Hematological Changes in Women and Infants Exposed to an AZT-Containing Regimen for Prevention of Mother-to-child-transmission of HIV in Tanzania.

Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1-4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants. A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4-6 and 12. For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4-6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2. AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

The method of educational assessment affects children’s neural processing and performance: behavioural and fMRI Evidence.

Standardised educational assessments are now widespread, yet their development has given comparatively more consideration to what to assess than how to optimally assess students’ competencies. Existing evidence from behavioural studies with children and neuroscience studies with adults suggest that the method of assessment may affect neural processing and performance, but current evidence remains limited. To investigate the impact of assessment methods on neural processing and performance in young children, we used functional magnetic resonance imaging to identify and quantify the neural correlates during performance across a range of current approaches to standardised spelling assessment. Results indicated that children’s test performance declined as the cognitive load of assessment method increased. Activation of neural nodes associated with working memory further suggests that this performance decline may be a consequence of a higher cognitive load, rather than the complexity of the content. These findings provide insights into principles of assessment (re)design, to ensure assessment results are an accurate reflection of students’ true levels of competency

Virtual environments as memory training devices in navigational tasks for older adults.

Cognitive training approaches using virtual environments (VEs) might counter age-related visuospatial memory decline and associated difficulties in wayfinding. However, the effects of the visual design of a VE in route learning are not fully understood. Therefore, we created a custom-designed VE optimized for route learning, with adjusted levels of realism and highlighted landmark locations (MixedVE). Herein we tested participants' route recall performance in identifying direction of turn at the intersection with this MixedVE against two baseline alternatives (AbstractVE, RealisticVE). An older vs. a younger group solved the tasks in two stages (immediate vs. delayed recall by one week). Our results demonstrate that the MixedVE facilitates better recall accuracy than the other two VEs for both age groups. Importantly, this pattern persists a week later. Additionally, our older participants were mostly overconfident in their route recall performance, but the MixedVE moderated this potentially detrimental overconfidence. Before the experiment, participants clearly preferred the RealisticVE, whereas after the experiment, most of the younger, and many of the older participants, preferred the MixedVE. Taken together, our findings provide insights into the importance of tailoring visualization design in route learning with VEs. Furthermore, we demonstrate the great potential of the MixedVE and by extension, of similar VEs as memory training devices for route learning, especially for older participants

Beat synchronization across the lifespan: intersection of development and musical experience

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample

Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC

Sex Pheromone Evolution Is Associated with Differential Regulation of the Same Desaturase Gene in Two Genera of Leafroller Moths

Chemical signals are prevalent in sexual communication systems. Mate recognition has been extensively studied within the Lepidoptera, where the production and recognition of species-specific sex pheromone signals are typically the defining character. While the specific blend of compounds that makes up the sex pheromones of many species has been characterized, the molecular mechanisms underpinning the evolution of pheromone-based mate recognition systems remain largely unknown. We have focused on two sets of sibling species within the leafroller moth genera Ctenopseustis and Planotortrix that have rapidly evolved the use of distinct sex pheromone blends. The compounds within these blends differ almost exclusively in the relative position of double bonds that are introduced by desaturase enzymes. Of the six desaturase orthologs isolated from all four species, functional analyses in yeast and gene expression in pheromone glands implicate three in pheromone biosynthesis, two Δ9-desaturases, and a Δ10-desaturase, while the remaining three desaturases include a Δ6-desaturase, a terminal desaturase, and a non-functional desaturase. Comparative quantitative real-time PCR reveals that the Δ10-desaturase is differentially expressed in the pheromone glands of the two sets of sibling species, consistent with differences in the pheromone blend in both species pairs. In the pheromone glands of species that utilize (Z)-8-tetradecenyl acetate as sex pheromone component (Ctenopseustis obliquana and Planotortrix octo), the expression levels of the Δ10-desaturase are significantly higher than in the pheromone glands of their respective sibling species (C. herana and P. excessana). Our results demonstrate that interspecific sex pheromone differences are associated with differential regulation of the same desaturase gene in two genera of moths. We suggest that differential gene regulation among members of a multigene family may be an important mechanism of molecular innovation in sex pheromone evolution and speciation

Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines