The significance of human cytomegalovirus infection in healthy blood donors

Human cytomegalovirus (HCMV) infection has been studied in blood donors. The subsequent establishment of latency by the virus is a significant factor in blood transfusion practice as the latent virus may be transmitted by transfusion to susceptible patients with serious consequences. The current prevalence of HCMV-IgG in the donor population was found to be 47% and related to donor age and sex; increasing with age and significantly higher in females (p < 0.001). The prevalence of HCMV-IgM and -IgA in the donor population was determined in an attempt to identify recently infected donors, purported to give rise to an increased incidence of HCMV transmission. They were detected in 0 09% and 1-5% of donors respectively; no other indications of recent infection were detected. The immune response to HCMV was found to be stable with respect to Ab titre and immunoblotting profiles. The current seroconversion rate of HCMV-Ab negative donors was found to be approximately half of that expected. To identify acutely infected donors and to confirm the presumed sites of latency, studies were performed using conventional and molecular techniques to detect either infectious virus or viral nucleic acid in donated blood or saliva and urine samples obtained from donors. HCMV nucleic acid was not detected in serum or leucocytes by dot-blot hybridisation, although HCMV DNA and IE RNA were demonstrated in leucocytes using the PCR technique. Urine from one seropositive donor was found to contain detectable HCMV by cell culture and PCR. No saliva samples were found to contain HCMV. Although HCMV can be detected in healthy donors using molecular techniques, HCMV-Ab screening remains the most appropriate method for determining those donations likely to transmit HCMV

Role of smartphone-driven virtual reality field trips in inquiry-based learning

A Google Expedition (GE) is a Virtual Reality approach comprising of 360 degree photospheres of a location (e.g. a museum, or a city like Rio de Janeiro, an active volcano) along with the description of location, points of interest and suggested questions for discussion. Using a Tablet and via the GEs App, a teacher can guide students. Students experience the GE through the smartphones embedded within the VR viewers called Google cardboard. Our research project’s objective is examine the potential role of Virtual Reality (VR) in science and geography in schools. In this research paper, we will discuss the results of our empirical investigations for one of the research questions: whether VR-based guided field trips via GEs can support self-directed inquiry-based learning (IBL). Our investigations on IBL have involved: conducting Geography lessons using one or more GEs at KS3 and KS4 stages; analysis of the lesson-observations; and assessment of the nature of questions that are generated by the students during these lessons. The teachers reported that the students generate more questions (than usual) in lessons that involve GEs/VR. Also, the questions are high-order and have one of more of the following features: are analytical, enquire about impact, or are evaluative

Oxygen Isotope Variations in Recent Magnesian Lavas from Iceland’s Northern Neovolcanic Zone

Geochemical variations of Icelandic lavas reflect both differences in the compositions and conditions and extents of melting of their sources (e.g., Thirlwall, 1994) and magmatic differentiation and crustal contamination (e.g., Gee et al., 1996). Discriminating between these two processes is key to constructing models of the composition and dynamics of the Iceland plume. Recent efforts to do so have focused on relatively magnesian lavas from the northern and western neovolcanic zones; Theistareykir volcano has been of particular importance for this work because of its abundance of magnesian lavas, the absence of a well-developed central volcanic complex, and the fact that it's lavas include the 'depleted' extreme to the array of compositional variations in Icelandic lavas generally (e.g., Elliott et al., 1991). We report here a study of oxygen-isotope variations in phenocrysts from recent Theistareykir lavas, conducted to search for evidence for both crustal contamination and oxygen isotope variations in the sub-Icelandic mantle

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

Transgenic mice overexpressing the high mobility group A (HMGA) genes, Hmga1 or Hmga2 develop pituitary tumours and their overexpression is also a frequent finding in human pituitary adenomas. In some cases, increased expression of HMGA2 but not that of HMGA1 is consequent to genetic perturbations. However, recent studies show that down-regulation of microRNA (miRNA), that contemporaneously target the HMGA1 and HMGA2 transcripts, are associated with their overexpression. In a cohort of primary pituitary adenoma we determine the impact of epigenetic modifications on the expression of HMGA-targeting miRNA. For these miRNAs, chromatin immunoprecipitations showed that transcript down-regulation is correlated with histone tail modifications associated with condensed silenced genes. The functional impact of epigenetic modification on miRNA expression was determined in the rodent pituitary cell line, GH3. In these cells, histone tail, miRNA-associated, modifications were similar to those apparent in human adenoma and likely account for their repression. Indeed, challenge of GH3 cells with the epidrugs, zebularine and TSA, led to enrichment of the histone modification, H3K9Ac, associated with active genes, and depletion of the modification, H3K27me3, associated with silent genes and re-expression of HMGA-targeting miRNA. Moreover, epidrugs challenges were also associated with a concomitant decrease in hmga1 transcript and protein levels and concurrent increase in bmp-4 expression. These findings show that the inverse relationship between HMGA expression and targeting miRNA is reversible through epidrug interventions. In addition to showing a mechanistic link between epigenetic modifications and miRNA expression these findings underscore their potential as therapeutic targets in this and other diseases

Dynamics of direct inter-pack encounters in endangered African wild dogs

Aggressive encounters may have important life history consequences due to the potential for injury and death, disease transmission, dispersal opportunities or exclusion from key areas of the home range. Despite this, little is known of their detailed dynamics, mainly due to the difficulties of directly observing encounters in detail. Here, we describe detailed spatial dynamics of inter-pack encounters in African wild dogs (Lycaon pictus), using data from custom-built high-resolution GPS collars in 11 free-ranging packs. On average, each pack encountered another pack approximately every 7 weeks and met each neighbour twice each year. Surprisingly, intruders were more likely to win encounters (winning 78.6% of encounters by remaining closer to the site in the short term). However, intruders did tend to move farther than residents toward their own range core in the short-term (1 h) post-encounter, and if this were used to indicate losing an encounter, then the majority (73.3%) of encounters were won by residents. Surprisingly, relative pack size had little effect on encounter outcome, and injuries were rare (<15% of encounters). These results highlight the difficulty of remotely scoring encounters involving mobile participants away from static defendable food resources. Although inter-pack range overlap was reduced following an encounter, encounter outcome did not seem to drive this, as both packs shifted their ranges post-encounter. Our results indicate that inter-pack encounters may be lower risk than previously suggested and do not appear to influence long-term movement and ranging

Engineering Antigen-Specific T Cells from Genetically Modified Human Hematopoietic Stem Cells in Immunodeficient Mice

There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, “transgenic” human anti-HIV T cell receptor (TCR). Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control

Establishment of the 1st World Health Organization International Standard for Plasmodium falciparum DNA for nucleic acid amplification technique (NAT)-based assays

BACKGROUND: In order to harmonize results for the detection and quantification of Plasmodium falciparum DNA by nucleic acid amplification technique (NAT)-based assays, a World Health Organization (WHO) collaborative study was performed, evaluating a series of candidate standard preparations. METHODS: Fourteen laboratories from 10 different countries participated in the collaborative study. Four candidate preparations based upon blood samples parasitaemic for P. falciparum were evaluated in the study. Sample AA was lyophilized, whilst samples BB, CC and DD were liquid/frozen preparations. The candidate standards were tested by each laboratory at a range of dilutions in four independent assays, using both qualitative and quantitative NAT-based assays. The results were collated and analysed statistically. RESULTS: Twenty sets of data were returned from the participating laboratories and used to determine the mean P. falciparum DNA content for each sample. The mean log10 "equivalents"/ml were 8.51 for sample AA, 8.45 for sample BB, 8.35 for sample CC, and 5.51 for sample DD. The freeze-dried preparation AA, was examined by accelerated thermal degradation studies and found to be highly stable. CONCLUSION: On the basis of the collaborative study, the freeze-dried material, AA (NIBSC code No. 04/176) was established as the 1st WHO International Standard for P. falciparum DNA NAT-based assays and has been assigned a potency of 10(9) International Units (IU) per ml. Each vial contains 5 x 10(8) IU, equivalent to 0.5 ml of material after reconstitution

Treatment-Mediated Alterations in HIV Fitness Preserve CD4+ T Cell Counts but Have Minimal Effects on Viral Load

For most HIV-infected patients, antiretroviral therapy controls viral replication. However, in some patients drug resistance can cause therapy to fail. Nonetheless, continued therapy with a failing regimen can preserve or even lead to increases in CD4+ T cell counts. To understand the biological basis of these observations, we used mathematical models to explain observations made in patients with drug-resistant HIV treated with enfuvirtide (ENF/T-20), an HIV-1 fusion inhibitor. Due to resistance emergence, ENF was removed from the drug regimen, drug-sensitive virus regrown, and ENF was re-administered. We used our model to study the dynamics of plasma-viral RNA and CD4+ T cell levels, and the competition between drug-sensitive and resistant viruses during therapy interruption and re-administration. Focusing on resistant viruses carrying the V38A mutation in gp41, we found ENF-resistant virus to be 17±3% less fit than ENF-sensitive virus in the absence of the drug, and that the loss of resistant virus during therapy interruption was primarily due to this fitness cost. Using viral dynamic parameters estimated from these patients, we show that although re-administration of ENF cannot suppress viral load, it can, in the presence of resistant virus, increase CD4+ T cell counts, which should yield clinical benefits. This study provides a framework to investigate HIV and T cell dynamics in patients who develop drug resistance to other antiretroviral agents and may help to develop more effective strategies for treatment