546 research outputs found
A destressing "deafness" in French?
French is a language in which accent is mandatory on the last syllable of every content word. In contrast, Spanish uses accent to distinguish different lexical items (e.g., b'ebe vs beb'e). Two population of subjects were tested on the same materials to study whether such linguistic differences have an impact on the perceptual capacities of listeners. In Experiment 1, using an ABX paradigm, we find that French Subjects have a surprising deficit compared to Spanish Subjects in making accent distinctions. In Experiment 2, we find that Spanish subjects cannot ignore irrelevant differences in accent in a phoneme-based ABX task, whereas French Subjects have no difficulty at all. In Experiment 3, we replicate the basic French finding, and find that Spanish subjects benefit from redundant accent information even when phonemic information alone is sufficient to perform the task. In our final Experiment 4, we show that French subjects can hear the acoustic correlates of accent; their problem seem to arise at the level of short term memory. Implications for language-specific processing and acquisition are discussed
Connections between Classical and Parametric Network Entropies
This paper explores relationships between classical and parametric measures of graph (or network) complexity. Classical measures are based on vertex decompositions induced by equivalence relations. Parametric measures, on the other hand, are constructed by using information functions to assign probabilities to the vertices. The inequalities established in this paper relating classical and parametric measures lay a foundation for systematic classification of entropy-based measures of graph complexity
Aptamer-based multiplexed proteomic technology for biomarker discovery
Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine
Structural Intermediates in a Model of the Substrate Translocation Path of the Bacterial Glutamate Transporter Homologue GltPh
Conservation of freshwater bivalves at the global scale: diversity, threats and research needs
Bivalves are ubiquitous members of freshwater ecosystems and responsible for important functions and services. The present paper revises freshwater bivalve diversity, conservation status and threats at the global scale and discusses future research needs and management actions. The diversity patterns are uneven across the globe with hotspots in the interior basin in the United States of America (USA), Central America, Indian subcontinent and Southeast Asia. Freshwater bivalves are affected by multiple threats that vary across the globe; however, pollution and natural system (habitat) modifications being consistently found as the most impacting. Freshwater bivalves are among the most threatened groups in the world with 40% of the species being near threatened, threatened or extinct, and among them the order Unionida is the most endangered. We suggest that global cooperation between scientists, managers, politicians and general public, and application of new technologies (new generation sequencing and remote sensing, among others) will strengthen the quality of studies on the natural history and conservation of freshwater bivalves. Finally, we introduce the articles published in this special issue of Hydrobiologia under the scope of the Second International Meeting on Biology and Conservation of Freshwater Bivalves held in 2015 in Buffalo, New York, USA.This work was supported by FCT—Foundation for Science and
Technology, Project 3599—Promote the Scientific Production
and Technological Development and Thematic 3599-PPCDT by
FEDER as part of the project FRESHCO: multiple implications
of invasive species on Freshwater Mussel co-extinction
processes (Contract: PTDC/AGRFOR/1627/2014). FCT also
supported MLL under Grant (SFRH/BD/115728/2016)
Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes
Lis1-Nde1 integrates cerebral cortical neurogenesis with neuronal migration by stabilizing the basal-lateral surface of radial glial cells
ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing
A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research
A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome
Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1–2%) of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different classes of noncoding RNAs and their relevance to human disease. Using genomic approaches we discovered FMR4, a primate-specific noncoding RNA transcript (2.4 kb) that resides upstream and likely shares a bidirectional promoter with FMR1. FMR4 is a product of RNA polymerase II and has a similar half-life to FMR1. The CGG expansion in the 5′ UTR of FMR1 appears to affect transcription in both directions as we found FMR4, similar to FMR1, to be silenced in fragile X patients and up-regulated in premutation carriers. Knockdown of FMR4 by several siRNAs did not affect FMR1 expression, nor vice versa, suggesting that FMR4 is not a direct regulatory transcript for FMR1. However, FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. Collectively, our results demonstrate an antiapoptotic function of FMR4 and provide evidence that a well-studied genomic locus can show unexpected functional complexity. It cannot be excluded that altered FMR4 expression might contribute to aspects of the clinical presentation of fragile X syndrome and/or related disorders
Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects
Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation
<p>Abstract</p> <p>Background and aims</p> <p>There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones.</p> <p>Methods</p> <p>3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I).</p> <p>Results</p> <p>The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m<sup>2</sup>, resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (χ<sup>2 </sup>= 5.62/χ<sup>2 </sup>= 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5<sup>th </sup>percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters.</p> <p>Conclusions</p> <p>Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.</p
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