Chromatin regulators, phenotypic robustness, and autism risk.

Though extensively characterized clinically, the causes of autism spectrum disorder (ASD) remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD.

Emerging bioinformatics approaches for analysis of NGS-derived coding and non-coding RNAs in neurodegenerative diseases.

Neurodegenerative diseases in general and specifically late-onset Alzheimer's disease (LOAD) involve a genetically complex and largely obscure ensemble of causative and risk factors accompanied by complex feedback responses. The advent of "high-throughput" transcriptome investigation technologies such as microarray and deep sequencing is increasingly being combined with sophisticated statistical and bioinformatics analysis methods complemented by knowledge-based approaches such as Bayesian Networks or network and graph analyses. Together, such "integrative" studies are beginning to identify co-regulated gene networks linked with biological pathways and potentially modulating disease predisposition, outcome, and progression.

Labile iron in cells and body fluids: physiology, pathology, and pharmacology.

In living systems iron appears predominantly associated with proteins, but can also be detected in forms referred as labile iron, which denotes the combined redox properties of iron and its amenability to exchange between ligands, including chelators. The labile cell iron (LCI) composition varies with metal concentration and substances with chelating groups but also with pH and the medium redox potential. Although physiologically in the lower μM range, LCI plays a key role in cell iron economy as cross-roads of metabolic pathways.

Group II intron splicing factors in plant mitochondria.

Group II introns are large catalytic RNAs (ribozymes) which are found in bacteria and organellar genomes of several lower eukaryotes, but are particularly prevalent within the mitochondrial genomes (mtDNA) in plants, where they reside in numerous critical genes. Their excision is therefore essential for mitochondria biogenesis and respiratory functions, and is facilitated in vivo by various protein cofactors. Typical group II introns are classified as mobile genetic elements, consisting of the self-splicing ribozyme and its intron-encoded maturase protein.

Improved control of exogenous attention in action video game players.

Action video game players (VGPs) have demonstrated a number of attentional advantages over non-players. Here, we propose that many of those benefits might be underpinned by improved control over exogenous (i.e.

Rescue of tau-induced synaptic transmission pathology by paclitaxel.

Behavioral and electrophysiological studies of Alzheimer's disease (AD) and other tauopathies have revealed that the onset of cognitive decline correlates better with synaptic dysfunctions than with hallmark pathologies such as extracellular amyloid-β plaques, intracellular hyperphosphorylated tau or neuronal loss. Recent experiments have also demonstrated that anti-cancer microtubule (MT)-stabilizing drugs can rescue tau-induced behavioral decline and hallmark neuron pathologies. Nevertheless, the mechanisms underlying tau-induced synaptic dysfunction as well as those involved in the rescue of cognitive decline by MTs-stabilizing drugs remain unclear.

Predicted overlapping microRNA regulators of acetylcholine packaging and degradation in neuroinflammation-related disorders.

MicroRNAs (miRNAs) can notably control many targets each and regulate entire cellular pathways, but whether miRNAs can regulate complete neurotransmission processes is largely unknown. Here, we report that miRNAs with complementary sequence motifs to the key genes involved in acetylcholine (ACh) synthesis and/or packaging show massive overlap with those regulating ACh degradation. To address this topic, we first searched for miRNAs that could target the 3'-untranslated regions of the choline acetyltransferase (ChAT) gene that controls ACh synthesis; the vesicular ACh transporter (VAChT), encoded from an intron in the ChAT gene and the ACh hydrolyzing genes acetyl- and/or butyrylcholinesterase (AChE, BChE).

Protein folding as a driving force for dual protein targeting in eukaryotes.

It is well documented that in eukaryotic cells molecules of one protein can be located in several subcellular locations, a phenomenon termed dual targeting, dual localization, or dual distribution. The differently localized identical or nearly identical proteins are termed "echoforms." Our conventional definition of dual targeted proteins refers to situations in which one of the echoforms is translocated through/into a membrane.

Differential diagnosis of sensory modulation disorder (SMD) and attention deficit hyperactivity disorder (ADHD): participation, sensation, and attention.

Differential diagnosis between sensory modulation disorder (SMD) and attention deficit hyperactivity disorder (ADHD) is often challenging, since these disorders occur at a high rate of co-morbidity and share several clinical characteristics. Preliminary studies providing evidence that these are distinct disorders have focused solely on body functions, using sophisticated laboratory measurements. Moreover, no studies have compared participation profiles of these populations.

Can consumers make affordable care affordable? The value of choice architecture.

Tens of millions of people are currently choosing health coverage on a state or federal health insurance exchange as part of the Patient Protection and Affordable Care Act. We examine how well people make these choices, how well they think they do, and what can be done to improve these choices. We conducted 6 experiments asking people to choose the most cost-effective policy using websites modeled on current exchanges.

Genome-wide assessment of post-transcriptional control in the fly brain.

Post-transcriptional control of gene expression has central importance during development and adulthood and in physiology in general. However, little is known about the extent of post-transcriptional control of gene expression in the brain. Most post-transcriptional regulatory effectors (e.

Life at high salt concentrations, intracellular KCl concentrations, and acidic proteomes.

Extremely halophilic microorganisms that accumulate KCl for osmotic balance (the Halobacteriaceae, Salinibacter) have a large excess of acidic amino acids in their proteins. This minireview explores the occurrence of acidic proteomes in halophiles of different physiology and phylogenetic affiliation. For fermentative bacteria of the order Halanaerobiales, known to accumulate KCl, an acidic proteome was predicted.

Effects of arginine vasopressin on musical working memory.

Previous genetic studies showed an association between variations in the gene coding for the 1a receptor of the neuro-hormone arginine vasopressin (AVP) and musical working memory (WM). The current study set out to test the influence of intranasal administration (INA) of AVP on musical as compared to verbal WM using a double blind crossover (AVP-placebo) design. Two groups of 25 males were exposed to 20 IU of AVP in one session, and 20 IU of saline water (placebo) in a second session, 1 week apart.

Release properties of individual presynaptic boutons expressed during homosynaptic depression and heterosynaptic facilitation of the Aplysia sensorimotor synapse.

Much of what we know about the mechanisms underlying Homosynaptic Depression (HSD) and heterosynaptic facilitation is based on intracellular recordings of integrated postsynaptic potentials (PSPs). This methodological approach views the presynaptic apparatus as a single compartment rather than taking a more realistic representation reflecting the fact that it is made up of tens to hundreds of individual and independent Presynaptic Release Boutons (PRBs). Using cultured Aplysia sensorimotor synapses, we reexamined HSD and its dishabituation by imaging the release properties of individual PRBs.

Compositionality in neural control: an interdisciplinary study of scribbling movements in primates.

This article discusses the compositional structure of hand movements by analyzing and modeling neural and behavioral data obtained from experiments where a monkey (Macaca fascicularis) performed scribbling movements induced by a search task. Using geometrically based approaches to movement segmentation, it is shown that the hand trajectories are composed of elementary segments that are primarily parabolic in shape. The segments could be categorized into a small number of classes on the basis of decreasing intra-class variance over the course of training.

A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis.

Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a neurodegenerative disorder with a poorly understood molecular mechanism. It is caused by mutations in Pantothenate Kinase, the first enzyme in the Coenzyme A (CoA) biosynthetic pathway. Here, we developed a Drosophila model of PKAN (tim-fbl flies) that allows us to continuously monitor the modeled disease in the brain.

Dissociating between object affordances and spatial compatibility effects using early response components.

objects may be perceived not only in terms of visual features, but also in terms of possibilities for action. Previous studies showed that when a centrally located object has a salient graspable feature (e.g.

Is there any electrophysiological evidence for subliminal error processing?

The role of error awareness in executive control and modification of behavior is not fully understood. In line with many recent studies showing that conscious awareness is unnecessary for numerous high-level processes such as strategic adjustments and decision making, it was suggested that error detection can also take place unconsciously. The Error Negativity (Ne) component, long established as a robust error-related component that differentiates between correct responses and errors, was a fine candidate to test this notion: if an Ne is elicited also by errors which are not consciously detected, it would imply a subliminal process involved in error monitoring that does not necessarily lead to conscious awareness of the error.

Characterization of fluoroquinolone resistance and qnr diversity in Enterobacteriaceae from municipal biosolids.

Municipal biosolids produced during activated sludge treatment applied in wastewater treatment plants, are significant reservoirs of antibiotic resistance, since they assemble both natural and fecal microbiota, as well as residual concentrations of antibiotic compounds. This raises major concerns regarding the environmental and epidemiological consequences of using them as fertilizers for crops. The second generation fluoroquinolone ciprofloxacin is probably the most abundant antibiotic compound detected in municipal biosolids due to its widespread use and sorption properties.

Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes.

MicroRNAs (miRNAs) are key post transcriptional regulators of their multiple target genes. However, the detailed profile of miRNA expression in Parkinson's disease, the second most common neurodegenerative disease worldwide and the first motor disorder has not been charted yet. Here, we report comprehensive miRNA profiling by next-generation small-RNA sequencing, combined with targets inspection by splice-junction and exon arrays interrogating leukocyte RNA in Parkinson's disease patients before and after deep brain stimulation (DBS) treatment and of matched healthy control volunteers (HC).

Detecting concealed information from groups using a dynamic questioning approach: simultaneous skin conductance measurement and immediate feedback.

Lie detection procedures typically aim at determining the guilt or innocence of a single suspect. The Concealed Information Test (CIT), for example, has been shown to be highly successful in detecting the presence or absence of crime-related information in a suspect's memory. Many of today's security threats, however, do not come from individuals, but from organized groups such as criminal organizations or terrorist networks.

Development of targeted therapy for a broad spectrum of solid tumors mediated by a double promoter plasmid expressing diphtheria toxin under the control of IGF2-P4 and IGF2-P3 regulatory sequences.

Background: The human IGF2-P4 and IGF2-P3 promoters are highly active in a variety of human cancers, while existing at a nearly undetectable level in the surrounding normal tissue. Thus, a double promoter DTA-expressing vector was created, carrying on a single construct two separate genes expressing the diphtheria toxin a-fragment (DTA), from two different regulatory sequences, selected from the cancer-specific promoters IGF2-P4 and IGF2-P3.

Methods: The therapeutic potential of the double promoter toxin vector P4-DTA-P3-DTA was tested in different cancer cells (pancreatic cancer, ovarian cancer and HCC).

Current research and potential applications of the concealed information test: an overview.

Research interest in psychophysiological detection of deception has significantly increased since the September 11 terror attack in the USA. In particular, the concealed information test (CIT), designed to detect memory traces that can connect suspects to a certain crime, has been extensively studied. In this paper I will briefly review several psychophysiological detection paradigms that have been studied, with a focus on the CIT.

Toward on-chip, in-cell recordings from cultured cardiomyocytes by arrays of gold mushroom-shaped microelectrodes.

Cardiological research greatly rely on the use of cultured primary cardiomyocytes (CMs). The prime methodology to assess CM network electrophysiology is based on the use of extracellular recordings by substrate-integrated planar Micro-Electrode Arrays (MEAs). Whereas this methodology permits simultaneous, long-term monitoring of the CM electrical activity, it limits the information to extracellular field potentials (FPs).