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

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

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

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

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

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

Professional excellence: the necessary convergence of psychological variables

O estudo da excelência humana assume essencialmente dois enfoques, um deles acentuando as variáveis psicológicas dos indivíduos e outro enfatizando as aquisições decorrentes da prática ou treino deliberado. Neste artigo procurou-se integrar tais estudos, propondo que o surgimento e a manutenção da excelência pressupõem uma constelação de variáveis psicológicas que vão para além da alta capacidade intelectual. Mais concretamente, descreveu-se um conjunto de variáveis cognitivas, motivacionais e de personalidade, assumidas como relevantes na excelência profissional em diferentes áreas de desempenho e de conhecimento. No seio das variáveis cognitivas e, fazendo uma ponte com as variáveis de personalidade, destaca-se o papel da criatividade para a excelência, reconhecendo a sua particular relevância em algumas áreas de realização profissional.The study of human excellence can be described based on two main approaches focusing either on individuals' psychological variables or on acquisitions by training or deliberate practice. The purpose of this study is to integrate these models based on the assumption that the emergence and maintenance of excellence requires a constellation of fundamental psychological variables that transcend intellectual capacity. More specifically, a set of cognitive, motivational, and personality variables that are considered important for professional excellence in different levels of performance and areas of knowledge were described. Among the cognitive variables and their association with personality variables, it is worth mentioning the significant role of creativity in the pursuit of excellence, recognizing its relevance to specific areas of professional performance.(undefined

A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability

<p>Abstract</p> <p>Background</p> <p>Intellectual disability (ID) is a serious disorder of the central nervous system with a prevalence of 1-3% in a general population. In the past decades, the research focus has been predominantly on X-linked ID (68 loci and 19 genes for non syndromic X linked ID) while for autosomal recessive nonsyndromic ID (NSID) only 30 loci and 6 genes have been reported to date.</p> <p>Methods</p> <p>Genome-wide homozygosity mapping with 500 K Nsp1 array (Affymetrix), CNV analysis, PCR based breakpoint mapping and DNA sequencing was performed to explore the genetic basis of autosomal recessive nonsyndromic ID in a large Pakistani family.</p> <p>Results</p> <p>Data analysis showed linkage at 8p23 locus with common homozygous region between SNPs rs6989820 and rs2237834, spanning a region of 12.494 Mb. The subsequent CNV analysis of the data revealed a homozygous deletion of 170.673 Kb which encompassed the <it>TUSC3 </it>gene.</p> <p>Conclusion</p> <p>We report a novel deletion mutation in <it>TUSC3 </it>gene which is the second gene after <it>TRAPPC9 </it>in which mutation has been identified in more than one family with autosomal recessive NSID. The study will aid in exploring the molecular pathway of cognition.</p

Innate Synchronous Oscillations in Freely-Organized Small Neuronal Circuits

BACKGROUND: Information processing in neuronal networks relies on the network's ability to generate temporal patterns of action potentials. Although the nature of neuronal network activity has been intensively investigated in the past several decades at the individual neuron level, the underlying principles of the collective network activity, such as the synchronization and coordination between neurons, are largely unknown. Here we focus on isolated neuronal clusters in culture and address the following simple, yet fundamental questions: What is the minimal number of cells needed to exhibit collective dynamics? What are the internal temporal characteristics of such dynamics and how do the temporal features of network activity alternate upon crossover from minimal networks to large networks? METHODOLOGY/PRINCIPAL FINDINGS: We used network engineering techniques to induce self-organization of cultured networks into neuronal clusters of different sizes. We found that small clusters made of as few as 40 cells already exhibit spontaneous collective events characterized by innate synchronous network oscillations in the range of 25 to 100 Hz. The oscillation frequency of each network appeared to be independent of cluster size. The duration and rate of the network events scale with cluster size but converge to that of large uniform networks. Finally, the investigation of two coupled clusters revealed clear activity propagation with master/slave asymmetry. CONCLUSIONS/SIGNIFICANCE: The nature of the activity patterns observed in small networks, namely the consistent emergence of similar activity across networks of different size and morphology, suggests that neuronal clusters self-regulate their activity to sustain network bursts with internal oscillatory features. We therefore suggest that clusters of as few as tens of cells can serve as a minimal but sufficient functional network, capable of sustaining oscillatory activity. Interestingly, the frequencies of these oscillations are similar those observed in vivo