Probing Plasmodium falciparum sexual commitment at the single-cell level

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Reducing Adverse Self-Medication Behaviors in Older Adults with Hypertension: Results of an e-health Clinical Efficacy Trial

A randomized controlled efficacy trial targeting older adults with hypertension (age 60 and over) provided an e-health, tailored intervention with the “next generation” of the Personal Education Program (PEP-NG). Eleven primary care practices with advanced practice registered nurse (APRN) providers participated. Participants (N = 160) were randomly assigned by the PEP-NG (accessed via a wireless touchscreen tablet computer) to either control (entailing data collection and four routine APRN visits) or tailored intervention (involving PEP-NG intervention and four focused APRN visits) group. Compared to patients in the control group, patients receiving the PEP-NG e-health intervention achieved significant increases in both self-medication knowledge and self-efficacy measures, with large effect sizes. Among patients not at BP targets upon entry to the study, therapy intensification in controls (increased antihypertensive dose and/or an additional antihypertensive) was significant (p = .001) with an odds ratio of 21.27 in the control compared to the intervention group. Among patients not at BP targets on visit 1, there was a significant declining linear trend in proportion of the intervention group taking NSAIDs 21–31 days/month (p = 0.008). Satisfaction with the PEP-NG and the APRN provider relationship was high in both groups. These results suggest that the PEP-NG e-health intervention in primary care practices is effective in increasing knowledge and self-efficacy, as well as improving behavior regarding adverse self-medication practices among older adults with hypertension

The topology of connections between rat prefrontal, motor and sensory cortices

The connections of prefrontal cortex (PFC) were investigated in the rat brain to determine the order and location of input and output connections to motor and somatosensory cortex. Retrograde (100 nl Fluoro-Gold) and anterograde (100 nl Biotinylated Dextran Amines, BDA; Fluorescein and Texas Red) neuronanatomical tracers were injected into the subdivisions of the PFC (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) and their projections studied. We found clear evidence for organized input projections from the motor and somatosensory cortices to the PFC, with distinct areas of motor and cingulate cortex projecting in an ordered arrangement to the subdivisions of PFC. As injection location of retrograde tracer was moved from medial to lateral in PFC, we observed an ordered arrangement of projections occurring in sensory-motor cortex. There was a significant effect of retrograde injection location on the position of labelled cells occurring in sensory-motor cortex (dorsoventral, anterior-posterior and mediolateral axes p < 0.001). The arrangement of output projections from PFC also displayed a significant ordered projection to sensory-motor cortex (dorsoventral p < 0.001, anterior-posterior p = 0.002 and mediolateral axes p < 0.001)

Інноваційні педагогічні технології в лінгводидактиці вищої школи

Мета статті – описати інноваційні технології, які дають можливості викладачам успішніше керувати навчально-пізнавальною діяльністю студентів у процесі лінгводидактичної підготовки майбутніх вчителів української мови

COIL: a methodology for evaluating malarial complexity of infection using likelihood from single nucleotide polymorphism data.

International audienceComplex malaria infections are defined as those containing more than one genetically distinct lineage of Plasmodium parasite. Complexity of infection (COI) is a useful parameter to estimate from patient blood samples because it is associated with clinical outcome, epidemiology and disease transmission rate. This manuscript describes a method for estimating COI using likelihood, called COIL, from a panel of bi-allelic genotyping assays. COIL assumes that distinct parasite lineages in complex infections are unrelated and that genotyped loci do not exhibit significant linkage disequilibrium. Using the population minor allele frequency (MAF) of the genotyped loci, COIL uses the binomial distribution to estimate the likelihood of a COI level given the prevalence of observed monomorphic or polymorphic genotypes within each sample. COIL reliably estimates COI up to a level of three or five with at least 24 or 96 unlinked genotyped loci, respectively, as determined by in silico simulation and empirical validation. Evaluation of COI levels greater than five in patient samples may require a very large collection of genotype data, making sequencing a more cost-effective approach for evaluating COI under conditions when disease transmission is extremely high. Performance of the method is positively correlated with the MAF of the genotyped loci. COI estimates from existing SNP genotype datasets create a more detailed portrait of disease than analyses based simply on the number of polymorphic genotypes observed within samples. The capacity to reliably estimate COI from a genome-wide panel of SNP genotypes provides a potentially more accurate alternative to methods relying on PCR amplification of a small number of loci for estimating COI. This approach will also increase the number of applications of SNP genotype data, providing additional motivation to employ SNP barcodes for studies of disease epidemiology or control measure efficacy. The COIL program is available for download from GitHub, and users may also upload their SNP genotype data to a web interface for simple and efficient determination of sample COI

Distinct contributions of frontal areas to emotion and social behaviour in the rat

Although the lesions of patients with impaired social behaviour encompass both orbitofrontal and anterior cingulate cortex (OFC and ACC), attempts to model such impairments in animals have focused on the OFC. However, recent neuroimaging attempts to identify the neural correlates of social interaction have emphasized the relative importance of ACC. Here we report the effect of circumscribed excitotoxic lesions of either OFC or ACC on ethological, unconditioned tests of emotion and social behaviour in the Lister hooded rat. OFC lesions altered emotional responsiveness to stimuli in non-social, fear-inducing situations (hyponeophagia test), and produced a small but statistically significant increase in aggression to other rats, but did not compromise other aspects of social interaction and appraisal. ACC lesions did, however, affect the utilization of social information. Specifically, ACC lesions diminished interest in other individuals and caused a relative reduction in memory for social stimuli. Whereas normal animals habituated to repeated presentations of the same individual, the poor performance of ACC animals entailed continued higher levels of responsiveness to repeated presentations of the same individual. The ACC impairment cannot simply be attributed to a general reduction in arousal, or a general impairment in recognition memory. Neither lesion affected anxiety per se (successive alleys test). Further analyses were conducted to investigate whether the changes in aggressive and social behaviour were related to different aspects of decision-making. Although the relationship between changes in social interaction and decision-making after ACC lesions is unclear, OFC impairments in emotionality were correlated with increased impulsive choice

Probing Plasmodium falciparum sexual commitment at the single-cell level [version 3; referees: 2 approved]

Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Evolutionary Mirages: Selection on Binding Site Composition Creates the Illusion of Conserved Grammars in Drosophila Enhancers

The clustering of transcription factor binding sites in developmental enhancers and the apparent preferential conservation of clustered sites have been widely interpreted as proof that spatially constrained physical interactions between transcription factors are required for regulatory function. However, we show here that selection on the composition of enhancers alone, and not their internal structure, leads to the accumulation of clustered sites with evolutionary dynamics that suggest they are preferentially conserved. We simulated the evolution of idealized enhancers from Drosophila melanogaster constrained to contain only a minimum number of binding sites for one or more factors. Under this constraint, mutations that destroy an existing binding site are tolerated only if a compensating site has emerged elsewhere in the enhancer. Overlapping sites, such as those frequently observed for the activator Bicoid and repressor Krüppel, had significantly longer evolutionary half-lives than isolated sites for the same factors. This leads to a substantially higher density of overlapping sites than expected by chance and the appearance that such sites are preferentially conserved. Because D. melanogaster (like many other species) has a bias for deletions over insertions, sites tended to become closer together over time, leading to an overall clustering of sites in the absence of any selection for clustered sites. Since this effect is strongest for the oldest sites, clustered sites also incorrectly appear to be preferentially conserved. Following speciation, sites tend to be closer together in all descendent species than in their common ancestors, violating the common assumption that shared features of species' genomes reflect their ancestral state. Finally, we show that selection on binding site composition alone recapitulates the observed number of overlapping and closely neighboring sites in real D. melanogaster enhancers. Thus, this study calls into question the common practice of inferring “cis-regulatory grammars” from the organization and evolutionary dynamics of developmental enhancers