Knockout of Nr2e3 prevents rod photoreceptor differentiation and leads to selective L-/M-cone photoreceptor degeneration in zebrafish

Mutations in the photoreceptor cell-specific nuclear receptor gene Nr2e3 increased the number of S-cone photoreceptors in human and murine retinas and led to retinal degeneration that involved photoreceptor and non-photoreceptor cells. The mechanisms underlying these complex phenotypes remain unclear. In the hope of understanding the precise role of Nr2e3 in photoreceptor cell fate determination and differentiation, we generated a line of Nr2e3 knockout zebrafish using CRISPR technology. In these Nr2e3-null animals, rod precursors undergo terminal mitoses but fail to differentiate as rods. Rod-specific genes are not expressed and the outer segment (OS) fails to form. Formation and differentiation of cone photoreceptors is normal. Specifically, there is no increase in the number of UV-cone or S-cone photoreceptors. Laminated retinal structure is maintained. After normal development, L-/M-cones selectively degenerate, with progressive shortening of OS that starts at age 1 month. The amount of cone phototransduction proteins is concomitantly reduced, whereas UV- and S-cones have normal OS lengths even at age 10 months. In vitro studies show Nr2e3 synergizes with Crx and Nrl to enhance rhodopsin gene expression. Nr2e3 does not affect cone opsin expression. Our results extend the knowledge of Nr2e3's roles and have specific implications for the interpretation of the phenotypes observed in human and murine retinas. Furthermore, our model may offer new opportunities in finding treatments for enhanced S-cone syndrome (ESCS) and other retinal degenerative diseases.     

Glutamine synthetase in cultured whole retinas from the embryonic chick. Role of protein and RNA syntheses in 4 degrees C storage enhancement

Glutamine synthetase (GS) activity is enhanced in cultured whole retinas when a 72 h incubation at 37 degrees C is preceded by storage at 4 degrees C for 2-24 h. This enhancement occurs even in the absence of glucocorticoids and is maximal in retinas from 11 to 14 d embryos. In comparison, cortisol-induced increases in retinal GS activity at 37 degrees C are optimal in retinas from 8 to 12 d embryos. This study, using cycloheximide (an inhibitor of protein synthesis) and cordycepin (an inhibitor of RNA synthesis), indicates that both protein and RNA synthesis are required for the 4 degrees C storage enhancement of GS activity. The necessary RNA synthesis occurs within the first 48 h following transfer to 37 degrees C and does not require concomitant protein synthesis. Uridine uptake, but not incorporation into trichloroacetic acid-precipitable material, is increased by initial 4 degrees C storage when compared with whole retina controls incubated at 37 degrees C for the total time. In contrast, both uptake and incorporation of amino acids are increased in 4 degrees C-stored retinas for as long as 72 h subsequent to transfer from 4 to 37 degrees C. This suggests that enhancement GS activity may arise from a combination of elevated general protein synthesis and specific messenger-RNA synthesis following 4 degrees C storage.     

The opportunity to be misled in studies of sexual selection

It is a challenge to measure sexual selection because both stochastic events (chance) and deterministic factors (selection) generate variation in individuals' reproductive success. Most researchers realize that random events ('noise') make it difficult to detect a relationship between a trait and mating success (i.e. the presence of sexual selection). There is, however, less appreciation of the dangers that arise if stochastic events vary systematically. Systematic variation makes variance-based approaches to measuring the role of selection problematic. This is why measuring the opportunity for sexual selection (I(s) and I(mates)) is so vulnerable to misinterpretation. Although I(s) does not measure actual sexual selection (because it includes stochastic variation in mating/fertilization success) it is often implicitly assumed that it will be correlated with the actual strength of sexual selection. The hidden assumption is that random noise is randomly distributed across populations, species or the sexes. Here we present a simple numerical example showing why this practice is worrisome. Specifically, we show that chance variation in mating success is higher when there are fewer potential mates per individual of the focal sex [i.e. when the operational sex ratio (OSR), is more biased]. This will lead to the OSR covarying with I(s) even when the strength of sexual selection is unaffected by the OSR. This can generate false confidence in identifying factors that determine variation in the strength of sexual selection. We emphasize that in nature, even when sexual selection is strong, chance variation in mating success is still inevitable because the number of mates per individual is a discrete number. We hope that our worked example will clarify a recent debate about how best to measure sexual selection.     

Variation in the strength of inbreeding depression across environments: Effects of stress and density dependence

In what types of environments should we expect to find strong inbreeding depression? Previous studies indicate that inbreeding depression, δ, is positively correlated with the stressfulness of the environment in which it is measured. However, it remains unclear why stress, per se, should increase δ. To our knowledge, only “competitive stress” has a logical connection to δ. Through competition for resources, better quality (outbred) individuals make the environment worse for lower quality (inbred) individuals, accentuating the differences between them. For this reason, we expect inbreeding depression to be stronger in environments where the fitness of individuals is more sensitive to the presence of conspecifics (i.e., where fitness is more density dependent). Indeed, some studies suggest a role for competition within environments, but this idea has not been tested in the context of understanding variation in δ across environments. Using Drosophila melanogaster, we estimated δ for viability in 22 different environments. These environments were simultaneously characterized for (1) stressfulness and (2) density dependence. Although stress and density dependence are moderately correlated with each other, inbreeding depression is much more strongly correlated with density dependence. These results suggest that mean selection across the genome is stronger in environments where competition is intense, rather than in environments that are stressful for other reasons.     

Transducer and base compliance alter the in situ 6 dof force measured from muscle during an isometric contraction in a multi-joint limb

Although musculoskeletal models are commonly used, validating the muscle actions predicted by such models is often difficult. In situ isometric measurements are a possible solution. The base of the skeleton is immobilized and the endpoint of the limb is rigidly attached to a 6-axis force transducer. Individual muscles are stimulated and the resulting forces and moments recorded. Such analyses generally assume idealized conditions. In this study we have developed an analysis taking into account the compliances due to imperfect fixation of the skeleton, imperfect attachment of the force transducer, and extra degrees of freedom (dof) in the joints that sometimes become necessary in fixed end contractions. We use simulations of the rat hindlimb to illustrate the consequences of such compliances. We show that when the limb is overconstrained, i.e., when there are fewer dof within the limb than are restrained by the skeletal fixation, the compliances of the skeletal fixation and of the transducer attachment can significantly affect measured forces and moments. When the limb dofs and restrained dofs are matched, however, the measured forces and moments are independent of these compliances. We also show that this framework can be used to model limb dofs, so that rather than simply omitting dofs in which a limb does not move (e.g., abduction at the knee), the limited motion of the limb in these dofs can be more realistically modeled as a very low compliance. Finally, we discuss the practical implications of these results to experimental measurements of muscle actions.     

Neural Plasticity and Consciousness

We introduce a distinction between cortical dominance andcortical deference, and apply it to various examples ofneural plasticity in which input is rerouted intermodally orintramodally to nonstandard cortical targets. In some cases butnot others, cortical activity `defers' to the nonstandard sourcesof input. We ask why, consider some possible explanations, andpropose a dynamic sensorimotor hypothesis. We believe that thisdistinction is important and worthy of further study, bothphilosophical and empirical, whether or not our hypothesis turnsout to be correct. In particular, the question of how the distinction should be explained is linked to explanatory gapissues for consciousness. Comparative and absolute explanatorygaps should be distinguished: why does neural activity in aparticular area of cortex have this qualitative expressionrather than that, and why does it have any qualitativeexpression at all? We use the dominance/deference distinction toaddress the comparative gaps, both intermodal and intramodal (notthe absolute gap). We do so not by inward scrutiny but rather by expanding our gaze to include relations between brain, body andenvironment.     

Suppressed patterns alter vision during binocular rivalry

Binocular rivalry occurs when incongruent patterns are presented to corresponding regions of the retinas, leading to fluctuations of awareness between the patterns . One attribute of a stimulus may rival whereas another may combine between the eyes , but it is typically assumed that the dominant features are perceived veridically. Here, we show this is not necessarily the case and that a suppressed visual feature can alter dominant perception. The cortical representations of oriented gratings can interact even when one of them is perceptually suppressed, such that the perceived orientation of the dominant grating is systematically biased depending on the orientation of the suppressed grating. A suppressed inducing pattern has the same qualitative effect as a visible one, but suppression reduces effective contrast by a factor of around six. A simple neural model quantifies and helps explain these illusions. These results demonstrate that binocular rivalry suppression operates in a graded fashion across multiple sites in the visual hierarchy rather than truncating processing at a single site and that suppressed visual information can alter dominant vision in real-time.     

A meta-analysis of crop pest and natural enemy response to landscape complexity

Many studies in recent years have investigated the relationship between landscape complexity and pests, natural enemies and/or pest control. However, no quantitative synthesis of this literature beyond simple vote-count methods yet exists. We conducted a meta-analysis of 46 landscape-level studies, and found that natural enemies have a strong positive response to landscape complexity. Generalist enemies show consistent positive responses to landscape complexity across all scales measured, while specialist enemies respond more strongly to landscape complexity at smaller scales. Generalist enemy response to natural habitat also tends to occur at larger spatial scales than for specialist enemies, suggesting that land management strategies to enhance natural pest control should differ depending on whether the dominant enemies are generalists or specialists. The positive response of natural enemies does not necessarily translate into pest control, since pest abundances show no significant response to landscape complexity. Very few landscape-scale studies have estimated enemy impact on pest populations, however, limiting our understanding of the effects of landscape on pest control. We suggest focusing future research efforts on measuring population dynamics rather than static counts to better characterise the relationship between landscape complexity and pest control services from natural enemies.     

Sex-biased dispersal in a rare butterfly and the implications for its conservation

The survival of many species may be dependent on their ability to exist in human-altered landscapes within metapopulations; in turn, metapopulation persistence is dictated by the ability of individuals to move effectively among patches to promote recolonization. The Taylor’s checkerspot butterfly (Euphydryas editha taylori) is a species that does not naturally occur in fragmented landscapes, yet it is now restricted to a handful of small isolated prairie habitats. Current recovery plans aim to establish a stable metapopulation; however, to date little is known about the species’ ability to move across the landscape. In 2010 and 2011, we conducted marking, tracking and boundary surveys to explore the movement dynamics of adults within two sites in Oregon, USA. Over the survey period, we marked 136 male butterflies, tracked 174 individuals and observed the behavior of 1,576 individual butterflies at site boundaries. Our study revealed a significant sex-bias in the movement dynamics of the Taylor’s checkerspot in both suitable habitat and surrounding matrix. Males were highly motile, whereas females appeared sedentary, rarely moving from their natal site. The limited dispersal behavior of females indicates that populations cannot persist naturally in a metapopulation and thus are at high risk of extinction. Based on our findings, we recommend that managers take proactive measures to increase or enable dispersal (including translocation) to existing and/or restored sites.     

人的体视超视锐度阈值

体视超视(?)象是视觉系统中(?)度的超(?)在一些特殊的(?)图形下,它的阈值可达2秒以下.考虑到人眼的一般体(?)锐度的60(?),(?)未超视度现象就是一个很有意义并值得注意研究的问题.对于如此精细的分辨能力,视(?)膜细胞可以说是很粗糙的(其直径约24秒)我们想了解,这么粗糙的视网膜是如何分辨出仅为其直径1/10的目标位差的呢?本文对人眼体视超视锐度现象做了一此研究,测定出体视超视锐度(?)值,并研究了低通滤波后对其影响.     

Lack of support for Rensch's rule in an intraspecific test using red flour beetle (Tribolium castaneum) populations

Rensch's rule proposes a universal allometric scaling phenomenon across species where sexual size dimorphism (SSD) has evolved: in taxa with male‐biased dimorphism, degree of SSD should increase with overall body size, and in taxa with female‐biased dimorphism, degree of SSD should decrease with increasing average body size. Rensch's rule appears to hold widely across taxa where SSD is male‐biased, but not consistently when SSD is female‐biased. Furthermore, studies addressing this question within species are rare, so it remains unclear whether this rule applies at the intraspecific level. We assess body size and SSD within Tribolium castaneum (Herbst), a species where females are larger than males, using 21 populations derived from separate locations across the world, and maintained in isolated laboratory culture for at least 20 years. Body size, and hence SSD patterns, are highly susceptible to variations in temperature, diet quality and other environmental factors. Crucially, here we nullify interference of such confounds as all populations were maintained under identical conditions (similar densities, standard diet and exposed to identical temperature, relative humidity and photoperiod). We measured thirty beetles of each sex for all populations, and found body size variation across populations, and (as expected) female‐biased SSD in all populations. We test whether Rensch's rule holds for our populations, but find isometry, i.e. no allometry for SSD. Our results thus show that Rensch's rule does not hold across populations within this species. Our intraspecific test matches previous interspecific studies showing that Rensch's rule fails in species with female‐biased SSD.     

Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans

The Drosophila transforming growth factor beta (TGF-beta) homolog Decapentaplegic (Dpp) acts as a morphogen that forms a long-range concentration gradient to direct the anteroposterior patterning of the wing. Both planar transcytosis initiated by Dynamin-mediated endocytosis and extracellular diffusion have been proposed for Dpp movement across cells. In this work, we found that Dpp is mainly extracellular, and its extracellular gradient coincides with its activity gradient. We demonstrate that a blockage of endocytosis by the dynamin mutant shibire does not block Dpp movement but rather inhibits Dpp signal transduction, suggesting that endocytosis is not essential for Dpp movement but is involved in Dpp signaling. Furthermore, we show that Dpp fails to move across cells mutant for dally and dally-like (dly), two Drosophila glypican members of heparin sulfate proteoglycan (HSPG). Our results support a model in which Dpp moves along the cell surface by restricted extracellular diffusion involving the glypicans Dally and Dly.     

The prisoner reentry industry

The Prisoner Reentry Industry found its beginnings in the recognition that men and women who were being released from prison continued to need assistance in their transition process. Depending upon the individual needs of each person, this determined the extent of what type of assistance needed. Within a short period of time it was determined that the greatest assistance was needed in the area of housing and employment. However, once a person completed this transition phrase that was usually understood to be about three years, the following questions arise: when does the reentry phase end? When does society allow the ex-offender to move on with their lives? Even when secure employment has been maintained, when other areas of the individuals’ life are functioning “at least like everyone else in society”, when does the reentry stop and the ex-offender allowed to enter into mainline society? This article attempts to show that we have not done a good job of allowing the ex-offender to move from the phase of prisoner reentry to the phase of contributor in our society.     

Markovian and non-Markovian protein sequence evolution: aggregated Markov process models

Over the years, there have been claims that evolution proceeds according to systematically different processes over different timescales and that protein evolution behaves in a non-Markovian manner. On the other hand, Markov models are fundamental to many applications in evolutionary studies. Apparent non-Markovian or time-dependent behavior has been attributed to influence of the genetic code at short timescales and dominance of physicochemical properties of the amino acids at long timescales. However, any long time period is simply the accumulation of many short time periods, and it remains unclear why evolution should appear to act systematically differently across the range of timescales studied. We show that the observed time-dependent behavior can be explained qualitatively by modeling protein sequence evolution as an aggregated Markov process (AMP): a time-homogeneous Markovian substitution model observed only at the level of the amino acids encoded by the protein-coding DNA sequence. The study of AMPs sheds new light on the relationship between amino acid-level and codon-level models of sequence evolution, and our results suggest that protein evolution should be modeled at the codon level rather than using amino acid substitution models.     

Do alien plants on Mediterranean islands tend to invade different niches from native species?

In order to understand invasions, it is important to know how alien species exploit opportunities in unfamiliar ecosystems. For example, are aliens concentrated in niches under-exploited by native communities, or widely distributed across the ecological spectrum? To explore this question, we compared the niches occupied by 394 naturalized alien plants with a representative sample from the native flora of Mediterranean islands. When niche structure was described by a functional group categorization, the distribution of native and alien species was remarkably similar, although “succulent shrubs” and “trees with specialized animal pollination mechanisms” were under-represented in the native species pool. When niche structure was described by Grime’s CSR strategy, the positioning of aliens and natives differed more strongly. Stress-tolerance was much rarer amongst the aliens, and a competitive strategy was more prevalent at the habitat level. This pattern is similar to previous findings in temperate Europe, although in those regions it closely reflects patterns of native diversity. Stressed environments are much more dominant in the Mediterranean. We discuss a number of factors which may contribute to this difference, e.g., competitive and ruderal niches are often associated with anthropogenic habitats, and their high invasibility may be due partly to introduction patterns rather than to a greater efficiency of aliens at exploiting them. Thus far, the reasons for invasion success amongst introduced species have proved difficult to unravel. Despite some differences, our evidence suggests that alien species naturalize across a wide range of niches. Given that their ecologies therefore vary greatly, one may ask why such species should be expected to share predictable traits at all?     

Categorial compositionality II: universal constructions and a general theory of (quasi-)systematicity in human cognition

A complete theory of cognitive architecture (i.e., the basic processes and modes of composition that together constitute cognitive behaviour) must explain the systematicity property--why our cognitive capacities are organized into particular groups of capacities, rather than some other, arbitrary collection. The classical account supposes: (1) syntactically compositional representations; and (2) processes that are sensitive to--compatible with--their structure. Classical compositionality, however, does not explain why these two components must be compatible; they are only compatible by the ad hoc assumption (convention) of employing the same mode of (concatenative) compositionality (e.g., prefix/postfix, where a relation symbol is always prepended/appended to the symbols for the related entities). Architectures employing mixed modes do not support systematicity. Recently, we proposed an alternative explanation without ad hoc assumptions, using category theory. Here, we extend our explanation to domains that are quasi-systematic (e.g., aspects of most languages), where the domain includes some but not all possible combinations of constituents. The central category-theoretic construct is an adjunction involving pullbacks, where the primary focus is on the relationship between processes modelled as functors, rather than the representations. A functor is a structure-preserving map (or construction, for our purposes). An adjunction guarantees that the only pairings of functors are the systematic ones. Thus, (quasi-)systematicity is a necessary consequence of a categorial cognitive architecture whose basic processes are functors that participate in adjunctions.     

The rate of rhodopsin phosphorylation in isolated rentinas of frog and cattle.

Phosphorylation of rhodopsin has been measured in isolated retinas incubated with 32P-phosphate under physiological conditions. The half-time of the light-induced phosphorylation was found to be approximately 2 min with frog retinas at 21 degrees C, and in the order of 1--2 min with cattle retinas at 36 degrees C. It is suggested by this slow rate that the phosphorylation reaction is not directly involved in the chain of events which lead from absorption of a photon to excitation of the photoreceptor cells but may perhaps have a regulatory function in controlling light/dark adaptation.     

Light-dependent binding of G-protein to outer segment membranes of toad photoreceptors [published erratum appears in J Gen Physiol 1987 May;89(5):following 837]

Light-dependent changes in the binding of G-protein were analyzed in outer segment disk membranes obtained from photoreceptors of the toad (Bufo marinus) retina. Isolated, intact retinas, incubated in oxygenated Ringer's solution at 23 +/- 1 degree C, were subjected to various conditions of illumination and then incubated in darkness for specified periods. The retinas were then chilled (0-4 degrees C) and the receptor outer segments (ROS) were isolated. Binding of the alpha- and beta-subunits of G-protein to the ROS membranes was analyzed by quantitating G alpha and G beta extracted from the membranes with hypotonic medium lacking GTP vs. hypotonic medium containing GTP (H and HG extracts, respectively). For retinas illuminated and then immediately chilled for analysis, the extent of G binding (relative abundance of G alpha, beta in the HG extract) increased with the extent of bleaching of the visual pigment. Near-maximal binding was observed after bleaches of greater than or equal to 30%. With an increasing period of incubation in darkness after approximately 70% bleaching, the extent of binding declined gradually to low levels characteristic of unbleached retinas. The period required for half-completion of the decline was approximately 10(3) s. A gradual decline in G binding, from a rapidly developing peak value, was also observed with an increasing period of exposure to intense light. Viewed in the context of previous electrophysiological data, our results indicate that sustained bleaching desensitization of the rods does not depend upon a persisting state of "tight binding" (immobilization) of G-protein by bleached visual pigment.     

Interaction of netropsin and distamycin with deoxyribonucleic acid: electric dichroism study

We report dichroism and equilibrium binding studies of netropsin (Net) and distamycin A3 (Dist) binding to deoxyribonucleic acid (DNA). We show that at low degrees of binding (r) to calf thymus DNA, Net induces a considerable increase in the apparent DNA length (14 A/drug molecule bound), closely analogous to the results reported earlier for Dist. In addition, we show that chicken erythrocyte DNA shows length changes similar to those of calf thymus DNA upon distamycin binding. DNA length reaches a maximum at 1 bound drug/20-30 base pairs and then decreases to its initial value by r = 0.1. This effect is not seen for two other DNAs with nearly identical A + T base pair content and may therefore arise from the details of base sequence or base modification in eukaryotic DNA. We also show that Dist binding to calf thymus DNA at low r values is positively cooperative and shows a DNA affinity which is primarily nonionic. We demonstrate that independent of the DNA to which they are bound, the Net and Dist transition moments are inclined by 43 +/- 3 degrees from the helix axis, consistent with the idea that both drugs bind inside and parallel to the DNA small groove. From dichroism measurements, we show that the conformational change induced in calf thymus DNA by Dist does not kink or bend the helix and does not substantially alter the average inclination of the bases. Finally, we outline a statistical mechanical theory for calculation of binding isotherms when binding is coupled to a DNA structural change.