Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia.

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468).

Stabilization of the Nickel Binding Loop in NiSOD and Related Model Complexes: Thermodynamic and Structural Features.

Detailed equilibrium and spectroscopic characterization of the complex formation processes of the nickel binding loop in NiSOD and its related fragments is reported in the slightly acidic-alkaline pH range. The N-terminally free and protected nonapeptides HCDLPCGVY-NH (NiSODM), HCDLACGVY-NH (NiSODM), and Ac-HCDLPCGVY-NH (NiSODM) and the N-terminally shortened analogues HCDL-NH and HCA-NH were synthesized, and their nickel(II) complexes were studied by potentiometric and several spectroscopic techniques. EPR spectroscopy was also used to assign the coordinating donor sites after the in situ oxidation of nickel(II) complexes.

New Water-Soluble Copper(II) Complexes with Morpholine-Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action.

Six morpholine-(iso)thiosemicarbazone hybrids HL-HL and their Cu(II) complexes with good-to-moderate solubility and stability in water were synthesized and characterized. Cu(II) complexes [Cu(L)Cl] (1-6) formed weak dimeric associates in the solid state, which did not remain intact in solution as evidenced by ESI-MS. The lead proligands and Cu(II) complexes displayed higher antiproliferative activity in cancer cells than triapine.

Size-Exclusion Borane-Catalyzed Domino 1,3-Allylic/Reductive Ireland-Claisen Rearrangements: Impact of the Electronic and Structural Parameters on the 1,3-Allylic Shift Aptitude.

The reductive Ireland-Claisen rearrangement through borane-mediated hydrosilylation is reported. The method employs a borane catalyst with a special structural design and affords access to synthetically relevant products with high diastereoselectivity. Depending on electronic and structural parameters, the reaction can be coupled with a 1,3-allylic shift, thus the valence isomer of the Ireland-Claisen product is formed.

Similar but separate systems underlie perceptual bistability in vision and audition.

The dynamics of perceptual bistability, the phenomenon in which perception switches between different interpretations of an unchanging stimulus, are characterised by very similar properties across a wide range of qualitatively different paradigms. This suggests that perceptual switching may be triggered by some common source. However, it is also possible that perceptual switching may arise from a distributed system, whose components vary according to the specifics of the perceptual experiences involved.

The Goldilocks Principle in Phase Labeling. Minimalist and Orthogonal Phase Tagging for Chromatography-Free Mitsunobu Reaction.

An inexpensive and chromatography-free Mitsunobu methodology has been developed using low molecular weight and orthogonally phase-tagged reagents, a tert-butyl-tagged highly apolar phosphine, and a water-soluble DIAD analogue. The byproduct of the Mitsunobu reactions can be removed by sequential liquid-liquid extractions using traditional solvents such as hexanes, MeOH, water, and EtOAc. Owing to the orthogonal phase labeling, the spent reagents can be regenerated.

Visual mismatch negativity (vMMN) for low- and high-level deviances: A control study.

The aim of our studies was to separate the effects of violating a sequential rule (genuine visual mismatch negativity; gvMMN) from the decreased activity in response to repeated stimuli (stimulus-specific adaptation; SSA) for simple and more complex stimuli. To accomplish this goal, different control procedures were applied with the aim of finding the correct control for vMMN studies. Event-related brain electric activity (ERPs) was measured in response to nonattended visual stimuli that were presented either in an oddball manner or in various control sequences.

Signalling assemblies: the odds of symmetry.

The assembly of proteins into complexes is fundamental to nearly all biological signalling processes. Symmetry is a dominant feature of the structures of experimentally determined protein complexes, observed in the vast majority of homomers and many heteromers. However, some asymmetric structures exist, and asymmetry also often forms transiently, intractable to traditional structure determination methods.

Synthesis and Enantiomeric Recognition Studies of Optically Active Pyridino-Crown Ethers Containing an Anthracene Fluorophore Unit.

Novel enantiopure pyridino-18-crown-6 ether-based sensor molecules containing an anthracene fluorophore unit were synthesized. Their enantiomeric recognition abilities toward the enantiomers of 1-phenylethylamine hydrogen perchlorate (PhEt), 1-(1-naphthyl)ethylamine hydrogen perchlorate (NapEt), phenylglycine methyl ester hydrogen perchlorate (PhgOMe), and phenylalanine methyl ester hydrogen perchlorate (PheOMe) were examined in acetonitrile using fluorescence spectroscopy. The sensor molecules showed appreciable enantiomeric recognition toward the enantiomers of NapEt, PhEt, and PhgOMe.

Age-dependent characteristics of feedback evaluation related to monetary gains and losses.

Monitoring the consequences of actions is of crucial importance in order to optimize behavior to the challenges of the environment. Recently the age-related aspects of this fundamentally important cognitive processing have been brought into the focus of investigation since behavioral monitoring and related control mechanisms are widely known to be affected by aging. Processing of feedback stimuli is a core mechanism for rapid evaluation of the functionally significant aspects of outcome, guiding behavior towards avoidance or approach.

Antioxidant value and element content in some tinctures used in medication.

Tinctures are almost the oldest medicines and their use is substantial in the medication nowadays as well. The antioxidant values by ferric reducing/antioxidant power (FRAP) method and element content by inductively coupled plasma optical emission spectrometry (ICP-OES) were investigated in some tinctures official in the VII. and VIII.

A fluid response: Alpha-amylase reactions to acute laboratory stress are related to sample timing and saliva flow rate.

Salivary alpha-amylase (sAA) is used as a sympathetic (SNS) stress marker, though its release is likely co-determined by SNS and parasympathetic (PNS) activation. The SNS and PNS show asynchronous changes during acute stressors, and sAA responses may thus vary with sample timing. Thirty-four participants underwent an eight-minute memory task (MT) and cold pressor task (CPT).

Decreased functional activity of multidrug resistance protein in primary colorectal cancer.

Background: The ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies.

A mechanistic view of lipid membrane disrupting effect of PAMAM dendrimers.

The effect of 5th generation polyamidoamine (PAMAM G5) dendrimers on multilamellar dipalmitoylphosphocholine (DPPC) vesicles was investigated. PAMAM was added in two different concentrations to the lipids (10(-3) and 10(-2) dendrimer/lipid molar ratios). The thermal behavior of the evolved systems was characterized by DSC; while the structure and the morphology were investigated with small- and wide-angel X-ray scattering (SWAXS), freeze-fracture electron microscopy (FFTEM) and phosphorus-31 nuclear magnetic resonance ((31)P NMR) spectroscopy, respectively.

Influence of poly(ethylene oxide)-based copolymer on protein adsorption and bacterial adhesion on stainless steel: modulation by surface hydrophobicity.

The aim of the present work is to study the adhesion of Pseudomonas NCIMB 2021, a typical aerobic marine microorganism, on stainless steel (SS) substrate. More particularly, the potential effect on adhesion of adsorbed poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer is investigated. Bacterial attachment experiments were carried out using a modified parallel plate flow chamber, allowing different surface treatments to be compared in a single experiment.

Asymmetric perturbations of signalling oligomers.

This review focuses on rapid and reversible noncovalent interactions for symmetric oligomers of signalling proteins. Symmetry mismatch, transient symmetry breaking and asymmetric perturbations via chemical (ligand binding) and physical (electric or mechanic) effects can initiate the signalling events. Advanced biophysical methods can reveal not only structural symmetries of stable membrane-bound signalling proteins but also asymmetric functional transition states.

Comparison of complexes formed by a crustacean and a vertebrate trypsin with bovine pancreatic trypsin inhibitor - the key to achieving extreme stability?

This paper provides evidence for the extremely high resistance of a complex of crayfish trypsin (CFT) and bovine pancreatic trypsin inhibitor (BPTI) against heating and chemical denaturing agents such as sodium dodecyl sulfate (SDS) and urea. To dissociate this complex, 15 min boiling in SDS was necessary, compared to a complex of bovine trypsin (BT) (EC 3.4.

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications.

Saliency or template? ERP evidence for long-term representation of word stress.

The present study investigated the event-related brain potential (ERP) correlates of word stress processing. Previous results showed that the violation of a legal stress pattern elicited two consecutive Mismatch Negativity (MMN) components synchronized to the changes on the first and second syllable. The aim of the present study was to test whether ERPs reflect only the detection of salient features present on the syllables, or they reflect the activation of long-term stress related representations.