Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicum in 50 irrigated and rain-fed villages in Samar Province, the Philippines

BACKGROUND: Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines. METHODS: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis. RESULTS: A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21). DISCUSSION: We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants

Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease, lymphatic filariasis

<p>Abstract</p> <p>Background</p> <p>Large-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variability</p> <p>Results</p> <p>We show that parameters of density-dependent functions relating to immunity, parasite establishment, as well as parasite aggregation, varied significantly between the nine different settings, contributing to locally varying filarial elimination thresholds. Parasite elimination thresholds predicted for the settings in which the mosquito vector is anopheline were, however, found to be higher than those in which the mosquito is culicine, substantiating our previous theoretical findings. The results also indicate that the probability that the parasite will be eliminated following six rounds of Mass Drug Administration with diethylcarbamazine and albendazole decreases markedly but non-linearly as the annual biting rate and parasite reproduction number increases.</p> <p>Conclusions</p> <p>This paper shows that specific ecological conditions in a community can lead to significant local differences in population dynamics and, consequently, elimination threshold estimates for lymphatic filariasis. These findings, and the difficulty of measuring the key local parameters (infection aggregation and acquired immunity) governing differences in transmission thresholds between communities, mean that it is necessary for us to rethink the utility of the current anticipatory approaches for achieving the elimination of filariasis both locally and globally.</p

Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy

Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach

Background: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers

Evaluation of a reproductive health awareness program for adolescence in urban Tanzania-A quasi-experimental pre-test post-test research

Sub-Saharan Africa is among the countries where 10% of girls become mothers by the age of 16 years old. The United Republic of Tanzania located in Sub-Saharan Africa is one country where teenage pregnancy is a problem facing adolescent girls. Adolescent pregnancy has been identified as one of the reasons for girls dropping out from school. This study's purpose was to evaluate a reproductive health awareness program for the improvement of reproductive health for adolescents in urban Tanzania. A quasi-experimental pre-test and post-test research design was conducted to evaluate adolescents' knowledge, attitude, and behavior about reproductive health before and after the program. Data were collected from students aged 11 to 16, at Ilala Municipal, Dar es Salaam, Tanzania. An anonymous 23-item questionnaire provided the data. The program was conducted using a picture drama, reproductive health materials and group discussion. In total, 313 questionnaires were distributed and 305 (97.4%) were useable for the final analysis. The mean age for girls was 12.5 years and 13.2 years for boys. A large minority of both girls (26.8%) and boys (41.4%) had experienced sex and among the girls who had experienced sex, 51.2% reported that it was by force. The girls' mean score in the knowledge pre-test was 5.9, and 6.8 in post-test, which increased significantly (t=7.9, p=0.000). The mean behavior pre-test score was 25.8 and post-test was 26.6, which showed a significant increase (t=3.0, p=0.003). The boys' mean score in the knowledge pre-test was 6.4 and 7.0 for the post-test, which increased significantly (t=4.5, p=0.000). The mean behavior pre-test score was 25.6 and 26.4 in post-test, which showed a significant increase (t=2.4, p=0.019). However, the pre-test and post-test attitude scores showed no statistically significant difference for either girls or boys. Teenagers have sexual experiences including sexual violence. Both of these phenomena are prevalent among school-going adolescents. The reproductive health program improved the students' knowledge and behavior about sexuality and decision-making after the program for both girls and boys. However, their attitudes about reproductive health were not likely to change based on the educational intervention as designed for this study

Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats

Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a “gateway” drug that sensitizes reward pathways to the addictive effects of other psychostimulants. To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06&nbsp;mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0&nbsp;mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3&nbsp;days with saline or cocaine (0.4&nbsp;mg/kg, i.v.), and, after 1&nbsp;day of withdrawal, were given a challenge dose of cocaine (0.4&nbsp;mg/kg, i.v.). Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2–4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats

Wind, Waves, and Wing Loading: Morphological Specialization May Limit Range Expansion of Endangered Albatrosses

Among the varied adaptations for avian flight, the morphological traits allowing large-bodied albatrosses to capitalize on wind and wave energy for efficient long-distance flight are unparalleled. Consequently, the biogeographic distribution of most albatrosses is limited to the windiest oceanic regions on earth; however, exceptions exist. Species breeding in the North and Central Pacific Ocean (Phoebastria spp.) inhabit regions of lower wind speed and wave height than southern hemisphere genera, and have large intrageneric variation in body size and aerodynamic performance. Here, we test the hypothesis that regional wind and wave regimes explain observed differences in Phoebastria albatross morphology and we compare their aerodynamic performance to representatives from the other three genera of this globally distributed avian family. In the North and Central Pacific, two species (short-tailed P. albatrus and waved P. irrorata) are markedly larger, yet have the smallest breeding ranges near highly productive coastal upwelling systems. Short-tailed albatrosses, however, have 60% higher wing loading (weight per area of lift) compared to waved albatrosses. Indeed, calculated aerodynamic performance of waved albatrosses, the only tropical albatross species, is more similar to those of their smaller congeners (black-footed P. nigripes and Laysan P. immutabilis), which have relatively low wing loading and much larger foraging ranges that include central oceanic gyres of relatively low productivity. Globally, the aerodynamic performance of short-tailed and waved albatrosses are most anomalous for their body sizes, yet consistent with wind regimes within their breeding season foraging ranges. Our results are the first to integrate global wind and wave patterns with albatross aerodynamics, thereby identifying morphological specialization that may explain limited breeding ranges of two endangered albatross species. These results are further relevant to understanding past and potentially predicting future distributional limits of albatrosses globally, particularly with respect to climate change effects on basin-scale and regional wind fields