Tone Language Fluency Impairs Pitch Discrimination

Here we present evidence that native speakers of a tone language, in which pitch contributes to word meaning, are impaired in the discrimination of falling pitches in tone sequences, as compared to speakers of a non-tone language. Both groups were presented with monotonic and isochronous sequences of five tones (i.e., constant pitch and intertone interval). They were required to detect when the fourth tone was displaced in pitch or time. While speakers of a tone language performed more poorly in the detection of downward pitch changes, they did not differ from non-tone language speakers in their perception of upward pitch changes or in their perception of subtle time changes. Moreover, this impairment cannot be attributed to poor musical abilities since the impairment remains unchanged when individual differences in musical pitch-based processing is taken into account. Thus, the impairment appears highly specific and may reflect the influence of statistical regularities of tone languages

Mathematical modelling of oxygen transport in a muscle-on-chip device

Muscle-on-chip devices aim to recapitulate the physiological characteristics of in vivo muscle tissue and so maintaining levels of oxygen transported to cells is essential for cell survival and for providing the normoxic conditions experienced in vivo. We use finite-element method numerical modelling to describe oxygen transport and reaction in a proposed three-dimensional muscle-on-chip bioreactor with embedded channels for muscle cells and growth medium. We determine the feasibility of ensuring adequate oxygen for muscle cell survival in a device sealed from external oxygen sources and perfused via medium channels. We investigate the effects of varying elements of the bioreactor design on oxygen transport to optimize muscle tissue yield and maintain normoxic conditions. Successful co-culturing of muscle cells with motor neurons can boost muscle tissue function and so we estimate the maximum density of seeded neurons supported by oxygen concentrations within the bioreactor. We show that an enclosed bioreactor can provide sufficient oxygen for muscle cell survival and growth. We define a more efficient arrangement of muscle and perfusion chambers that can sustain a predicted 50% increase in maximum muscle volume per perfusion vessel. A study of simulated bioreactors provides functions for predicting bioreactor designs with normoxic conditions for any size of perfusion vessel, muscle chamber and distance between chambers

Special Issue on Language Disorders and Reading Acquisition : Introductory Remarks

Over the last few years, much attention has been dedicated to exploring the neural and cognitive underpinnings of learning disabilities in reading. Such an interest is partly due to the major socio-economic impact of these disabilities, which are estimated to affect 3-9% of school-age children and adults. The growing body of research in that domain also allows us to improve our understanding of the mechanisms involved in the acquisition of reading in normal children. A conference on this topi..

Prevalence of attention deficit hyperactivity disorder in detention settings: A systematic review and meta-analysis

© 2018 Baggio, Fructuoso, Guimaraes, Fois, Golay, Heller, Perroud, Aubry, Young, Delessert, Gétaz, Tran and Wolff. Background: Previous studies have reported a high prevalence of attention deficit hyperactivity disorder (ADHD) among people living in detention (PLD) corresponding to a five- to ten-fold increase compared to the general population. Our main study objective was to provide an updated ADHD prevalence rate for PLD, including PLD in psychiatric units. Sub-objectives included (i) comparing different ways of assessing ADHD, including DSM-5 criteria and (ii) identifying which types of PLD are more likely to have ADHD. Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines and the MOOSE checklist. PubMed/Medline, PsycINFO, and Web of Sciences were searched combining "ADHD" and "prison" keywords and synonyms for articles published between January 1, 1966 and January 2, 2018. Potential sources of variation to the meta-analytic ADHD prevalence rate were investigated using meta-regressions and subgroups analyses. Results: The meta-analysis pooled 102 original studies including 69,997 participants. The adult ADHD prevalence rate was 26.2% (95% confidence interval: 22.7-29.6). Retrospective assessments of ADHD in childhood were associated with an increased prevalence estimate (41.1, 95% confidence interval: 34.9-47.2, p < 0.001). There was no significant difference in the prevalence estimate between screenings and clinical interviews in adulthood. Only three studies used the DSM-5 definition of ADHD and results were non-significantly different with other DSM versions. We found no difference according to participants' characteristics. Conclusion: Our results confirmed the high prevalence rate of ADHD among PLD, corresponding to a five-fold increase compared to the general population. In light of such high ADHD prevalence, our results reinforce the importance of addressing this critical public health issue by (i) systematically offering ADHD screening and diagnosis to all individuals entering detention, and (ii) delivering treatment, monitoring, and care for ADHD during and after detention. These strategies may help reduce recidivism and reincarceration, as well as violence in detention settings, in addition to improving the health and wellbeing of people living in detention. Additionally, our study suggests that using screening scales may be a reliable way of assessing ADHD, although caution is needed because a complete evaluation by an experienced clinician is required to provide a formal diagnosis

Agro-environmental determinants of avian influenza circulation: A multisite study in Thailand, Vietnam and Madagascar

Outbreaks of highly pathogenic avian influenza have occurred and have been studied in a variety of ecological systems. However, differences in the spatial resolution, geographical extent, units of analysis and risk factors examined in these studies prevent their quantitative comparison. This study aimed to develop a high-resolution, comparative study of a common set of agro-environmental determinants of avian influenza viruses (AIV) in domestic poultry in four different environments: (1) lower-Northern Thailand, where H5N1 circulated in 2004-2005, (2) the Red River Delta in Vietnam, where H5N1 is circulating widely, (3) the Vietnam highlands, where sporadic H5N1 outbreaks have occurred, and (4) the Lake Alaotra region in Madagascar, which features remarkable similarities with Asian agro-ecosystems and where low pathogenic avian influenza viruses have been found. We analyzed H5N1 outbreak data in Thailand in parallel with serological data collected on the H5 subtype in Vietnam and on low pathogenic AIV in Madagascar. Several agro-environmental covariates were examined: poultry densities, landscape dominated by rice cultivation, proximity to a water body or major road, and human population density. Relationships between covariates and AIV circulation were explored using spatial generalized linear models. We found that AIV prevalence was negatively associated with distance to the closest water body in the Red River Delta, Vietnam highlands and Madagascar. We also found a positive association between AIV and duck density in the Vietnam highlands and Thailand, and with rice landscapes in Thailand and Madagascar. Our findings confirm the important role of wetlands-rice-ducks ecosystems in the epidemiology of AI in diverse settings. Variables influencing circulation of the H5 subtype in Southeast Asia played a similar role for low pathogenic AIV in Madagascar, indicating that this area may be at risk if a highly virulent strain is introduced. (Résumé d'auteur

Direct metalation of heteroaromatic esters and nitriles using a mixed lithium-cadmium base. Subsequent conversion to dipyridopyrimidinones.

International audienceAll pyridine nitriles and esters were metalated at the position next to the directing group using (TMP)(3)CdLi in tetrahydrofuran at room temperature. The 2-, 3-, and 4-cyanopyridines were treated with 0.5 equiv of base for 2 h to afford, after subsequent trapping with iodine, the corresponding 3-iodo, 2-iodo, and 3-iodo derivatives, respectively, in yields ranging from 30 to 61%. Cyanopyrazine was similarly functionalized at the 3 position in 43% yield. Ethyl 3-iodopicolinate and -isonicotinate were synthesized from the corresponding pyridine esters in 58 and 65% yield. Less stable ethyl 4-iodonicotinate also formed under the same conditions and was directly converted to ethyl 4-(pyrazol-1-yl)nicotinate in a two-step 38% yield. All three ethyl iodopyridinecarboxylates were involved in a one-pot palladium-catalyzed cross-coupling reaction/cyclization using 2-aminopyridine to afford new dipyrido[1,2-a:3',2'-d]pyrimidin-11-one, dipyrido[1,2-a:4',3'-d]pyrimidin-11-one, and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one in yields ranging from 50 to 62%. A similar cross-coupling/cyclization sequence was applied to methyl 2-chloronicotinate using 2-aminopyridine, 2-amino-5-methylpyridine, and 1-aminoisoquinoline to give the corresponding tricyclic or tetracyclic compounds in 43-79% yield. Dipyrido[1,2-a:4',3'-d]pyrimidin-11-one and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one showed a good bactericidal activity against Pseudomonas aeroginosa . Dipyrido[1,2-a:2',3'-d]pyrimidin-5-one and pyrido[2',3':4,5]pyrimidino[2,1-a]isoquinolin-8-one showed a fungicidal activity against Fusarium and dipyrido[1,2-a:4',3'-d]pyrimidin-11-one against Candida albicans . Ethyl 4-(pyrazol-1-yl)nicotinate and dipyrido[1,2-a:2',3'-d]pyrimidin-5-one have promising cytotoxic activities, the former toward a liver carcinoma cell line (HEPG2) and the latter toward a human breast carcinoma cell line (MCF7

Analysis of the Oxidative Stress Regulon Identifies soxS as a Genetic Target for Resistance Reversal in Multidrug-Resistant Klebsiella pneumoniae

In bacteria, the defense system deployed to counter oxidative stress is orchestrated by three transcriptional factors, SoxS, SoxR, and OxyR. Although the regulon that these factors control is known in many bacteria, similar data are not available for Klebsiella pneumoniae. To address this data gap, oxidative stress was artificially induced in K. pneumoniae MGH78578 using paraquat and the corresponding oxidative stress regulon recorded using transcriptome sequencing (RNA-seq). The soxS gene was significantly induced during oxidative stress, and a knockout mutant was constructed to explore its functionality. The wild type and mutant were grown in the presence of paraquat and subjected to RNA-seq to elucidate the soxS regulon in K. pneumoniae MGH78578. Genes that are commonly regulated both in the oxidative stress and soxS regulons were identified and denoted as the oxidative SoxS regulon; these included a group of genes specifically regulated by SoxS. Efflux pump-encoding genes and global regulators were identified as part of this regulon. Consequently, the isogenic soxS mutant was found to exhibit a reduction in the minimum bactericidal concentration against tetracycline compared to that of the wild type. Impaired efflux activity, allowing tetracycline to be accumulated in the cytoplasm to bactericidal levels, was further evaluated using a tetraphenylphosphonium (TPP+) accumulation assay. The soxS mutant was also susceptible to tetracycline in vivo in a zebrafish embryo model. We conclude that the soxS gene could be considered a genetic target against which an inhibitor could be developed and used in combinatorial therapy to combat infections associated with multidrug-resistant K. pneumoniae. IMPORTANCE Antimicrobial resistance is a global health challenge. Few new antibiotics have been developed for use over the years, and preserving the efficacy of existing compounds is an important step to protect public health. This paper describes a study that examines the effects of exogenously induced oxidative stress on K. pneumoniae and uncovers a target that could be useful to harness as a strategy to mitigate resistance

Peroxiredoxin 6 Fails to Limit Phospholipid Peroxidation in Lung from Cftr-Knockout Mice Subjected to Oxidative Challenge

Oxidative stress plays a prominent role in the pathophysiology of cystic fibrosis (CF). Despite the presence of oxidative stress markers and a decreased antioxidant capacity in CF airway lining fluid, few studies have focused on the oxidant/antioxidant balance in CF cells. The aim of the current study was to investigate the cellular levels of reactive oxygen species (ROS), oxidative damage and enzymatic antioxidant defenses in the lung of Cftr-knockout mice in basal conditions and as a response to oxidative insult

Controlled Sub-Micrometer Hierarchical Textures Engineered in Polymeric Fibers and Microchannels via Thermal Drawing

The controlled texturing of surfaces at the micro- and nanoscales is a powerful method for tailoring how materials interact with liquids, electromagnetic waves, or biological tissues. The increasing scientific and technological interest in advanced fibers and fabrics has triggered a strong motivation for leveraging the use of textures on fiber surfaces. Thus far however, fiber-processing techniques have exhibited an inherent limitation due to the smoothing out of surface textures by polymer reflow, restricting achievable feature sizes. In this article, a theoretical framework is established from which a strategy is developed to reduce the surface tension of the textured polymer, thus drastically slowing down thermal reflow. With this approach the fabrication of potentially kilometers-long polymer fibers with controlled hierarchical surface textures of unprecedented complexity and with feature sizes down to a few hundreds of nanometers is demonstrated, two orders of magnitude below current configurations. Using such fibers as molds, 3D microchannels are also fabricated with textured inner surfaces within soft polymers such as poly(dimethylsiloxane), at dimensions and a degree of simplicity impossible to reach with current techniques. This strategy for the texturing of high curvature surfaces opens novel opportunities in bioengineering, regenerative scaffolds, microfluidics, and smart textiles