194 research outputs found
Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish
The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe
Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus
Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory
A comparative study of the effects of genistein and 2-methoxyestradiol on the proteolytic balance and tumour cell proliferation
Numerical relations and skill level constrain co-adaptive behaviors of agents in sports teams
Similar to other complex systems in nature (e.g., a hunting pack, flocks of birds), sports teams have been modeled as social neurobiological systems in which interpersonal coordination tendencies of agents underpin team swarming behaviors. Swarming is seen as the result of agent co-adaptation to ecological constraints of performance environments by collectively perceiving specific possibilities for action (affordances for self and shared affordances). A major principle of invasion team sports assumed to promote effective performance is to outnumber the opposition (creation of numerical overloads) during different performance phases (attack and defense) in spatial regions adjacent to the ball. Such performance principles are assimilated by system agents through manipulation of numerical relations between teams during training in order to create artificially asymmetrical performance contexts to simulate overloaded and underloaded situations. Here we evaluated effects of different numerical relations differentiated by agent skill level, examining emergent inter-individual, intra- and inter-team coordination. Groups of association football players (national - NLP and regional-level - RLP) participated in small-sided and conditioned games in which numerical relations between system agents were manipulated (5v5, 5v4 and 5v3). Typical grouping tendencies in sports teams (major ranges, stretch indices, distances of team centers to goals and distances between the teams' opposing line-forces in specific team sectors) were recorded by plotting positional coordinates of individual agents through continuous GPS tracking. Results showed that creation of numerical asymmetries during training constrained agents' individual dominant regions, the underloaded teams' compactness and each team's relative position on-field, as well as distances between specific team sectors. We also observed how skill level impacted individual and team coordination tendencies. Data revealed emergence of co-adaptive behaviors between interacting neurobiological social system agents in the context of sport performance. Such observations have broader implications for training design involving manipulations of numerical relations between interacting members of social collectives
Double trouble at high density::Cross-level test of ressource-related adaptive plasticity and crowding-related fitness.
Population size is often regulated by negative feedback between population density and individual fitness. At high population densities, animals run into double trouble: they might concurrently suffer from overexploitation of resources and also from negative interference among individuals regardless of resource availability, referred to as crowding. Animals are able to adapt to resource shortages by exhibiting a repertoire of life history and physiological plasticities. In addition to resource-related plasticity, crowding might lead to reduced fitness, with consequences for individual life history. We explored how different mechanisms behind resource-related plasticity and crowding-related fitness act independently or together, using the water flea Daphnia magna as a case study. For testing hypotheses related to mechanisms of plasticity and crowding stress across different biological levels, we used an individual-based population model that is based on dynamic energy budget theory. Each of the hypotheses, represented by a sub-model, is based on specific assumptions on how the uptake and allocation of energy are altered under conditions of resource shortage or crowding. For cross-level testing of different hypotheses, we explored how well the sub-models fit individual level data and also how well they predict population dynamics under different conditions of resource availability. Only operating resource-related and crowding-related hypotheses together enabled accurate model predictions of D. magna population dynamics and size structure. Whereas this study showed that various mechanisms might play a role in the negative feedback between population density and individual life history, it also indicated that different density levels might instigate the onset of the different mechanisms. This study provides an example of how the integration of dynamic energy budget theory and individual-based modelling can facilitate the exploration of mechanisms behind the regulation of population size. Such understanding is important for assessment, management and the conservation of populations and thereby biodiversity in ecosystems
Beyond R0 : demographic models for variability of lifetime reproductive output
© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e20809, doi:10.1371/journal.pone.0020809.The net reproductive rate measures the expected lifetime reproductive output of an individual, and plays an important role in demography, ecology, evolution, and epidemiology. Well-established methods exist to calculate it from age- or stage-classified demographic data. As an expectation, provides no information on variability; empirical measurements of lifetime reproduction universally show high levels of variability, and often positive skewness among individuals. This is often interpreted as evidence of heterogeneity, and thus of an opportunity for natural selection. However, variability provides evidence of heterogeneity only if it exceeds the level of variability to be expected in a cohort of identical individuals all experiencing the same vital rates. Such comparisons require a way to calculate the statistics of lifetime reproduction from demographic data. Here, a new approach is presented, using the theory of Markov chains with rewards, obtaining all the moments of the distribution of lifetime reproduction. The approach applies to age- or stage-classified models, to constant, periodic, or stochastic environments, and to any kind of reproductive schedule. As examples, I analyze data from six empirical studies, of a variety of animal and plant taxa (nematodes, polychaetes, humans, and several species of perennial plants).Supported by National Science Foundation Grant DEB-0816514 and by a Research Award from the Alexander von Humboldt Foundation
Phenotype Enhancement Screen of a Regulatory spx Mutant Unveils a Role for the ytpQ Gene in the Control of Iron Homeostasis
Spx is a global regulator of genes that are induced by disulfide stress in Bacillus subtilis. The regulon that it governs is comprised of over 120 genes based on microarray analysis, although it is not known how many of these are under direct Spx control. Most of the Spx-regulated genes (SRGs) are of unknown function, but many encode products that are conserved in low %GC Gram-positive bacteria. Using a gene-disruption library of B. subtilis genomic mutations, the SRGs were screened for phenotypes related to Spx-controlled activities, such as poor growth in minimal medium and sensitivity to methyglyoxal, but nearly all of the SRG mutations showed little if any phenotype. To uncover SRG function, the mutations were rescreened in an spx mutant background to determine which mutant SRG allele would enhance the spx mutant phenotype. One of the SRGs, ytpQ was the site of a mutation that, when combined with an spx null mutation, elevated the severity of the Spx mutant phenotype, as shown by reduced growth in a minimal medium and by hypersensitivity to methyglyoxal. The ytpQ mutant showed elevated oxidative protein damage when exposed to methylglyoxal, and reduced growth rate in liquid culture. Proteomic and transcriptomic data indicated that the ytpQ mutation caused the derepression of the Fur and PerR regulons of B. subtilis. Our study suggests that the ytpQ gene, encoding a conserved DUF1444 protein, functions directly or indirectly in iron homeostasis. The ytpQ mutant phenotype mimics that of a fur mutation, suggesting a condition of low cellular iron. In vitro transcription analysis indicated that Spx stimulates transcription from the ytpPQR operon within which the ytpQ gene resides. The work uncovers a link between Spx and control of iron homeostasis
Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms
Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration
Human and mouse essentiality screens as a resource for disease gene discovery.
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery
Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes
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