Narrow Results

Cerium oxide (CeO${}_2)$ and yttrium oxide (Y₂O${}_3)$ nanoparticles possess interesting surface properties and interfacial interactions that make them attractive candidates for various applications. This study presents a comprehensive investigation into the synthesis and toxicity assessment of yttrium-doped cerium oxide (Ce-Y) nanocomposite using a combination of analytical techniques and biological assays. The nanocomposite was characterized using UV–Vis spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), electron microscopy imaging, dynamic light scattering (DLS), and zeta potential measurements to elucidate their structural, optical and physicochemical properties. The synthesized nanocomposite exhibited distinctive absorption spectra and precise alignment of diffraction peaks, confirming the successful incorporation of yttrium ions into the cerium oxide lattice. Electron microscopy images revealed well-dispersed yttrium particles within the ceria matrix, indicating uniform distribution and morphology. DLS and zeta potential analysis provided insights into the size distribution and stability of the nanocomposite. Furthermore, in vivo toxicity assessment using Drosophila melanogaster model revealed no significant toxicity of Ce:Y nanocomposite, as evidenced by survival assay and behavioral assays. Superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were also evaluated, demonstrating no discernible nanoparticle-induced toxicity. Overall, this study highlights the potential applications of Ce:Y nanocomposite and underscores the importance of comprehensive toxicity evaluation in nanomaterial development.

RNA-seq is a high-throughput Next-sequencing technique for estimating the concentration of all transcripts in a transcriptome. The method involves complex preparatory and post-processing steps which can introduce bias, and the technique produces a large amount of data [7, 19]. Two important challenges in processing RNA-seq data are therefore the ability to process a vast amount of data, and methods to quantify the bias in public RNA-seq datasets. We describe a novel analysis method, based on analysing sequence motif correlations, that employs MapReduce on Apache Spark to quantify bias in Next-generation sequencing (NGS) data at the deep exon level. Our implementation is designed specifically for processing large datasets and allows for scalability and deployment on cloud service providers offering MapReduce. In investigating the wild and mutant organism types in the species D. melanogaster we have found that motifs with runs of Gs (or their complement) exhibit low motif-pair correlations in comparison with other motif-pairs. This is independent of the mean exon GC content in the wild type data, but there is a mild dependence in the mutant data. Hence, whilst both datasets show the same trends, there is however significant variation between the two samples.

It is well established in Traditional Chinese Medicine that certain natural products, such as male silkworm moths, have different therapeutic effects on men than on women. These natural products have been used as dietary supplements specifically formulated for men or for women. However, this presumed sex-specific effect of certain natural products has not yet been confirmed experimentally with animal models or in human clinical trials. Here, using the fruit fly (Drosophila melanogaster) as a longevity model, we examined the effect of Hu-Bao (HB) and Seng-Bao (SB), two marketed health products made from a mixture of natural ingredients. Our results convincingly demonstrate that the effect of HB and SB are indeed specific for the male fly. The life-span of the male was significantly increased when HB or SB was added to the culture medium. In contrast, neither HB nor SB had much effect on the female fly. Upon removal of the male silkworm moth ingredient from HB or SB, the life-span prolongation effect of HB and SB was drastically diminished. Only with the addition of the male silkworm moth did the culture medium show a statistically significant life-span prolongation effect. This result suggests that the male silkworm moth is a key ingredient, in combination with other components, for specific prolongation of the life-span of male flies.

Drinking colloidal gold as elixir of life is an age-old practice worldwide. A large body of data containing patients' experiences after intake of colloidal gold for long duration would be available in the medical records of hospitals. ZnO has been approved by FDA for topical use and not for oral intake. Drosophila melanogaster (wild type) strains were fed with physiologically relevant concentrations of nano-gold and nano-ZnO along with appropriate controls. Citrate-capped nano-gold (average particle size is 15–20 nm) synthesized by reducing hydrogen tetrachloroaurate with 1% trisodium citrate and custom-made nano-ZnO, purchased from M K Implex, Canada (average particle size 50 nm) were used as treatments. Microarray studies revealed that fly trehalose receptor genes, Tre and Tre1, are both unaffected after nano-gold and nano-ZnO treatment. Gr64 subfamily members (encoding sugar receptors like glucose, sucrose, and maltose), for example, Gr64a-b become downregulated, but Gr64c, Gr64d, Gr64f remain unaltered in case of both the treatments. Among bitter receptor genes, Gr66a is the most well studied and shows significant downregulation by nano-gold and not by nano-ZnO. Ppk11 and Ppk19 are gustatory ion channel genes which modulate salt perception. Ppk11 was found to be downregulated by both nano-gold and nano-ZnO, while ppk19 expression is suppressed by nano-gold treatment but not by nano-ZnO. The effects of these two nanoparticles on pheromone receptors (Gr32a, Gr39a, and Gr68a) and _CO2 receptors (Gr21a and Gr63a) are presented. To the best of our knowledge, this is the first report on the effect of pure nanoparticles on gustation. Data has been analyzed in the light of the age-old tradition of oral administration of the nano-gold viz-a-viz topical use of nano-ZnO. These results would have far reaching implications in the design of nano-gold mediated oral drug delivery of cancer and other drugs as well as nano-ZnO coated drugs/cosmetics and nano-ZnO carrier based drug delivery in skins and in other topical applications.

Macrochaetes (large bristles) are sensor organs of the Drosophila peripheral nervous system with a function of mechanoreceptors. An adult mechanoreceptor comprises four specialized cells: shaft (trichogen), socket (tormogen), neuron, and glial cell (thecogen). All these cells originate from a single cell, the so-called sensor organ precursor (SOP) cell. Separation of the SOP cell from the encompassing cells of the imaginal disc initiates a multistage process of sensory organ development. A characteristic feature of the SOP cell is the highest amount of the proneural proteins AS-C as compared with the encompassing ectodermal cells. The accumulation of proneural proteins and maintenance of their amount in the SOP cell at a necessary level is provided by the gene network with the achaete–scute gene complex (AS-C) as its key component. The activity of this complex is controlled by the central regulatory circuit (CRC). The CRC comprises the genes hairy, senseless (sens), charlatan (chn), scratch (scrt), daughterless (da), extramacrochaete (emc), and groucho (gro), coding for the transcription factors involved in the system of direct links and feedbacks and implementation of activation–repression relationships between the CRC components. The gene phyllopod (phyl), involved in degradation of the AS-C proteins, is also associated with the CRC functioning. In this paper, we propose a mathematical model for the CRC functioning as a regulator of the amount of proneural AS-C proteins in the SOP cell taking into account their degradation. The modeling has demonstrated that a change in the amount of proneural proteins in the SOP cell is stepwise rather than strictly monotonic. This prediction can be tested experimentally.

Commonly among the model parameters characterizing complex biological systems are those that do not significantly influence the quality of the fit to experimental data, so-called “sloppy” parameters. The sloppiness can be mathematically expressed through saturating response functions (Hill’s, sigmoid) thereby embodying biological mechanisms responsible for the system robustness to external perturbations. However, if a sloppy model is used for the prediction of the system behavior at the altered input (e.g. knock out mutations, natural expression variability), it may demonstrate the poor predictive power due to the ambiguity in the parameter estimates. We introduce a method of the predictive power evaluation under the parameter estimation uncertainty, Relative Sensitivity Analysis. The prediction problem is addressed in the context of gene circuit models describing the dynamics of segmentation gene expression in Drosophila embryo. Gene regulation in these models is introduced by a saturating sigmoid function of the concentrations of the regulatory gene products. We show how our approach can be applied to characterize the essential difference between the sensitivity properties of robust and non-robust solutions and select among the existing solutions those providing the correct system behavior at any reasonable input. In general, the method allows to uncover the sources of incorrect predictions and proposes the way to overcome the estimation uncertainties.

We review some recent results of modeling the pattern formation by segmentation genes during the early development of the Drosophila embryo. The study of gene expression patterns is based on the “gene circuit” method consisting of four steps: obtaining gene expression experimental data, formulating a model, fitting the model to the data, and inferring new biology from the analysis of results. The biological data has the form of processed images of immunostained embryos and is adopted in the form of concentration curves for proteins coded by various segmentation genes averaged over many embryos. The model is formulated as deterministic reaction-diffusion equations with protein concentrations in many cell nuclei as state variables. The values of parameters in the model are calculated by fitting the solution of model equations to the experimental concentration curves. We also describe how the gene circuit approach allows one to elucidate a role in the pattern formation played by nuclear cleavages in the developing embryo.

Exploiting the ortholog/homolog information now available from the complete genomic sequences of twelve species of Drosophila, we have investigated the ability of regulatory site recognition methods to find regulatory changes for orthologs linked to chromosomal rearrangements. This has made use of the wealth of synteny information among these species. By comparing orthologs in multiple species, we found that the breakpoint of chromosomal rearrangements could have had an impact on regulatory changes of genes next to it with respect to the gene function and location. Extensions of our approach could be used to shed light on the role of gene regulation in the evolutionary adaptation to different environmental conditions.

Trade-offs among life-history traits are often thought to constrain the evolution of populations. Here we report the disappearance of a trade-off between early fecundity on the one hand, and late-life fecundity, starvation resistance, and longevity on the other, over 10 yr of laboratory selection for late-life reproduction. Whereas the selected populations showed an initial depression in early-life fecundity, they later converged upon the controls and then surpassed them. The evolutionary loss of the trade-off among life-history traits is considered attributable to the following factors: (1) the existence of differences in the culture regimes of the short- and long-generation populations other than the demographic differences deliberately imposed; (2) adaptation of one or both of these sets of populations to the unique aspects of their culture regimes; (3) the existence of an among-environment trade-off in the expression of early fecundity in the two culture regimes, as reflected in assays that mimic those regimes. The trade-off between early and late-life reproductive success, as manifest among divergently selected populations, is apparent or not depending on the assay environment. This demonstration that strong genotype-by-environment interactions can obscure a fundamental trade-off points to the importance of controlling all aspects of the culture regime of experimental populations and the difficulty of doing so even in the laboratory.

Tests for the causal involvement of specific physiological mechanisms in the control of aging require evidence that these mechanisms can be used to increase longevity or reproductive lifespan. Selection for later reproduction in Drosophila has been shown to lead to increased longevity, as well as increased resistance to starvation and desiccation stresses. Selection for increased resistance to starvation and desiccation in Drosophila melanogaster is here shown to lead to increased longevity, indicating that alleles that increase stress resistance also may increase longevity. The responses of desiccation and starvation resistance to selection are partly independent of each other, indicating a multiplicity of physiological mechanisms involved in selectively postponed aging, and thus aging in general.

Studies with the fruit fly, Drosophila melanogaster, have repeatedly shown that selection for postponed reproduction leads to increases in mean life span and increased stress resistance; including increased resistance to desiccation, starvation and ethanol vapors. We show that desiccation resistance declines with age in both short- and long-lived flies suggesting that desiccation resistance may serve as a useful biomarker for aging-related declines in physiological performance. We examined the physical basis of desiccation resistance in five replicate populations selected for postponed reproduction and five replicate control populations. The variables examined were water content, rates of water loss during desiccation, and water content at time of death due to desiccation. In the absence of desiccation stress, both the flies exhibiting postponed senescence and their controls maintained constant water content throughout their lifetimes. In the presence of desiccation stress, the short-lived flies showed significantly higher rates of water loss at all ages than did the long-lived flies. Flies from the two treatments did not differ in water content at death. Our results indicate that water loss rates are the major determinant of desiccation resistance. Water loss rates are under genetic control and covary with age in populations with genetically-determined postponed senescence. © 2000 Published by Elsevier Science Inc.

Earlier experiments have shown that the evolution of postponed senescent populations can be achieved by selection on either demographic or stress resistance characters. Both types of selection have produced results in which survival characters (stress resistance and longevity) have apparently traded-off against early-life fecundity.

Here we present the results of a series of experiments in which an environmental variable – the level of live yeast inoculate applied to the substrate – produces a qualitatively similar phenotypic response: longevity and starvation resistance are enhanced by lower yeast levels, at the expense of fecundity. For the starvation resistance versus fecundity experiments we show a negative and linear relationship between the norms of reaction for each character across a gradient of yeast levels. This phenotypic trade-off is stable across the 20 populations and 4 selection treatments reported on here, and its general agreement with earlier selection results suggests that the evolutionary response and the phenotypically plastic response may share a common physiological basis. However, an important discrepancy in the lifetime fecundity data between the selection response and the dietary manipulations preclude strict analogy. The results broadly conform to a simple “Y-model” of allocation, in which a limited resource is divided between survival and reproduction; here the characters are starvation resistance and longevity versus fecundity.

One of the major issues in research on life-history evolution is the relationship between trade-offs inferred from responses to selection and trade-offs inferred from responses to phenotypic manipulation (Partridge and Harvey, 1988). Reznick (1985, 1992), among others (e.g. Rose et al., 1987), has argued that hypotheses about the role of trade-offs in evolution depend critically on the effects of alleles, which may be different from the physiological interactions that might give rise to a phenotypic trade-off. One factor that has limited the pertinence of this debate is the relative lack of experimental systems in which both genetic and non-genetic trade-offs have been delineated.

Laboratory evolution of life-history in Drosophila melanogaster has been extensively exploited in the study of evolutionary genetic trade-offs (e.g. Rose and Charlesworth, 1980; Rose, 1984; Luckinbill et al., 1984; Service and Rose, 1985; Luckinbill and Clare, 1985; Service et al., 1988; Hutchinson et al., 1991). In addition, there have been a number of Drosophila experiments that indicate considerable phenotypic plasticity for life-history characters under environmental manipulation (Partridge and Farquhar, 1981; Partridge, 1987; Partridge et al., 1986, 1987; Luckinbill et al., 1988; Service, 1989). An obvious strategy, given these results, is to attempt to identify common patterns in these two types of experiment, and then seek mechanisms uniting the genetic and manipulative findings.

A central theme of many theories concerning evolutionary and other tradeoffs is that of energetic allocation (e.g. Gadgil and Bossert, 1970). In the context of life-history evolution, the phenomenon of energetic allocation has surfaced in research indicating the role of allocation of energetic reserves, specifically lipid and glycogen, between survival and reproductive functions in the evolution of postponed aging in D. melanogaster (Service, 1987, 1989; Graves et al., 1992). But possibly analogous phenomena arise in the dietary restriction literature of gerontology, in which reduction in the caloric intake of rodents appears to give rise to increased longevity as a result of a shift of resources from reproductive activity to adult survival (Holehan and Merry, 1985; Masoro, 1988; Rose, 1991). This parallelism suggests the possibiliy that genetically-mediated allocation of energetic reserves in D. melanogaster could proceed by similar mechanisms to those of nutritionally-mediated allocation, as in rodent dietary restriction. A problem facing this hypothesis is that dietary restriction in Drosophila has given inconsistent results, with some failures to discover any apparent enhancement of longevity with dietary restriction (e.g. Le Bourg and Medioni, 1991). Therefore, exploration of this possible line of research connecting plasticity and evolutionary response via energetic metabolism requires elucidation of the nature of dietary restriction responses in D. melanogaster.

In this article, we report dietary manipulation experiments with D. melanogaster that appear to mimic both evolutionary trade-offs between survival and reproduction as well as the phenotypic trade-offs observed in rodent caloric restriction, at least with respect to some characters. In addition, we present evidence that energetic metabolism determines at least part of the phenotypic trade-off between survival and reproduction in these populations.

The effects of superoxide dismutase on aging were tested using two differt experimental approaches. In the first, replicated populations with postponed aging were compared with their controls for frequencies of electrophoretic alleles at the SOD locus. Populations with postponed aging had consistently greater frequencies of the allele coding for more active SOD protein. This allele was not part of a segregating inversion polymorphism. The second experimental approach was the extraction of SOD alleles from different natural populations followed by the construction of different SOD genotypes on hybrid genetic backgrounds. This procedure did not uncover any statistical effect of SOD genotype on longevity or fecundity. There were large effects on longevity and fecundity due to the family from which a particular SOD genotype was derived. To detect the effects of SOD genotypes on longevity with high probability would require a ten-fold increase in the number of families used.

Five populations of Drosophila melanogaster that had been selected for postponed aging were compared with five control populations using two-dimensional protein gel electrophoresis. The goals of the study were to identify specific proteins associated with postponed aging and to survey the population genetics of the response to selection. A total of 321 proteins were resolvable per population; these proteins were scored according to their intensity. The resulting data were analyzed using resampling, combinatoric, and maximum parsimony methods. The analysis indicated that the populations with postponed aging were different from their controls with respect to specific proteins and with respect to the variation between populations. The populations selected for postponed aging were more heterogeneous between populations than were the control populations. Maximum parsimony trees separate the selected populations, as a group, from their controls, thereby exhibiting a homoplastic pattern.

Drosophila melanogaster populations that exhibit constrasting life histories as a result of laboratory selection were compared at several potentially relevant enzyme loci. Selection regimes included postponed reproduction, accelerated development, and intermediate generation time. Each selection regime was represented by fivefold replicated populations maintained for between 50 and 500 generations. For each population, allele frequencies were calculated from frequencies of electrophoretically distinguishable allozymes of alcohol dehydrogenase, α-glycerol-3-phosphate dehydrogenase, phosphoglucomutase, and CuZn-superoxide dismutase. Based on allozyme frequency changes consistent across replicate populations, two of the studied loci responded to both selection for postponed reproduction and selection for accelerated development. The responses to contrasting selection regimes were in opposing directions, suggesting antagonistic pleiotropy.

We selected five-fold replicated lines of Drosophila pseudoobscura, Drosophila hydei, and Drosophila arizonae for postponed aging. After 10 generations of postponed reproduction, female mean longevity had increased in all D. pseudoobscura lines and all D. hydei lines, and male longevity had increased in all D. pseudoobscura lines and all D. arizonae lines. We assayed eight metabolic enzymes for differentiation in allozyme frequencies between control (B) lines and selected (O) lines. Frequencies of phosphoglucomutase allozymes differentiated in response to selection in both species in which this locus was electrophoretically polymorphic. This evolution at the Pgm locus may explain the increased glycogen content associated with postponed aging in Drosophila.

The role of development in the evolution of postponed senescence is poorly understood despite the existence of a major gerontological theory connecting developmental rate to aging. We investigate the role of developmental rate in the laboratory evolution of aging using 24 distinct populations of Drosophila melanogaster. We have found a significant difference between the larval developmental rates of our Drosophila stocks selected for early (B) and late-life (O) fertility. This larval developmental time difference of approximately 12% (O > B) has been stable for at least 5 yr, occurs under a wide variety of rearing conditions, responds to reverse selection, and is shown for two other O-like selection treatments. Emerging adults from lines with different larval developmental rates show no significant differences in weight at emergence, thorax length, or starvation resistance. Long-developing lines (O, CO, and CB) have greater survivorship from egg to pupa and from pupa to adult, with and without strong larval competition. Crosses between slower developing populations, and a variety of other lines of evidence, indicate that neither mutation accumulation nor inbreeding depression are responsible for the extended development of our late-reproduced selection treatments. These results stand in striking contrast to other recent studies. We argue that inbreeding depression and inadvertent direct selection in other laboratories' culture regimes explain their results. We demonstrate antagonistic pleiotropy between developmental rate and preadult viability. The absence of any correlation between longevity and developmental time in our stocks refutes the developmental theory of aging.

Developmental time is a trait of great relevance to fitness in all organisms. In holometabolous species that occupy ephemeral habitat, like Drosophila melanogaster, the impact of developmental time upon fitness is further exaggerated. We explored the trade-offs surrounding developmental time by selecting 10 independent populations from two distantly related selection treatments (CB_1-5 and CO_1-5) for faster development. After 125 generations, the resulting accelerated populations (ACB_1-5 and ACO_1-5) displayed net selection responses for development time of -33.4 hours (or 15%) for ACB and -38.6 hours (or 17%) for ACO. Since most of the change in egg-to-adult developmental time was accounted for by changes in larval duration, the “accelerated” larvae were estimated to develop 25-30% faster than their control/ancestor populations. The responses of ACB and ACO lines were remarkably parallel, despite being founded from populations evolved independently for more than 300 generations. On average, these “A” populations developed from egg to adult in less than eight days and produced fertile eggs less than 24 hours after emerging. Accelerated populations showed no change in larval feeding rate, but a reduction in pupation height, the latter being a trait relating to larval energetic expenditure in wandering prior to pupation. This experiment demonstrates the existence of a negative evolutionary correlation between preadult developmental time and viability, as accelerated populations experienced a severe cost in preadult survivorship. In the final assay generation, viability of accelerated treatments had declined by more than 10%, on average. A diallel cross demonstrated that the loss of viability in the ACO lines was not due to inbreeding depression. These results suggest the existence of a rapid development syndrome, in which the fitness benefits of fast development are balanced by fitness costs resulting from reduced preadult survivorship, marginal larval storage of metabolites, and reduced adult size.