Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection

Over 90% of the world\u27s population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time (P \u3c 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence (P \u3c 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test; r = -0.5589, P = 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral populations is a key step in this process, as is the expansion of intrahost genomic variation during infection. We report full-length EBV genomes sequenced from the blood and oral wash of 10 individuals early in primary infection and during convalescence. Our data demonstrate considerable diversity within the pool of circulating EBV strains, as well as within individual patients. Overall viral diversity decreased from early to persistent infection, particularly in latently infected B cells, which serve as the viral reservoir. Reduction in B cell-associated viral genome diversity coincided with a convergence toward a reference-like EBV genotype. Greater convergence positively correlated with time after infection, suggesting that the reference-like genome is the result of selection

Effect of formant frequency spacing on perceived gender in pre-pubertal children's voices

<div><p>Background</p><p>It is usually possible to identify the sex of a pre-pubertal child from their voice, despite the absence of sex differences in fundamental frequency at these ages. While it has been suggested that the overall spacing between formants (formant frequency spacing - ΔF) is a key component of the expression and perception of sex in children's voices, the effect of its continuous variation on sex and gender attribution has not yet been investigated.</p><p>Methodology/Principal findings</p><p>In the present study we manipulated voice ΔF of eight year olds (two boys and two girls) along continua covering the observed variation of this parameter in pre-pubertal voices, and assessed the effect of this variation on adult ratings of speakers' sex and gender in two separate experiments. In the first experiment (sex identification) adults were asked to categorise the voice as either male or female. The resulting identification function exhibited a gradual slope from male to female voice categories. In the second experiment (gender rating), adults rated the voices on a continuum from “masculine boy” to “feminine girl”, gradually decreasing their masculinity ratings as ΔF increased.</p><p>Conclusions/Significance</p><p>These results indicate that the role of ΔF in voice gender perception, which has been reported in adult voices, extends to pre-pubertal children's voices: variation in ΔF not only affects the perceived sex, but also the perceived masculinity or femininity of the speaker. We discuss the implications of these observations for the expression and perception of gender in children's voices given the absence of anatomical dimorphism in overall vocal tract length before puberty.</p></div

Law of Genome Evolution Direction : Coding Information Quantity Grows

The problem of the directionality of genome evolution is studied. Based on the analysis of C-value paradox and the evolution of genome size we propose that the function-coding information quantity of a genome always grows in the course of evolution through sequence duplication, expansion of code, and gene transfer from outside. The function-coding information quantity of a genome consists of two parts, p-coding information quantity which encodes functional protein and n-coding information quantity which encodes other functional elements except amino acid sequence. The evidences on the evolutionary law about the function-coding information quantity are listed. The needs of function is the motive force for the expansion of coding information quantity and the information quantity expansion is the way to make functional innovation and extension for a species. So, the increase of coding information quantity of a genome is a measure of the acquired new function and it determines the directionality of genome evolution.Comment: 16 page

Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements

Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also identified a new looping interaction in K562 cells between the beta-globin Locus Control Region and the gamma-beta-globin intergenic region. Interestingly, this region has been implicated in the control of developmental globin gene switching. 5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure

Cultivated Vaginal Microbiomes Alter HIV-1 Infection and Antiretroviral Efficacy in Colonized Epithelial Multilayer Cultures

There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral

ADC Histograms from Routine DWI for Longitudinal Studies in Cerebral Small Vessel Disease: A Field Study in CADASIL.

Diffusion tensor imaging (DTI) histogram metrics are correlated with clinical parameters in cerebral small vessel diseases (cSVD). Whether ADC histogram parameters derived from simple diffusion weighted imaging (DWI) can provide relevant markers for long term studies of cSVD remains unknown. CADASIL patients were evaluated by DWI and DTI in a large cohort study overa6-year period. ADC histogram parameters were compared to those derived from mean diffusivity (MD) histograms in 280 patients using intra-class correlation and Bland-Altman plots. Impact of image corrections applied to ADC maps was assessed and a mixed effect model was used for analyzing the effects of scanner upgrades. The results showed that ADC histogram parameters are strongly correlated to MD histogram parameters and that image corrections have only limited influence on these results. Unexpectedly, scanner upgrades were found to have major effects on diffusion measures with DWI or DTI that can be even larger than those related to patients' characteristics. These data support that ADC histograms from daily used DWI can provide relevant parameters for assessing cSVD, but the variability related to scanner upgrades as regularly performed in clinical centers should be determined precisely for longitudinal and multicentric studies using diffusion MRI in cSVD

Diacritics improve comprehension of the Arabic script by providing access to the meanings of heterophonic homographs

The diacritical markers that represent most of the vowels in the Arabic orthography are generally omitted from written texts. Previous research revealed that the absence of diacritics reduces reading comprehension performance even by skilled readers of Arabic. One possible explanation is that many Arabic words become ambiguous when diacritics are missing. Words of this kind are known as heterophonic homographs and are associated with at least two different pronunciations and meanings when written without diacritics. The aim of the two experiments reported in this study was to investigate whether the presence of diacritics improves the comprehension of all written words, or whether the effects are confined to heterophonic homographs. In Experiment 1, adult readers of Arabic were asked to decide whether written words had a living meaning. The materials included heterophonic homographs that had one living and one non-living meaning. Results showed that diacritics significantly increased the accuracy of semantic decisions about ambiguous words but had no effect on the accuracy of decisions about unambiguous words. Consistent results were observed in Experiment 2 where the materials comprised sentences rather than single words. Overall, the findings suggest that diacritics improve the comprehension of heterophonic homographs by facilitating access to semantic representations that would otherwise be difficult to access from print

The influence of 2-hop network density on spoken word recognition

The final publication is available at Springer via http://dx.doi.org/10.3758/s13423-016-1103-9The influence of 2-hop density on spoken word recognition was investigated. 2-hop density measures the density of connections among the phonological neighbors (i.e., 1-hop neighbors) and phonological neighbors of those neighbors (i.e., 2-hop neighbors) of a target word. In both naming and lexical decision tasks, words with low 2-hop density were recognized more quickly than words with high 2-hop density. Because stimuli were selected such that the number of 1-hop and 2-hop neighbors were matched across both sets of words, the results suggest that spoken word recognition is influenced by the amount of connectivity among distant neighbors of the target word—a result that is not easily accommodated by current models of spoken word recognition. A diffusion of activation framework is proposed to account for the present finding

Reply to Guy et al.: Support for a bottleneck in the 2011 Escherichia coli O104:H4 outbreak in Germany

In our paper (1), we analyzed isolates from the Escherichia coli O104:H4 outbreaks in Germany and France in May to July 2011. We concluded that, although the German outbreak was larger, the German isolates represent a clade within the greater diversity of the French outbreak. We proposed several hypotheses to explain these findings, including that the lineage leading to the German outbreak went through a narrow bottleneck that purged diversity. Guy et al. (2) report the genomes of eight additional E. coli O104:H4 isolates sampled from the German outbreak. By focusing on the numbers of SNPs in their samples, they suggest that the German outbreak is more diverse than we reported and is similar to the French outbreak. In fact, Guy et al.’s data (2) strongly support our conclusion that the German outbreak represents a clade within the diversity