptor present in the retina of this mustelid-rods (lambdamax = 505 nm), S cones (430 nm), and L cones (558 nm). The retinal distributions of the two classes of cone were determined using opsin antibody labeling. Ferret retinas contain a total of about 1.3 million cones with L cones outnumbering S cones in a ratio of approximately 14:1. ERGs were also recorded using 18.75-Hz flickering stimuli that were designed to isolate signals from individual cone classes. The contrast/response functions for signals originating from both S and L cones were linear over low-to-moderate levels of contrast, but with greatly different slopes for the two cone types. The L:S contrast gain ratio derived from a comparison of these slopes, as well as inferences drawn from another experiment in which responses to various combinations of L- and S-cone activation were analyzed, suggest that contributions of these two cone types to the flicker ERG have a relative weighting of about 4:1 to 5:1 (L/S).

A recent genetic investigation found some species of prosimian to have an opsin gene polymorphism [Nature 402 (1999) 36]. In the present study the functional implications of this finding were explored in a correlated investigation of opsin genes and spectral sensitivity measurements of a diurnal prosimian, Coquerel's sifaka (Propithecus verreauxi coquereli). Spectra recorded using electroretinogram (ERG) flicker photometry reveal a cone photopigment polymorphism paralleling an opsin gene polymorphism detected by molecular methods. This species has two middle-to-long-wavelength cone pigments with peak sensitivities of about 545 and 558 nm and a short-wavelength-sensitive cone with a peak at about 430 nm. The distribution of these pigments among animals predicts the presence of both dichromatic and trichromatic forms of color vision.

Transterm is a database that facilitates studies of translation and the translational control of protein synthesis. It contains a curated collection of elements in mRNAs that control translation, and biologically relevant mRNA regions extracted from GenBank. It is organised largely on a taxonomic basis with files and summaries for each species. Global patterns that may affect translation in particular species, for example bias in the context of initiation codons (Kozak's consensus or Shine-Dalgarno sequences) or termination codons, can be detected in the consensus and information content bias summaries. Several types of access are provided via a web browser interface. Transterm defined elements may be matched in a user's sequence or in the database. Alternatively, elements can be entered by the user to search specific sections of the database (for example, coding regions or 3' flanking regions or the 3'-UTRs) or the user's sequence. Each Transterm defined element has an associated biological description with references. The database is accessible at http://uther.otago.ac.nz/Transterm.html.

In people, retinal detachment often leads to a significant loss in cone-based vision. Most of the animal models commonly used for studying the consequences of retinal detachment have rod-dominated retinas. The purpose of this investigation was to evaluate the possibility that the ground squirrel, a rodent with a heavily cone-dominated retina, might provide a useful model for studying cone function in retinal detachment. Corneal ERGs were recorded from ground squirrels for large-field temporal modulations presented on a computer-controlled color monitor. Modulations were chosen to selectively stimulate either of the two classes of cone found in the ground squirrel retina. Under these test conditions, large and reliable cone ERGs could be readily recorded. In animals in which the retina had been surgically detached, the loss of cone signal was directly related to the number of cones in the detachment zone relative to the total cone population and that relationship did not differ for short-wavelength sensitive (S) and middle-wavelength sensitive (M) cones. Surgical reattachment produced a progressive recovery of cone-based signals. The ground squirrel seems likely to provide a useful animal model for studying the dynamics of cone function in retinal detachment and subsequent events.

Rats (Rattus norvegicus) have two classes of cone, one containing an ultraviolet (UV)-sensitive photopigment and the other housing a pigment maximally sensitive in the middle (M) wavelengths of the visible spectrum. The manner in which signals from these two cone types contribute to rat vision was investigated through recordings of a gross electrical potential (the electroretinogram, ERG) and behavioral discrimination tests. Spectral sensitivity functions obtained from both types of measurement indicate clear contributions from each of the cone classes, but there is a marked enhancement of the relative sensitivity to UV light in the behavioral index; for instance, under some photopic test conditions, rats are approximately equally sensitive to middle-wavelength and UV lights. In adaptation tests, thresholds for UV and M lights were found to be differentially elevated in the presence of chromatic adapting backgrounds, thus providing the possibility that signals from the two cones could be used by the rat visual system to support color discriminations. Evidence of dichromatic color vision in the rat was subsequently obtained from tests of wavelength discrimination.

Most New World monkeys have an X-chromosome opsin gene polymorphism that produces a variety of different colour vision phenotypes. Howler monkeys (Alouatta), one of the four genera in the family Atelidae lack this polymorphism. Instead, they have acquired uniform trichromatic colour vision similar to that of Old World monkeys, apes and people through opsin gene duplication. In order to determine whether closely related monkeys share this arrangement, spectral sensitivity functions that allow inferences about cone pigments were measured for 56 monkeys from two other Atelid genera, spider monkeys (Ateles) and woolly monkeys (Lagothrix). Unlike howler monkeys, both spider and woolly monkeys are polymorphic for their middle- and long-wavelength cone photopigments. However, they also differ from other polymorphic New World monkeys in having two rather than three possible types of middle- and long-wavelength cone pigments. This feature directly influences the relative numbers of dichromatic and trichromatic monkeys.

Introduction: Vesico-ureteric reflux (VUR), reflux of urine from the bladder into the ureter and towards the kidney, is an important cause of end-stage renal failure in both children and adults. Primary VUR is considered to be a result of a disruption of the normal anti-reflux mechanism of the ureterovesical junction (UVJ). VUR is common, occurring in approximately 1% to 2% of newborns in Caucasian populations. The aetiology of VUR is thought to involve a substantial genetic component, supported by the observation that VUR frequently occurs in multiple members of the same family. The purpose of this article is to review the literature supporting a genetic cause of VUR, and to draw together observations and make suggestions regarding differential diagnosis of VUR, which might help in future studies on the genetic aetiology of VUR., Results: A common theme arising was the notion that VUR may be caused by multiple genes in the population. However, any one individual with VUR may carry a single dominant mutant allele. Overall, progress has been made in mapping putative VUR loci in both humans and mice, although the mode(s) of inheritance and the exact nature of the underlying defect are still poorly understood., Conclusions: It is likely that over the next few years VUR genes will be mapped and, once identified, the challenge will be to understand how changes in the expression of these genes lead to the underlying defect in VUR.

Direct imaging of the retina by adaptive optics allows assessment of the relative number of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cones in living human eyes. We examine the functional consequences of variation in the relative numbers of L and M cones (L/M cone ratio) for two observers whose ratios were measured by direct imaging. The L/M cone ratio for the two observers varied considerably, taking on values of 1.15 and 3.79. Two sets of functional data were collected: spectral sensitivity measured with the flicker electroretinogram (ERG) and the wavelength of unique yellow. A genetic analysis was used to determine L and M cone spectra appropriate for each observer. Rayleigh matches confirmed the use of these spectra. We determined the relative strength of L and M cone contributions to ERG spectral sensitivity by fitting the data with a weighted sum of L and M cone spectra. The relative strengths so determined (1.06 and 3.38) were close to the cone ratios established by direct imaging. Thus variation in L/M cone ratio is preserved at the sites tapped by the flicker ERG. The wavelength of unique yellow varied only slightly between the two observers (576.8 and 574.7 nm). This small variation indicates that neural factors play an important role in stabilizing unique yellow against variation in the L/M cone ratio.

Transterm facilitates studies of messenger RNAs and translational control signals. Each messenger RNA (mRNA) from GenBank is extracted and broken into its functional components, its coding sequence, initiation context, termination context, flanking sequence representing its 5' UTR (untranslated region), 3' UTR and translational signals. In addition, numerical parameters characterising each coding region in Transterm, including codon and GC bias, are available. For each species in Transterm, the initiation and termination regions are aligned by their start or stop codons and presented as base frequency matrices and tables of the information content of the bases in the alignments. Users can obtain summaries of characteristics of the mRNAs for species of their choice and search for translational signals both in the Transterm database and in their own sequence. The current release contains data from over 10 000 species, including the complete genomes of 20 prokaryotes and three eukaryotes. Both flat-file and relational database forms of Transterm are accessible via the WWW at http://biochem.otago.ac.nz/Transterm/

Purpose: To develop methods for recording human electroretinogram (ERG) responses to stimuli that modulate different classes of cones in various ratios, to draw inferences about the combination of cone signal in early retinal processing., Methods: Subjects viewed large-field temporal modulations presented on a computer-controlled color monitor. A flicker photometric paradigm was used to equate the ERG response elicited by interleaved reference and test modulations. Test modulations were chosen to stimulate the L- and M-cones in various ratios. Results were obtained from color-normal subjects, dichromats, and an anomalous trichromat., Results: Reliable signals were obtained from all subjects to both L- and M-cone-isolating modulations and to intermediate modulations. Signals from color-defective subjects were predominantly determined by the modulation seen by only one cone type, whereas signals from color-normal subjects were sensitive to both L- and M-cone modulations. For most color-normal subjects, the recorded signal was a linear function of the contrasts seen by the L- and M-cones. There was individual variability in how strongly each cone type contributed to the overall signal., Conclusions: It is straightforward to record signals to color modulations presented on a CRT by using the flicker photometric ERG. For most observers, signals from L- and M-cones combine linearly. The relative contribution of the two cone classes varies across observers, probably because of individual differences in the relative numbers of L- and M-cones.