Auditory object cognition in dementia

The cognition of nonverbal sounds in dementia has been relatively little explored. Here we undertook a systematic study of nonverbal sound processing in patient groups with canonical dementia syndromes comprising clinically diagnosed typical amnestic Alzheimer's disease (AD; n = 21), progressive nonfluent aphasia (PNFA; n = 5), logopenic progressive aphasia (LPA; n = 7) and aphasia in association with a progranulin gene mutation (GAA; n = 1), and in healthy age-matched controls (n = 20). Based on a cognitive framework treating complex sounds as 'auditory objects', we designed a novel neuropsychological battery to probe auditory object cognition at early perceptual (sub-object), object representational (apperceptive) and semantic levels. All patients had assessments of peripheral hearing and general neuropsychological functions in addition to the experimental auditory battery. While a number of aspects of auditory object analysis were impaired across patient groups and were influenced by general executive (working memory) capacity, certain auditory deficits had some specificity for particular dementia syndromes. Patients with AD had a disproportionate deficit of auditory apperception but preserved timbre processing. Patients with PNFA had salient deficits of timbre and auditory semantic processing, but intact auditory size and apperceptive processing. Patients with LPA had a generalised auditory deficit that was influenced by working memory function. In contrast, the patient with GAA showed substantial preservation of auditory function, but a mild deficit of pitch direction processing and a more severe deficit of auditory apperception. The findings provide evidence for separable stages of auditory object analysis and separable profiles of impaired auditory object cognition in different dementia syndromes. (C) 2011 Elsevier Ltd. All rights reserved

Clustering of smoking, alcohol drinking and cannabis use in adolescents in a rapidly developing country

BACKGROUND: Smoking, alcohol drinking and cannabis use ("risk behaviors") are often initiated at a young age but few epidemiological studies have assessed their joined prevalence in children in developing countries. This study aims at examining the joint prevalence of these behaviors in adolescents in the Seychelles, a rapidly developing country in the Indian Ocean. METHODS: Cross-sectional survey in a representative sample of secondary school students using an anonymous self-administered questionnaire (Global Youth Tobacco Survey). The questionnaire was completed by 1,321 (92%) of 1,442 eligible students aged 11 to 17 years. Main variables of interest included smoking cigarettes on ≥1 day in the past 30 days; drinking any alcohol beverage on ≥1 day in the past 30 days and using cannabis at least once in the past 12 months. RESULTS: In boys and girls, respectively, prevalence (95% CI) was 30% (26–34)/21% (18–25) for smoking, 49% (45–54)/48% (43–52) for drinking, and 17% (15–20)/8% (6–10) for cannabis use. The prevalence of all these behaviors increased with age. Smokers were two times more likely than non-smokers to drink and nine times more likely to use cannabis. Drinkers were three times more likely than non-drinkers to smoke or to use cannabis. Comparison of observed versus expected frequencies of combination categories demonstrated clustering of these risk behaviors in students (P < 0.001). CONCLUSION: Smoking, drinking and cannabis use were common and clustered among adolescents of a rapidly developing country. These findings stress the need for early and integrated prevention programs

Metagenomic Analysis of the Bioremediation of Diesel-Contaminated Canadian High Arctic Soils

As human activity in the Arctic increases, so does the risk of hydrocarbon pollution events. On site bioremediation of contaminated soil is the only feasible clean up solution in these remote areas, but degradation rates vary widely between bioremediation treatments. Most previous studies have focused on the feasibility of on site clean-up and very little attention has been given to the microbial and functional communities involved and their ecology. Here, we ask the question: which microorganisms and functional genes are abundant and active during hydrocarbon degradation at cold temperature? To answer this question, we sequenced the soil metagenome of an ongoing bioremediation project in Alert, Canada through a time course. We also used reverse-transcriptase real-time PCR (RT-qPCR) to quantify the expression of several hydrocarbon-degrading genes. Pseudomonas species appeared as the most abundant organisms in Alert soils right after contamination with diesel and excavation (t = 0) and one month after the start of the bioremediation treatment (t = 1m), when degradation rates were at their highest, but decreased after one year (t = 1y), when residual soil hydrocarbons were almost depleted. This trend was also reflected in hydrocarbon degrading genes, which were mainly affiliated with Gammaproteobacteria at t = 0 and t = 1m and with Alphaproteobacteria and Actinobacteria at t = 1y. RT-qPCR assays confirmed that Pseudomonas and Rhodococcus species actively expressed hydrocarbon degradation genes in Arctic biopile soils. Taken together, these results indicated that biopile treatment leads to major shifts in soil microbial communities, favoring aerobic bacteria that can degrade hydrocarbons

Stochastic Competition between Mechanistically Independent Slippage and Death Pathways Determines Cell Fate during Mitotic Arrest

Variability in cell-to-cell behavior within clonal populations can be attributed to the inherent stochasticity of biochemical reactions. Most single-cell studies have examined variation in behavior due to randomness in gene transcription. Here we investigate the mechanism of cell fate choice and the origin of cell-to-cell variation during mitotic arrest, when transcription is silenced. Prolonged mitotic arrest is commonly observed in cells treated with anti-mitotic drugs. Cell fate during mitotic arrest is determined by two alternative pathways, one promoting cell death, the other promoting cyclin B1 degradation, which leads to mitotic slippage and survival. It has been unclear whether these pathways are mechanistically coupled or independent. In this study we experimentally uncoupled these two pathways using zVAD-fmk to block cell death or Cdc20 knockdown to block slippage. We then used time-lapse imaging to score the kinetics of single cells adopting the remaining fate. We also used kinetic simulation to test whether the behaviors of death versus slippage in cell populations where both pathways are active can be quantitatively recapitulated by a model that assumes stochastic competition between the pathways. Our data are well fit by a model where the two pathways are mechanistically independent, and cell fate is determined by a stochastic kinetic competition between them that results in cell-to-cell variation

Probabilistic (logic) programming concepts

A multitude of different probabilistic programming languages exists today, all extending a traditional programming language with primitives to support modeling of complex, structured probability distributions. Each of these languages employs its own probabilistic primitives, and comes with a particular syntax, semantics and inference procedure. This makes it hard to understand the underlying programming concepts and appreciate the differences between the different languages. To obtain a better understanding of probabilistic programming, we identify a number of core programming concepts underlying the primitives used by various probabilistic languages, discuss the execution mechanisms that they require and use these to position and survey state-of-the-art probabilistic languages and their implementation. While doing so, we focus on probabilistic extensions of logic programming languages such as Prolog, which have been considered for over 20 years

Sampling and counting genome rearrangement scenarios

Even for moderate size inputs, there are a tremendous number of optimal rearrangement scenarios, regardless what the model is and which specific question is to be answered. Therefore giving one optimal solution might be misleading and cannot be used for statistical inferring. Statistically well funded methods are necessary to sample uniformly from the solution space and then a small number of samples are sufficient for statistical inferring

Experimental manipulation of radiographic density in mouse mammary gland

INTRODUCTION: Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density. METHODS: We performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology. RESULTS: Areas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density. CONCLUSION: Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse

Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe

Tuberculosis (TB) was once a major killer in Europe, but it is unclear how the strains and patterns of infection at 'peak TB' relate to what we see today. Here we describe 14 genome sequences of M. tuberculosis, representing 12 distinct genotypes, obtained from human remains from eighteenth-century Hungary using metagenomics. All our historic genotypes belong to M. tuberculosis Lineage 4. Bayesian phylogenetic dating, based on samples with well-documented dates, places the most recent common ancestor of this lineage in the late Roman period. We find that most bodies yielded more than one M. tuberculosis genotype and we document an intimate epidemiological link between infections in two long-dead individuals. Our results suggest that metagenomic approaches usefully inform detection and characterization of historical and contemporary infections

Being Barbie: The Size of One’s Own Body Determines the Perceived Size of the World

A classical question in philosophy and psychology is if the sense of one's body influences how one visually perceives the world. Several theoreticians have suggested that our own body serves as a fundamental reference in visual perception of sizes and distances, although compelling experimental evidence for this hypothesis is lacking. In contrast, modern textbooks typically explain the perception of object size and distance by the combination of information from different visual cues. Here, we describe full body illusions in which subjects experience the ownership of a doll's body (80 cm or 30 cm) and a giant's body (400 cm) and use these as tools to demonstrate that the size of one's sensed own body directly influences the perception of object size and distance. These effects were quantified in ten separate experiments with complementary verbal, questionnaire, manual, walking, and physiological measures. When participants experienced the tiny body as their own, they perceived objects to be larger and farther away, and when they experienced the large-body illusion, they perceived objects to be smaller and nearer. Importantly, despite identical retinal input, this “body size effect” was greater when the participants experienced a sense of ownership of the artificial bodies compared to a control condition in which ownership was disrupted. These findings are fundamentally important as they suggest a causal relationship between the representations of body space and external space. Thus, our own body size affects how we perceive the world