microRNAs of parasitic helminths – identification, characterization and potential as drug targets

microRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. They were first identified in the free-living nematode Caenorhabditis elegans, where the miRNAs lin-4 and let-7 were shown to be essential for regulating correct developmental progression. The sequence of let-7 was subsequently found to be conserved in higher organisms and changes in expression of let-7, as well as other miRNAs, are associated with certain cancers, indicating important regulatory roles. Some miRNAs have been shown to have essential functions, but the roles of many are currently unknown. With the increasing availability of genome sequence data, miRNAs have now been identified from a number of parasitic helminths, by deep sequencing of small RNA libraries and bioinformatic approaches. While some miRNAs are widely conserved in a range of organisms, others are helminth-specific and many are novel to each species. Here we review the potential roles of miRNAs in regulating helminth development, in interacting with the host environment and in development of drug resistance. Use of fluorescently-labeled small RNAs demonstrates uptake by parasites, at least in vitro. Therefore delivery of miRNA inhibitors or mimics has potential to alter miRNA activity, providing a useful tool for probing the roles of miRNAs and suggesting novel routes to therapeutics for parasite control

Occupier Satisfaction and Investment Returns from UK Commercial Real Estate

Purpose The purpose of this paper is to investigate the relationship between occupiers’ satisfaction with the property management service they receive and the financial performance of commercial real estate. Design/methodology/approach The study uses occupier satisfaction data for 240 UK commercial properties collected over a 12-year period and the annual total returns achieved by those properties. Various statistical techniques are employed to assess whether increasing occupier satisfaction leads to greater returns for investors. These include comparing excess returns and risk-adjusted returns with occupier satisfaction at each property to assess whether superior property management generates outperformance (“positive alpha”). The study also investigates whether the relationship between occupier satisfaction and returns is the same across all sectors and whether it is affected by market conditions. Findings A positive correspondence is found between benchmark outperformance and occupier satisfaction. The relationship is similar for all sectors of commercial property and is particularly strong during the Global Financial Crisis, indicating that paying attention to satisfying the needs of occupiers has particular benefits during periods when the supply of commercial real estate exceeds demand. Research limitations/implications The sample of properties was restricted to those for which occupier satisfaction data had been collected by RealService Ltd and whose owners permitted access to the financial performance results. This meant that the properties belong to only three landlords, all UK REITs that care sufficiently about occupier satisfaction to commission studies. Thus the findings might not apply to all commercial properties. The mechanism by which the positive relationship between satisfaction and financial performance occurs is not tested, but the conventional mechanisms of reputation and customer loyalty (the “service-profit chain”) are discussed. Practical implications The findings suggest that it is worthwhile for landlords, or property managers acting on their behalf, to understand the needs of their occupiers in order to deliver the level of service that those occupiers desire. Leases in the UK are generally “triple net” and the total returns used for this analysis are net of property management costs, so the positive relationship between satisfaction and performance is not the result of economising on service delivery. A further implication is that valuers should take more account of occupier satisfaction when assessing the capital value of a property, from which total returns are assessed. Originality/value Demonstrating the links between customer service, customer satisfaction and business profitability is rarely attempted because of the many confounding factors that affect profitability. UK listed real estate companies are typically reluctant to reveal the financial performance of individual properties, and information about occupiers’ satisfaction is not generally available. The authors were fortunate to be granted access to a time series of such data, and to be able to demonstrate that attention to delivering a property management service that satisfies occupiers is likely to bring financial rewards to the owners of the property

Application of small RNA technology for improved control of parasitic helminths

Over the last decade microRNAs (miRNAs) and small interfering RNAs (siRNAs) have emerged as important regulators of post-transcriptional gene expression. miRNAs are short, non-coding RNAs that regulate a variety of processes including cancer, organ development and immune function. This class of small RNAs bind with partial complementarity to their target mRNA sequences, most often in the 3′UTR, to negatively regulate gene expression. In parasitic helminths, miRNAs are being increasingly studied for their potential roles in development and host-parasite interactions. The availability of genome data, combined with small RNA sequencing, has paved the way to profile miRNAs expressed at particular developmental stages for many parasitic helminths. While some miRNAs are conserved across species, others appear to be unique to specific parasites, suggesting important roles in adaptation and survival in the host environment. Some miRNAs are released from parasites, in exosomes or in protein complexes, and the potential effects of these on host immune function are being increasingly studied. In addition, release of miRNAs from schistosome and filarial parasites into host plasma can be exploited for the development of specific and sensitive diagnostic biomarkers of infection. Interfering with miRNA function, as well as silencing key components of the pathways they regulate, will progress our understanding of parasite development and provide a novel approach to therapeutic control. RNA interference (RNAi) by siRNAs has proven to be inconsistent in parasitic nematodes. However, the recent successes reported for schistosome and liver fluke RNAi, encourage further efforts to enhance delivery of RNA and improve in vitro culture systems and assays to monitor phenotypic effects in nematodes. These improvements are important for the establishment of reliable functional genomic platforms for novel drug and vaccine development. In this review we focus on the important roles of miRNAs and siRNAs in post-transcriptional gene regulation in veterinary parasitic helminths and the potential value of these in parasite diagnosis and control

Checkerboard Julia Sets for Rational Maps

In this paper, we consider the family of rational maps \F(z) = z^n + \frac{\la}{z^d}, where $n \geq 2$, $d\geq 1$, and\la \in \bbC. We consider the case where \la lies in the main cardioid of one of the $n-1$ principal Mandelbrot sets in these families. We show that the Julia sets of these maps are always homeomorphic. However, two such maps \F and $F_\mu$ are conjugate on these Julia sets only if the parameters at the centers of the given cardioids satisfy \mu = \nu^{j(d+1)}\la or \mu = \nu^{j(d+1)}\bar{\la} where j \in \bbZ and $\nu$ is an $n-1^{\rm st}$ root of unity. We define a dynamical invariant, which we call the minimal rotation number. It determines which of these maps are are conjugate on their Julia sets, and we obtain an exact count of the number of distinct conjugacy classes of maps drawn from these main cardioids.Comment: 25 pages, 14 figures; Changes since March 19 version: added nine figures, fixed one proof, added a section on a group actio

The effect of precipitation and application rate on dicyandiamide persistence and efficiency in two Irish grassland soils

peer-reviewedThe nitrification inhibitor dicyandiamide (DCD) has had variable success in reducing nitrate (NO3-) leaching and nitrous oxide (N2O) emissions from soils receiving nitrogen (N) fertilisers. Factors such as soil type, temperature and moisture have been linked to the variable efficacy of DCD. Since DCD is water soluble it can be leached from the rooting zone where it is intended to inhibit nitrification. Intact soil columns (15 cm diameter by 35 cm long) were taken from luvic gleysol and haplic cambisol grassland sites and placed in growth chambers. DCD was applied at 15 or 30 kg DCD ha-1, with high or low precipitation. Leaching of DCD, mineral N and the residual soil DCD concentrations were determined over eight weeks High precipitation increased DCD in leachate and decreased recovery in soil. A soil x DCD rate interaction was detected for the DCD unaccounted (proxy for degraded DCD). In the cambisol degradation of DCD was high (circa 81%) and unaffected by DCD rate. In contrast DCD degradation in the gleysol was lower and differentially affected by rate, 67 and 46% for the 15 and 30 kg ha-1 treatments, respectively. Differences DCD degradation rates between soils may be related to differences in organic matter content and associated microbiological activity. Variable degradation rates of DCD in soil, unrelated to temperature or moisture, may contribute to varying DCD efficacy. Soil properties should be considered when tailoring DCD strategies for improving nitrogen use efficiency and crop yields, through the reduction of reactive nitrogen loss.This research was financially supported under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Food and the Marine under grants 07519 and 07545

Bifurcations in the Space of Exponential Maps

This article investigates the parameter space of the exponential family $z\mapsto \exp(z)+\kappa$. We prove that the boundary (in \C) of every hyperbolic component is a Jordan arc, as conjectured by Eremenko and Lyubich as well as Baker and Rippon. In fact, we prove the stronger statement that the exponential bifurcation locus is connected in \C, which is an analog of Douady and Hubbard's celebrated theorem that the Mandelbrot set is connected. We show furthermore that $\infty$ is not accessible through any nonhyperbolic ("queer") stable component. The main part of the argument consists of demonstrating a general "Squeezing Lemma", which controls the structure of parameter space near infinity. We also prove a second conjecture of Eremenko and Lyubich concerning bifurcation trees of hyperbolic components.Comment: 29 pages, 3 figures. The main change in the new version is the introduction of Theorem 1.1 on the connectivity of the bifurcation locus, which follows from the results of the original version but was not explicitly stated. Also, some small revisions have been made and references update

Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus

microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV). Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions

Truncated states obtained by iteration

Quantum states of the electromagnetic field are of considerable importance, finding potential application in various areas of physics, as diverse as solid state physics, quantum communication and cosmology. In this paper we introduce the concept of truncated states obtained via iterative processes (TSI) and study its statistical features, making an analogy with dynamical systems theory (DST). As a specific example, we have studied TSI for the doubling and the logistic functions, which are standard functions in studying chaos. TSI for both the doubling and logistic functions exhibit certain similar patterns when their statistical features are compared from the point of view of DST. A general method to engineer TSI in the running-wave domain is employed, which includes the errors due to the nonidealities of detectors and photocounts.Comment: 10 pages, 22 figure

Reversible skew laurent polynomial rings and deformations of poisson automorphisms

A skew Laurent polynomial ring S = R[x(+/- 1); alpha] is reversible if it has a reversing automorphism, that is, an automorphism theta of period 2 that transposes x and x(-1) and restricts to an automorphism gamma of R with gamma = gamma(-1). We study invariants for reversing automorphisms and apply our methods to determine the rings of invariants of reversing automorphisms of the two most familiar examples of simple skew Laurent polynomial rings, namely a localization of the enveloping algebra of the two-dimensional non-abelian solvable Lie algebra and the coordinate ring of the quantum torus, both of which are deformations of Poisson algebras over the base field F. Their reversing automorphisms are deformations of Poisson automorphisms of those Poisson algebras. In each case, the ring of invariants of the Poisson automorphism is the coordinate ring B of a surface in F-3 and the ring of invariants S-theta of the reversing automorphism is a deformation of B and is a factor of a deformation of F[x(1), x(2), x(3)] for a Poisson bracket determined by the appropriate surface