Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O'nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strain

Transgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit known pathogens could be greater than the unmodified form. In this study, the ability to develop two human pathogens in these transgenic mosquitoes carrying a homing endonuclease which is expressed in the testes was compared with its nontransgenic siblings. Infections were performed with Plasmodium falciparum (Welch) and o'nyong-nyong virus (ONNV) and the results between the transgenic and nontransgenic sibling females were compared. There was no difference observed with ONNV isolate SG650 in intrathoracic infections or the 50% oral infectious dose measured at 14 d postinfection or in mean body titers. Some significant differences were observed for leg titers at the medium and highest doses for those individuals in which virus titer could be detected. No consistent difference was observed between the transgenic and nontransgenic comparator females in their ability to develop P. falciparum NF54 strain parasites. This particular transgene caused no significant effect in the ability of mosquitoes to become infected by these two pathogens in this genetic background. These results are discussed in the context of risk to human health if these transgenic individuals were present in the environment

Investigating the effects of external fields polarization on the coupling of pure magnetic waves in the human body in very low frequencies

In this paper we studied the effects of external fields' polarization on the coupling of pure magnetic fields into human body. Finite Difference Time Domain (FDTD) method is used to calculate the current densities induced in a 1 cm resolution anatomically based model with proper tissue conductivities. Twenty different tissues have been considered in this investigation and scaled FDTD technique is used to convert the results of computer code run in 15 MHz to low frequencies which are encountered in the vicinity of industrial induction heating and melting devices. It has been found that external magnetic field's orientation due to human body has a pronounced impact on the level of induced currents in different body tissues. This may potentially help developing protecting strategies to mitigate the situations in which workers are exposed to high levels of external magnetic radiation

The fitness of African malaria vectors in the presence and limitation of host behaviour

<p>Background Host responses are important sources of selection upon the host species range of ectoparasites and phytophagous insects. However little is known about the role of host responses in defining the host species range of malaria vectors. This study aimed to estimate the relative importance of host behaviour to the feeding success and fitness of African malaria vectors, and assess its ability to predict their known host species preferences in nature.</p> <p>Methods Paired evaluations of the feeding success and fitness of African vectors Anopheles arabiensis and Anopheles gambiae s.s in the presence and limitation of host behaviour were conducted in a semi-field system (SFS) at Ifakara Health Institute, Tanzania. In one set of trials, mosquitoes were released within the SFS and allowed to forage overnight on a host that was free to exhibit natural behaviour in response to insect biting. In the other, mosquitoes were allowed to feed directly on from the skin surface of immobile hosts. The feeding success and subsequent fitness of vectors under these conditions were investigated on 6 host types (humans, calves, chickens, cows, dogs and goats) to assess whether physical movements of preferred host species (cattle for An. arabiensis, humans for An. gambiae s.s.) were less effective at preventing mosquito bites than those of common alternatives.</p> <p>Results Anopheles arabiensis generally had greater feeding success when applied directly to host skin than when foraging on unrestricted hosts (in five of six host species). However, An. gambiae s.s obtained blood meals from free and restrained hosts with similar success from most host types (four out of six). Overall, the blood meal size, oviposition rate, fecundity and post-feeding survival of mosquito vectors were significantly higher after feeding on hosts free to exhibit behaviour, than those who were immobilized during feeding trials.</p> <p>Conclusions Allowing hosts to move freely during exposure to mosquitoes was associated with moderate reductions in mosquito feeding success, but no detrimental impact to the subsequent fitness of mosquitoes that were able to feed upon them. This suggests that physical defensive behaviours exhibited by common host species including humans do not impose substantial fitness costs on African malaria vectors.</p&gt

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology

Cloning of somatolactin alpha, beta forms and the somatolactin receptor in Atlantic salmon: Seasonal expression profile in pituitary and ovary of maturing female broodstock

<p>Abstract</p> <p>Background</p> <p>Somatolactin (Sl) is a fish specific adenohypophyseal peptide hormone related to growth hormone (Gh). Some species, including salmonids, possess two forms: Sl alpha and Sl beta. The somatolactin receptor (slr) is closely related to the growth hormone receptor (ghr). Sl has been ascribed many physiological functions, including a role in sexual maturation. In order to clarify the role of Sl in the sexual maturation of female Atlantic salmon (Salmo salar), the full length cDNAs of slr, Sl alpha and Sl beta were cloned and their expression was studied throughout a seasonal reproductive cycle using real-time quantitative PCR (RTqPCR).</p> <p>Methods</p> <p>Atlantic salmon Sl alpha, Sl beta and slr cDNAs were cloned using a PCR approach. Gene expression of Sl alpha, SL beta and slr was studied using RTqPCR over a 17 month period encompassing pre-vitellogenesis, vitellogenesis, ovulation and post ovulation in salmon females. Histological examination of ovarian samples allowed for the classification according to the degree of follicle maturation into oil drop, primary, secondary or tertiary yolk stage.</p> <p>Results</p> <p>The mature peptide sequences of Sl alpha, Sl beta and slr are highly similar to previously cloned salmonid forms and contained the typical motifs. Phylogenetic analysis of Atlantic salmon Sl alpha and Sl beta shows that these peptides group into the two Sl clades present in some fish species. The Atlantic salmon slr grouped with salmonid slr amongst so-called type I ghr. An increase in pituitary Sl alpha and Sl beta transcripts before and during spawning, with a decrease post-ovulation, and a constant expression level of ovarian slr were observed. There was also a transient increase in Sl alpha and Sl beta in May prior to transfer from seawater to fresh water and ensuing fasting.</p> <p>Conclusion</p> <p>The up-regulation of Sl alpha and Sl beta during vitellogenesis and spawning, with a subsequent decrease post-ovulation, supports a role for Sl during gonadal growth and spawning. Sl could also be involved in calcium/phosphate mobilization associated with vitellogenesis or have a role in energy homeostasis associated with lipolysis during fasting. The up-regulation of both Sl alpha and Sl beta prior to fasting and freshwater transfer, suggests a role for Sl linked to reproduction that may be independent of the maturation induced fasting.</p

Host Reproductive Phenology Drives Seasonal Patterns of Host Use in Mosquitoes

Seasonal shifts in host use by mosquitoes from birds to mammals drive the timing and intensity of annual epidemics of mosquito-borne viruses, such as West Nile virus, in North America. The biological mechanism underlying these shifts has been a matter of debate, with hypotheses falling into two camps: (1) the shift is driven by changes in host abundance, or (2) the shift is driven by seasonal changes in the foraging behavior of mosquitoes. Here we explored the idea that seasonal changes in host use by mosquitoes are driven by temporal patterns of host reproduction. We investigated the relationship between seasonal patterns of host use by mosquitoes and host reproductive phenology by examining a seven-year dataset of blood meal identifications from a site in Tuskegee National Forest, Alabama USA and data on reproduction from the most commonly utilized endothermic (white-tailed deer, great blue heron, yellow-crowned night heron) and ectothermic (frogs) hosts. Our analysis revealed that feeding on each host peaked during periods of reproductive activity. Specifically, mosquitoes utilized herons in the spring and early summer, during periods of peak nest occupancy, whereas deer were fed upon most during the late summer and fall, the period corresponding to the peak in births for deer. For frogs, however, feeding on early- and late-season breeders paralleled peaks in male vocalization. We demonstrate for the first time that seasonal patterns of host use by mosquitoes track the reproductive phenology of the hosts. Peaks in relative mosquito feeding on each host during reproductive phases are likely the result of increased tolerance and decreased vigilance to attacking mosquitoes by nestlings and brooding adults (avian hosts), quiescent young (avian and mammalian hosts), and mate-seeking males (frogs)

Overview of the VA Quality Enhancement Research Initiative (QUERI) and QUERI theme articles: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Continuing challenges to timely adoption of evidence-based clinical practices in healthcare have generated intense interest in the development and application of new implementation methods and frameworks. These challenges led the United States (U.S.) Department of Veterans Affairs (VA) to create the Quality Enhancement Research Initiative (QUERI) in the late 1990s. QUERI's purpose was to harness VA's health services research expertise and resources in an ongoing system-wide effort to improve the performance of the VA healthcare system and, thus, quality of care for veterans. QUERI in turn created a systematic means of involving VA researchers both in enhancing VA healthcare quality, by implementing evidence-based practices, and in contributing to the continuing development of implementation science.</p> <p>The efforts of VA researchers to improve healthcare delivery practices through QUERI and related initiatives are documented in a growing body of literature. The scientific frameworks and methodological approaches developed and employed by QUERI are less well described. A QUERI Series of articles in <it>Implementation Science </it>will illustrate many of these QUERI tools. This <it>Overview </it>article introduces both QUERI and the Series.</p> <p>Methods</p> <p>The <it>Overview </it>briefly explains the purpose and context of the QUERI Program. It then describes the following: the key operational structure of QUERI Centers, guiding frameworks designed to enhance implementation and related research, QUERI's progress and promise to date, and the Series' general content. QUERI's frameworks include a core set of steps for diagnosing and closing quality gaps and, simultaneously, advancing implementation science. Throughout the paper, the envisioned involvement and activities of VA researchers within QUERI Centers also are highlighted. The Series is then described, illustrating the use of QUERI frameworks and other tools designed to respond to implementation challenges.</p> <p>Conclusion</p> <p>QUERI's simultaneous pursuit of improvement and research goals within a large healthcare system may be unique. However, descriptions of this still-evolving effort, including its conceptual frameworks, methodological approaches, and enabling processes, should have applicability to implementation researchers in a range of health care settings. Thus, the <it>Series </it>is offered as a resource for other implementation research programs and researchers pursuing common goals in improving care and developing the field of implementation science.</p

Finite Element Modeling of Ultrasonic Waves in Viscoelastic Media

Linear viscoelasticity theory offers a minimal framework within which to construct a consistent, linear and causal model of mechanical wave dispersion. The term dispersion is used here to imply temporal wave spreading and amplitude reduction due to absorptive material properties rather than due to geometrical wave spreading. Numerical modeling of wave propagation in absorptive media has been the subject of recent research in such areas as material property measurement [1] [2], seismology [3] [4] [5] and medical ultrasound [6] [7]. Previously, wave attenuation has been included in transient finite element formulations via a constant damping matrix [8] or functionally in terms of a power law relation [9]. The formulation presented here is based on representing the viscoelastic shear and bulk moduli of the medium as either a discrete or continuous spectrum of decaying exponentials [10]. As a first test of the correctness of the viscoelastic finite element formulation, the finite element results for a simple hypothetical medium are compared with an equivalent Laplace-Hankel transform domain solution.</p