Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Urinary schistosomiasis among preschool-aged children in Sahelian rural communities in Mali

<p>Abstract</p> <p>Background</p> <p>Mass chemotherapy with praziquantel is the main control strategy for schistosomiasis in Mali. However, in the national control programme for schistosomiasis and soil-transmitted helminthiasis, infants and preschool-aged children are overlooked in preventive chemotherapy campaigns. We therefore determined the prevalence and intensity of urinary schistosomiasis in children between the ages 1-4 years in three villages across Diema health district, a rural community with endemic schistosomiasis in Mali. For <it>Schistosoma haematobium </it>diagnosis, a single urine sample of 10 ml obtained from each child was subjected to the standard urine filtration method.</p> <p>Results</p> <p>Of the 338 children examined 173 (51.2%) were infected. Both prevalence and intensity of infection varied significantly between communities (p < 0.01). There was no significant difference (p = 0.94) in infection rates between boys (51.2%) and girls (50.3%). Likewise, prevalence did not significantly increase with age (p = 0.86). The overall geometric mean of Williams (GMw) was 18.41 eggs/10 ml urine, with no significant association (p = 0.91) between boys (17.48 eggs/10 ml urine) and girls (19.69 eggs/10 ml urine). However, the GMw significantly increased with age (p = 0.04). Infection of preschool children would occur through early exposure to infected water bodies through both passive and active process.</p> <p>Conclusion</p> <p>Our study showed that preschool children living closely to lakes across in Mali are at high risk to be infected by schistosomiasis and contributed largely to the transmission; therefore schistosomiasis control interventions should also target infants in addition to school children and adults in endemic areas.</p

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trial

Background: Low n-3 polyunsaturated fatty acids (PUFAs) has been linked to depression, but the preventive effect of n-3PUFAs supplementation on maternal depression needs further investigation. We aimed to evaluate the efficacy of a daily dose of n-3 PUFAs supplementation (fish oil) on the prevention of postpartum depression (PPD). Methods: A randomized, placebo-controlled, double blind trial was designed and nested into a cohort study conducted in Rio de Janeiro, Brazil. Sixty pregnant women identified as being at risk for PPD were invited and randomly assigned to receive fish oil capsules [1.8 g (1.08 g of Eicosapentaenoic (EPA) and 0.72 g of Docosapentaenoic (DHA) acids)] or placebo (control). The Edinburgh Postnatal Depression Scale (EPDS) was scored at 5–13 (T0, baseline), 22–24 (T1), 30–32 weeks of gestation (T2) and 4–6 weeks’ postpartum (T3). Supplementation started at week 22–24 of gestation (T1) and lasted for 16 weeks. Serum fatty acids were assayed to evaluate compliance. Prevalence of EPDS ≥11 was the primary outcome, and mean and changes in EPDS score, length of gestation, and birth weight the secondary outcomes. Linear mixed-effect (LME) and random-intercept logistic regression models were performed to test the effect of fish oil supplementation on prevalence of EPDS ≥11 and EPDS scores variation. Results: In intention-to-treat (ITT) analysis, at 30–32 weeks’ gestation women in the fish oil presented higher serum concentration of EPA, DHA and lower n-6/n-3 ratio comparing to the control group. There were no differences between intervention and control groups in the prevalence of EPDS ≥11, EPDS scores over time, or in changes in EPDS scores from pregnancy to postpartum in either the ITT or per-protocol analyses. Women in the fish oil group with previous history of depression presented a higher reduction on the EPDS score from the second to the third trimester in the fish oil comparing to the control group in the ITT analyses [−1.0 (−3.0–0.0) vs. -0.0 (−1.0–3.0), P = 0.038). These results were confirmed on the LME model (β = −3.441; 95%CI: -6.532– -0.350, P = 0.029). Conclusion: Daily supplementation of 1.8 g of n-3 PUFAs during 16 weeks did not prevent maternal depressive symptoms in a sample of Brazilian women

“Bibliostory—Educational Comic Stories.” A Social Constructivist Approach to Media and Information Literacy Education for Children and Adolescents

Our paper presents a theoretical background for a Polish comic book “Bibliostory—educational comic stories” (Pl. Bibliostory—edukacyjne historie komiksowe). The comic targets children between 9 and 12 years of age and youths from 13 to 16 years of age. Each story illustrates one issue, such as information searching, organization of information, plagiarism, and information problem solving strategy. Bibliostory is based on two constructivist pedagogical concepts: the zone of proximal development (ZPD) and case-based learning/teaching. These concepts, on application level, are first of all associated with designing educational situations and relationships between teachers and students (educators and learners). The aim of our paper is to present the possibilities of application of these concepts in the educational comic books. We describe the general assumptions of two concepts, then we focus on elements applied in Bibliostory project. We also provide a review of literature on the educational potential of comic books.Zuza Wiorogórska’s work was carried out during her stay as the visiting scholar at the University of California, Berkeley, thanks to a scholarship from the Kosciuszko Foundation. Ewa Rozkosz’s work was carried out thanks to the grant awarded by the Faculty of Education of the University of Lower Silesia for the project “Społeczno-kulturowe podejście w projektowaniu materiałów edukacyjnych na potrzeby edukacji medialnej I inforamacyjnej dzieci i młodzieży na przykładzie »Bibliostory«” (nr 05/ WGW/dok/2016)

Binge-Pattern Alcohol Exposure during Puberty Induces Long-Term Changes in HPA Axis Reactivity

Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH) treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis, as manifested by alterations in corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP), and corticosterone (CORT) during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis