Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival

MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over-or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics

Numerical approximation of the generalized regularized long wave equation using Petrov–Galerkin finite element method

The generalized regularized long wave (GRLW) equation has been developed to model a variety of physical phenomena such as ion-acoustic and magnetohydro dynamic waves in plasma,nonlinear transverse waves in shallow water and phonon packets in nonlinear crystals. This paper aims to develop andanalyze a powerful numerical scheme for the nonlinear GRLWequation by Petrov–Galerkin method in which the elementshape functions are cubic and weight functions are quadratic B-splines. The proposed method is implemented to three ref-erence problems involving propagation of the single solitarywave, interaction of two solitary waves and evolution of solitons with the Maxwellian initial condition. The variational for-mulation and semi-discrete Galerkin scheme of the equation are firstly constituted. We estimate rate of convergence of such an approximation. Using Fourier stability analysis of thelinearized scheme we show that the scheme is uncondition-ally stable. To verify practicality and robustness of the new scheme error norms L2, L∞ and three invariants I1, I2,and I3 are calculated. The computed numerical results are compared with other published results and confirmed to be precise and effective

Basis Functions for Linear-Scaling First-Principles Calculations

In the framework of a recently reported linear-scaling method for density-functional-pseudopotential calculations, we investigate the use of localized basis functions for such work. We propose a basis set in which each local orbital is represented in terms of an array of `blip functions'' on the points of a grid. We analyze the relation between blip-function basis sets and the plane-wave basis used in standard pseudopotential methods, derive criteria for the approximate equivalence of the two, and describe practical tests of these criteria. Techniques are presented for using blip-function basis sets in linear-scaling calculations, and numerical tests of these techniques are reported for Si crystal using both local and non-local pseudopotentials. We find rapid convergence of the total energy to the values given by standard plane-wave calculations as the radius of the linear-scaling localized orbitals is increased.Comment: revtex file, with two encapsulated postscript figures, uses epsf.sty, submitted to Phys. Rev.

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Parity conserving gamma asymmetry in n-p radiative capture

The importance of n-p radiative capture, utilizing polarized cold neutrons, as a means of measuring the weak pion coupling constant is reviewed. Parity conserving processes of the form k_gamma*[s_n,k_n] can contribute to the s_n*k_gamma photon asymmetry in any such experiment, if the apparatus is not perfectly symmetric. For an incident laboratory neutron energy of 0.003 eV a value of A^{PC}_{gamma}=0.67*10^{-8} is obtained for two different potential models (Argonne AV14 and Nijmegen Reid93). Serving as an extreme test case, the Reid soft core potential yields 0.61*10^{-8}, close to the result of the contemporary forces. Implications for extracting the weak pion coupling constant and for monitoring the beam polarization are discussed.Comment: 8 page

Field evidence challenges the often-presumed relationship between early male maturation and female-biased sexual size dimorphism

Female-biased sexual size dimorphism (SSD) is often considered an epiphenomenon of selection for the increased mating opportunities provided by early male maturation (i.e., protandry). Empirical evidence of the adaptive significance of protandry remains nonetheless fairly scarce. We use field data collected throughout the reproductive season of an SSD crab spider, Mecaphesa celer, to test two hypotheses: Protandry provides fitness benefits to males, leading to female-biased SSD, or protandry is an indirect consequence of selection for small male size/large female size. Using field-collected data, we modeled the probability of mating success for females and males according to their timing of maturation. We found that males matured earlier than females and the proportion of virgin females decreased abruptly early in the season, but unexpectedly increased afterward. Timing of female maturation was not related to clutch size, but large females tended to have more offspring than small females. Timing of female and male maturation was inversely related to size at adulthood, as early-maturing individuals were larger than late-maturing ones, suggesting that both sexes exhibit some plasticity in their developmental trajectories. Such plasticity indicates that protandry could co-occur with any degree and direction of SSD. Our calculation of the probability of mating success along the season shows multiple male maturation time points with similar predicted mating success. This suggests that males follow multiple strategies with equal success, trading-off access to virgin females with intensity of male–male competition. Our results challenge classic hypotheses linking protandry and female-biased SSD, and emphasize the importance of directly testing the often-assumed relationships between co-occurring animal traits

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation

Different Host Exploitation Strategies in Two Zebra Mussel-Trematode Systems: Adjustments of Host Life History Traits

The zebra mussel is the intermediate host for two digenean trematodes, Phyllodistomum folium and Bucephalus polymorphus, infecting gills and the gonad respectively. Many gray areas exist relating to the host physiological disturbances associated with these infections, and the strategies used by these parasites to exploit their host without killing it. The aim of this study was to examine the host exploitation strategies of these trematodes and the associated host physiological disturbances. We hypothesized that these two parasite species, by infecting two different organs (gills or gonads), do not induce the same physiological changes. Four cellular responses (lysosomal and peroxisomal defence systems, lipidic peroxidation and lipidic reserves) in the host digestive gland were studied by histochemistry and stereology, as well as the energetic reserves available in gonads. Moreover, two indices were calculated related to the reproductive status and the physiological condition of the organisms. Both parasites induced adjustments of zebra mussel life history traits. The host-exploitation strategy adopted by P. folium would occur during a short-term period due to gill deformation, and could be defined as “virulent.” Moreover, this parasite had significant host gender-dependent effects: infected males displayed a slowed-down metabolism and energetic reserves more allocated to growth, whereas females displayed better defences and would allocate more energy to reproduction and maintenance. In contrast, B. polymorphus would be a more “prudent” parasite, exploiting its host during a long-term period through the consumption of reserves allocated to reproduction

Parasites of non-native freshwater fishes introduced into england and wales suggest enemy release and parasite acquisition

When non-native species are introduced into a new range, their parasites can also be introduced, with these potentially spilling-over into native hosts. However, in general, evidence suggests that a high proportion of their native parasites are lost during introduction and infections by some new parasites from the native range might occur, potentially resulting in parasite spill-back to native species. These processes were investigated here using parasite surveys and literature review on seven non-native freshwater fishes introduced into England and Wales. Comparison of the mean numbers of parasite species and genera per population for each fish species England andWaleswith their native ranges revealed\9 % of the native parasite fauna were present in their populations in England and Wales. There was no evidence suggesting these introduced parasites had spilled over into sympatric native fishes. The non-native fishes did acquire parasites following their introduction, providing potential for parasite spill-back to sympatric fishes, and resulted in non-significant differences in overall mean numbers of parasites per populations between the two ranges. Through this acquisition, the non-native fishes also had mean numbers of parasite species and genera per population that were not significantly different to sympatric native fishes. Thus, the non-native fishes in England and Wales showed evidence of enemy release, acquired new parasites following introduction providing potential for spill-back, but showed no evidence of parasite spill-over

Diversity, Loss, and Gain of Malaria Parasites in a Globally Invasive Bird

Invasive species can displace natives, and thus identifying the traits that make aliens successful is crucial for predicting and preventing biodiversity loss. Pathogens may play an important role in the invasive process, facilitating colonization of their hosts in new continents and islands. According to the Novel Weapon Hypothesis, colonizers may out-compete local native species by bringing with them novel pathogens to which native species are not adapted. In contrast, the Enemy Release Hypothesis suggests that flourishing colonizers are successful because they have left their pathogens behind. To assess the role of avian malaria and related haemosporidian parasites in the global spread of a common invasive bird, we examined the prevalence and genetic diversity of haemosporidian parasites (order Haemosporida, genera Plasmodium and Haemoproteus) infecting house sparrows (Passer domesticus). We sampled house sparrows (N = 1820) from 58 locations on 6 continents. All the samples were tested using PCR-based methods; blood films from the PCR-positive birds were examined microscopically to identify parasite species. The results show that haemosporidian parasites in the house sparrows' native range are replaced by species from local host-generalist parasite fauna in the alien environments of North and South America. Furthermore, sparrows in colonized regions displayed a lower diversity and prevalence of parasite infections. Because the house sparrow lost its native parasites when colonizing the American continents, the release from these natural enemies may have facilitated its invasion in the last two centuries. Our findings therefore reject the Novel Weapon Hypothesis and are concordant with the Enemy Release Hypothesis