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BMC Proceedings Nov 2011Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions...
Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions that show evidence of functionality. In this study we use the 1000 Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to compare rare variant densities across seven populations. We made the comparisons using regressions of rare variants on total variant counts per gene for each population and Tajima's D values calculated for each gene in each population, using data on 3,205 genes. We found that the populations clustered by continent for both the regression slopes and Tajima's D values, with the African populations (Yoruba and Luhya) showing the highest density of rare variants, followed by the Asian populations (Han and Denver Chinese followed by the Japanese) and the European populations (CEPH [European-descent] and Tuscan) with the lowest densities. These significant differences in rare variant densities across populations seem to translate to measures of the rare variant density more commonly used in rare variant association analyses, suggesting the need to adjust for ancestry in such analyses. The selection signal was high for AHNAK, HLA-A, RANBP2, and RGPD4, among others. RANBP2 and RGPD4 showed a marked difference in rare variant density and potential selection between the Luhya and the other populations. This may suggest that differences between populations should be considered when delimiting genomic regions according to functionality and that these differences can create potential for disease heterogeneity.
PubMed: 22373165
DOI: 10.1186/1753-6561-5-S9-S39 -
Nature Communications May 2020Facilitation studies typically compare plants under differential stress levels with and without neighbors, while the density of neighbors has rarely been addressed....
Facilitation studies typically compare plants under differential stress levels with and without neighbors, while the density of neighbors has rarely been addressed. However, recent empirical studies indicate that facilitation may be density-dependent too and peak at intermediate neighbor densities. Here, we propose a conceptual model to incorporate density-dependence into theory about changes of plant-plant interactions under stress. To test our predictions, we combine an individual-based model incorporating both facilitative response and effect, with an experiment using salt stress and Arabidopsis thaliana. Theoretical and experimental results are strikingly consistent: (1) the intensity of facilitation peaks at intermediate density, and this peak shifts to higher densities with increasing stress; (2) this shift further modifies the balance between facilitation and competition such that the stress-gradient hypothesis applies only at high densities. Our model suggests that density-dependence must be considered for predicting plant-plant interactions under environmental change.
Topics: Acclimatization; Arabidopsis; Ecosystem; Models, Biological; Plant Development; Plant Physiological Phenomena; Population Dynamics; Stress, Physiological
PubMed: 32439842
DOI: 10.1038/s41467-020-16286-6 -
Frontiers in Behavioral Neuroscience 2023Despite its popularity in research, there is very little scientifically validated knowledge about the best practices on zebrafish () husbandry, which has led to several...
INTRODUCTION
Despite its popularity in research, there is very little scientifically validated knowledge about the best practices on zebrafish () husbandry, which has led to several facilities having their own husbandry protocols. This study was performed to expand knowledge on the effects of enrichment and fish density on the welfare of zebrafish, with hopes of providing a scientific basis for future recommendations and legislations.
METHODS
Zebrafish were reared at three different stocking densities, (1, 3 or 6 fish/L), in tanks with or without environmental enrichment. Agonistic behavior was observed twice a week for 9 weeks directly in the housing tanks. Aspects of welfare is known to be reflected in neuroendocrine stress responses. Thus, cortisol secretion in response to lowering the water level was analyzed for each group. In addition, we assessed cortisol secretion in response to confinement and risk-taking behavior (boldness) using the novel tank diving test for individual fish. At termination of the experiment fish were subjected to stress by transfer to a novel environment and brain tissue was sampled for analysis of brain monoaminergic activity.
RESULTS
Fish kept at the lowest density (1 fish/L) showed a significantly higher level of aggression than fish kept at 3 or 6 fish/L. Moreover, fish kept at this low density showed significantly higher cortisol secretion on a group level than fish kept at the higher stocking densities, when subjected to lowering of the water level. Keeping fish at 1 fish/L also had effects on brain monoamines, these fish showing higher brain dopamine concentrations but lower dopamine turnover than fish kept at higher densities. Neither stocking density or enrichment had any clear effects on the behavior of individual fish in the novel tank diving test. However, fish kept at high densities showed lower and more variable growth rates than fish kept at 1 fish/L.
DISCUSSION
Taken together these results suggest that zebrafish should not be kept at a density of 1 fish/L. The optimal stocking density is likely to be in the range of 3-6 fish/L.
PubMed: 37456810
DOI: 10.3389/fnbeh.2023.1204021 -
PloS One 2017Mast cells and basophils depend on aggregation of the high-affinity IgE receptor, FceRI, to initiate secretion. A variety of studies have shown that FceRI densities vary...
Mast cells and basophils depend on aggregation of the high-affinity IgE receptor, FceRI, to initiate secretion. A variety of studies have shown that FceRI densities vary 100 fold among subjects' basophils and it has been speculated that high densities might be responsible for unusual behaviors of the cells, notably sensitivity to certain monomeric IgE antibodies or spontaneous release. These studies experimentally examined the density dependence of spontaneous release and signaling element expression in subjects' basophils with FceRI densities ranging from approximately 6000 to 600,000 per cell. Through the use of numerical simulation, this study examined the expectations for spontaneous receptor aggregation and aggregate persistence at densities of FceRI ranging from 5000 to 500,000. Experimentally, FceRI density was not associated with greater spontaneous histamine release even when secretion was enhanced by the inclusion of deuterium oxide in the buffers. There was also no association of 15 activating or de-activating signaling elements with FceRI density. The numerical simulations demonstrated that at densities of ≈500,000 receptors, 13% of receptors were involved in transient aggregates at any given moment but that these aggregates rarely persisted for greater than 10 milliseconds. In contrast, a weak linear antigen aggregator, with ligand affinities known to induce secretion, would generate aggregates persisting for an average of ≈60 milliseconds. These results suggest that although a high density of FceRI likely produces a large number of transient aggregates, these aggregates do not persist long enough to induce signaling that results in secretion and do not induce the cells to alter their expression of several signaling elements known to be important in regulating secretion from human basophils. The results set some boundaries on the aggregation requirements for inducing histamine release from human basophils.
Topics: Basophils; Humans; Immunoglobulin E; Nuclear Proteins
PubMed: 28671980
DOI: 10.1371/journal.pone.0179734 -
Frontiers in Integrative Neuroscience 2022Neuronal densities vary enormously across sites within a brain. Does the density of the capillary bed vary accompanying the presumably larger energy requirement of sites...
Neuronal densities vary enormously across sites within a brain. Does the density of the capillary bed vary accompanying the presumably larger energy requirement of sites with more neurons, or with larger neurons, or is energy supply constrained by a mostly homogeneous capillary bed? Here we find evidence for the latter, with a capillary bed that represents typically between 0.7 and 1.5% of the volume of the parenchyma across various sites in the mouse brain, whereas neuronal densities vary by at least 100-fold. As a result, the ratio of capillary cells per neuron decreases uniformly with increasing neuronal density and therefore with smaller average neuronal size across sites. Thus, given the relatively constant capillary density compared to neuronal density in the brain, blood and energy availability per neuron is presumably dependent on how many neurons compete for the limited supply provided by a mostly homogeneous capillary bed. Additionally, we find that local capillary density is not correlated with local synapse densities, although there is a small but significant correlation between lower neuronal density (and therefore larger neuronal size) and more synapses per neuron within the restricted range of 6,500-9,500 across cortical sites. Further, local variations in the glial/neuron ratio are not correlated with local variations in the number of synapses per neuron or local synaptic densities. These findings suggest that it is not that larger neurons, neurons with more synapses, or even sites with more synapses more energy, but simply that larger neurons (in low density sites) have more energy available per cell and for the totality of its synapses than smaller neurons (in high density sites) due to competition for limited resources supplied by a capillary bed of fairly homogeneous density throughout the brain.
PubMed: 36105258
DOI: 10.3389/fnint.2022.760887 -
Korean Journal of Ophthalmology : KJO Oct 2021To evaluate the effect of smoking on retinal thickness and macular and peripapillary vascular density in thyroid eye disease (TED).
PURPOSE
To evaluate the effect of smoking on retinal thickness and macular and peripapillary vascular density in thyroid eye disease (TED).
METHODS
In this cross-sectional study, subjects diagnosed with TED were analyzed in three groups: smokers, passive smokers, and non-smokers. Ganglion cell complex thickness, total retinal thickness, macular superficial vascular plexus densities, deep vascular plexus densities, optic nerve head, and radial peripapillary capillary density were measured in each group.
RESULTS
Twenty-two eyes (21.6%) of active smokers, 11 eyes (10.8%) of passive smokers, and 69 eyes (67.6%) of non-smokers constitute the study subjects. Twenty-one eyes (12.6%) had active status (clinical activity score ≥3), 77 eyes (46.1%) were neither active nor compressive, four eyes (2.4%) of two patients constituted the compressive group. Age and disease activity adjusted analysis was performed. Ganglion cell complex thickness of smokers was significantly higher than non-smokers in the inferior hemi-parafoveal sector (p = 0.04). Active smokers had significantly higher (p < 0.01) retinal thickness in all sectors compared to non-smokers, except the foveal sector. Smokers had lower superficial vessel density in the superior parafoveal sector compared to non-smokers (p = 0.04). Considering deep vessel densities between smokers and non-smokers, no significant difference was observed. Radial peripapillary capillary densities (significant difference was observed in the whole image and infranasal peripapillary sector), Macular vascular densities (significant difference was observed in parafoveal sectors), and optic nerve head (not reaching statistical significance level in any sectors) were highest in passive smokers.
CONCLUSIONS
Smoking is associated with increased total retinal thickness. Macular vascular densities were not different between smokers and non-smokers in TED.
Topics: Cross-Sectional Studies; Graves Ophthalmopathy; Humans; Microvascular Density; Optic Disk; Retinal Vessels; Smoking; Tomography, Optical Coherence
PubMed: 34344134
DOI: 10.3341/kjo.2021.0059 -
Scientific Reports Nov 2018Increasing planting density is the main method and key management to enhance the grain yield. Preventing lodging and premature senescence in high planting density, and...
Increasing planting density is the main method and key management to enhance the grain yield. Preventing lodging and premature senescence in high planting density, and screening and enhancing the density-tolerance of maize variety is the main goal of agronomy. Differential response of maize hybrids to high plant density greatly affect the dry matter accumulation and its allocation to maize kernel, depending upon various traits responsible for crowding stress tolerance, of which ear characteristics are pivotal. Density resistance as a quality appraisal of certain variety permits the construction of a simple and accurate method to determine this value, useful for plant breeding. Therefore, we created a new quantitative method, which tested several maize varieties planted populary in China (e.g. Zhengdan 958, Xianyu 335, and Denghai 661) to quantify their response to crowding stress through model. We established 13 planting densities (ranging 1.67-16.67 plants m) by adopting fixed line spacing (80 × 40 cm) and then gradually increasing row spacing from 1 m to increasing planting density. A conventional standard plot was also established for verification and evaluation of the plant morphologic characteristics, ear traits, and the yield of maize at various standard densities during 5-year study period. By studying the density-yield relationship, a quantitative model was constructed to identify the density resistance of maize. Grain yield of maize varieties under varying planting densities were simulated, and models of population yield and yield per plant that fitted the data well with high biological significance were produced. From the models, the optimal density of the popular main maize varieties planted in China and the morphological characteristics of each variety at that density were identified. The density-resistance of each variety was referred to as the ear-sensitivity classification. With the highest yield at the optimal density, the plant height of each variety reached 98% to that of tallest plant. The ear/plant ratio was about 0.45, and the ratio between the stem diameter and the largest stem diameter was 0.65-0.80. During the harvest period, the ratio between average single-plant yield and the highest single-plant yield was 0.40-0.50. By gradually increasing planting density, the density resistance of the maize and the changes in yield with density were quantified. Present study provides a convenient tool for the effective selection of varieties by plant breeders through this method and model will help to rapidly identify the density resistance for a new variety and accurate confirmation to optimal planting density, it could be optimized to enable practical production at reasonable planting densities.
Topics: Agriculture; Biomass; Computer Simulation; Models, Statistical; Zea mays
PubMed: 30470761
DOI: 10.1038/s41598-018-35275-w -
Frontiers in Integrative Neuroscience 2022We report in a companion paper that in the mouse brain, in contrast to the 1,000-fold variation in local neuronal densities across sites, capillary density (measured...
We report in a companion paper that in the mouse brain, in contrast to the 1,000-fold variation in local neuronal densities across sites, capillary density (measured both as capillary volume fraction and as density of endothelial cells) show very little variation, of the order of only fourfold. Here we confirm that finding in the rat brain and, using published rates of local blood flow and glucose use at rest, proceed to show that what small variation exists in capillary density across sites in the rat brain is strongly and linearly correlated to variations in local rates of brain metabolism at rest. Crucially, we show that such variations in local capillary density and brain metabolism are not correlated with local variations in neuronal density, which contradicts expectations that use-dependent self-organization would cause brain sites with more neurons to have higher capillary densities due to higher energetic demands. In fact, we show that the ratio of endothelial cells per neuron serves as a linear indicator of average blood flow and glucose use per neuron at rest, and both increase as neuronal density decreases across sites. In other words, because of the relatively tiny variation in capillary densities compared to the large variation in neuronal densities, the anatomical infrastructure of the brain is such that those sites with fewer neurons have more energy supplied per neuron, which matches a higher average rate of energy use per neuron, compared to sites with more neurons. Taken together, our data support the interpretation that resting brain metabolism is not demand-based, but rather limited by its capillary supply, and raise multiple implications for the differential vulnerability of diverse brain areas to disease and aging.
PubMed: 35757100
DOI: 10.3389/fnint.2022.821850 -
PloS One 2021The interaction between a consumer (such as, a predator or a parasitoid) and a resource (such as, a prey or a host) forms an integral motif in ecological food webs, and...
The interaction between a consumer (such as, a predator or a parasitoid) and a resource (such as, a prey or a host) forms an integral motif in ecological food webs, and has been modeled since the early 20th century starting from the seminal work of Lotka and Volterra. While the Lotka-Volterra predator-prey model predicts a neutrally stable equilibrium with oscillating population densities, a density-dependent predator attack rate is known to stabilize the equilibrium. Here, we consider a stochastic formulation of the Lotka-Volterra model where the prey's reproduction rate is a random process, and the predator's attack rate depends on both the prey and predator population densities. Analysis shows that increasing the sensitivity of the attack rate to the prey density attenuates the magnitude of stochastic fluctuations in the population densities. In contrast, these fluctuations vary non-monotonically with the sensitivity of the attack rate to the predator density with an optimal level of sensitivity minimizing the magnitude of fluctuations. Interestingly, our systematic study of the predator-prey correlations reveals distinct signatures depending on the form of the density-dependent attack rate. In summary, stochastic dynamics of nonlinear Lotka-Volterra models can be harnessed to infer density-dependent mechanisms regulating predator-prey interactions. Moreover, these mechanisms can have contrasting consequences on population density fluctuations, with predator-dependent attack rates amplifying stochasticity, while prey-dependent attack rates countering to buffer fluctuations.
Topics: Models, Theoretical; Nonlinear Dynamics; Stochastic Processes
PubMed: 34383811
DOI: 10.1371/journal.pone.0255880 -
MBio Dec 2021Endosymbionts can influence host reproduction and fitness to favor their maternal transmission. For example, endosymbiotic bacteria often cause cytoplasmic...
Endosymbionts can influence host reproduction and fitness to favor their maternal transmission. For example, endosymbiotic bacteria often cause cytoplasmic incompatibility (CI) that kills uninfected embryos fertilized by -modified sperm. Infected females can rescue CI, providing them a relative fitness advantage. -induced CI strength varies widely and tends to decrease as host males age. Since strong CI drives to high equilibrium frequencies, understanding how fast and why CI strength declines with male age is crucial to explaining age-dependent CI's influence on prevalence. Here, we investigate if densities and/or CI gene () expression covary with CI-strength variation and explore covariates of age-dependent -density variation in two classic CI systems. Ri CI strength decreases slowly with Drosophila simulans male age (6%/day), but Mel CI strength decreases very rapidly (19%/day), yielding statistically insignificant CI after only 3 days of Drosophila melanogaster adult emergence. densities and expression in testes decrease as Ri-infected males age, but both surprisingly increase as Mel-infected males age, and CI strength declines. We then tested if phage lysis, Octomom copy number (which impacts Mel density), or host immune expression covary with age-dependent Mel densities. Only host immune expression correlated with density. Together, our results identify how fast CI strength declines with male age in two model systems and reveal unique relationships between male age, densities, expression, and host immunity. We discuss new hypotheses about the basis of age-dependent CI strength and its contributions to prevalence. bacteria are the most common animal-associated endosymbionts due in large part to their manipulation of host reproduction. Many cause cytoplasmic incompatibility (CI) that kills uninfected host eggs. Infected eggs are protected from CI, favoring spread in natural systems and in transinfected mosquito populations where vector-control groups use strong CI to maintain pathogen-blocking at high frequencies for biocontrol of arboviruses. CI strength varies considerably in nature and declines as males age for unknown reasons. Here, we determine that CI strength weakens at different rates with age in two model symbioses. density and CI gene expression covary with Ri-induced CI strength in Drosophila simulans, but neither explain rapidly declining Mel-induced CI in aging D. melanogaster males. Patterns of host immune gene expression suggest a candidate mechanism behind age-dependent Mel densities. These findings inform how age-dependent CI may contribute to prevalence in natural systems and potentially in transinfected systems.
Topics: Animals; Cytoplasm; Drosophila; Drosophila melanogaster; Female; Male; Species Specificity; Symbiosis; Wolbachia
PubMed: 34903056
DOI: 10.1128/mBio.02998-21