Event-related potentials elicited by spoken relative clauses

Sentence-length event-related potential (ERP) waveforms were obtained from 23 scalp sites as 24 subjects listened to normally spoken sentences of various syntactic structures. The critical materials consisted of 36 sentences each containing one of 2 types of relative clauses that differ in processing difficulty, namely Subject Object (SO) and Subject Subject (SS) relative clauses. Sentence-length ERPs showed several differences in the slow scalp potentials elicited by SO and SS sentences that were similar in their temporal dynamics to those elicited by the same stimuli in a word-by-word reading experiment, although the effects in the two modalities have non identical distributions. Just as for written sentences, there was a large, fronto-central negativity beginning at the linguistically defined "gap" in the SO sentences; this effect was largest for listeners with above-median comprehension rates, and is hypothesized to index changes in on-line processing demands during comprehension

Small Family with Key Contacts: Par14 and Par17 Parvulin Proteins, Relatives of Pin1, Now Emerge in Biomedical Research

The parvulin-type peptidyl-prolyl cis/trans isomerase Pin1 is subject of intense biochemical and clinical research as it seems to be involved in the pathogenesis of certain cancers and protein folding illnesses like Alzheimer’s and Parkinson’s disease. In addition to Pin1, the human genome only contains a single other parvulin locus encoding two protein species—Par14 and Par17. Much less is known about these enzymes although their sequences are highly conserved in all metazoans. Parvulin has been proposed to function as Pin1 complementing enzyme in cell cycle regulation and in chromatin remodelling. Pharmaceutical modulation of Par14 might therefore have benefits for certain types of cancer. Moreover, the Par17 protein that has been shown to be confined to anthropoid primate species only might provide a deeper understanding for human-specific brain development. This review aims at stimulating further research on Par14 and Par17 that are overlooked drug targets in the shadow of an overwhelming plethora of Pin1 literature by summarising all current knowledge on these parvulin proteins

Melting Down Protein Stability: PAPS Synthase 2 in Patients and in a Cellular Environment

Within the crowded and complex environment of the cell, a protein experiences stabilizing excluded-volume effects and destabilizing quinary interactions with other proteins. Which of these prevail, needs to be determined on a case-by-case basis. PAPS synthases are dimeric and bifunctional enzymes, providing activated sulfate in the form of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for sulfation reactions. The human PAPS synthases PAPSS1 and PAPSS2 differ significantly in their protein stability as PAPSS2 is a naturally fragile protein. PAPS synthases bind a series of nucleotide ligands and some of them markedly stabilize these proteins. PAPS synthases are of biomedical relevance as destabilizing point mutations give rise to several pathologies. Genetic defects in PAPSS2 have been linked to bone and cartilage malformations as well as a steroid sulfation defect. All this makes PAPS synthases ideal to study protein unfolding, ligand binding, and the stabilizing and destabilizing factors in their cellular environment. This review provides an overview on current concepts of protein folding and stability and links this with our current understanding of the different disease mechanisms of PAPSS2-related pathologies with perspectives for future research and application

Melting Down Protein Stability: PAPS Synthase 2 in Patients and in a Cellular Environment

Within the crowded and complex environment of the cell, a protein experiences stabilizing excluded-volume effects and destabilizing quinary interactions with other proteins. Which of these prevail, needs to be determined on a case-by-case basis. PAPS synthases are dimeric and bifunctional enzymes, providing activated sulfate in the form of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) for sulfation reactions. The human PAPS synthases PAPSS1 and PAPSS2 differ significantly in their protein stability as PAPSS2 is a naturally fragile protein. PAPS synthases bind a series of nucleotide ligands and some of them markedly stabilize these proteins. PAPS synthases are of biomedical relevance as destabilizing point mutations give rise to several pathologies. Genetic defects in PAPSS2 have been linked to bone and cartilage malformations as well as a steroid sulfation defect. All this makes PAPS synthases ideal to study protein unfolding, ligand binding, and the stabilizing and destabilizing factors in their cellular environment. This review provides an overview on current concepts of protein folding and stability and links this with our current understanding of the different disease mechanisms of PAPSS2-related pathologies with perspectives for future research and application

An Extended Generalized Average Modeling Framework For Power Converters

The Generalized Averaged Modeling (GAM) technique is traditionally employed to capture the dynamic performance of power electronic converters. This paper proposes an improved version of it, named the Extended-GAM (EGAM) technique, which supports the multiplication of two Double Fourier Series (DFS) signals in the time domain. Multiplication of DFS signals in the time domain translates to the 2D-convolution of coefficients of the DFS terms of their equivalent Discrete Fourier Image (DFI) representations. Thus, the proposed EGAM technique, capable of capturing many harmonics present in the output of a power converter, effectively captures the dynamic behavior of power converters excited by two distinct frequencies. The proposed technique is then converted into an algorithm suitable for numerical platforms, which typically use Ordinary Differential Equation (ODE) solvers. The proposed algorithm is validated based on the observations of the effects of harmonic truncation. The efficacy of the proposed technique is assessed through a case study, wherein a single-phase inverter employs LC filters on both the dc-link and the ac-side. Finally, it is shown that the results obtained with the proposed method show an excellent congruence between simulation and hardware experimental models. Additionally, the proposed algorithm is packaged into a MATLAB toolbox and shared for future implementations

Single-Domain Parvulins Constitute a Specific Marker for Recently Proposed Deep-Branching Archaeal Subgroups

Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes assisting protein folding and protein quality control in organisms of all kingdoms of life. In contrast to the other sub-classes of PPIases, the cyclophilins and the FK-506 binding proteins, little was formerly known about the parvulin type of PPIase in Archaea. Recently, the first solution structure of an archaeal parvulin, the PinA protein from Cenarchaeum symbiosum, was reported. Investigation of occurrence and frequency of PPIase sequences in numerous archaeal genomes now revealed a strong tendency for thermophilic microorganisms to reduce the number of PPIases. Single-domain parvulins were mostly found in the genomes of recently proposed deep-branching archaeal subgroups, the Thaumarchaeota and the ARMANs (archaeal Richmond Mine acidophilic nanoorganisms). Hence, we used the parvulin sequence to reclassify available archaeal metagenomic contigs, thereby, adding new members to these subgroups. A combination of genomic background analysis and phylogenetic approaches of parvulin sequences suggested that the assigned sequences belong to at least two distinct groups of Thaumarchaeota. Finally, machine learning approaches were applied to identify amino acid residues that separate archaeal and bacterial parvulin proteins from each other. When mapped onto the recent PinA solution structure, most of these positions form a cluster at one site of the protein possibly indicating a different functionality of the two groups of parvulin proteins

Black hole entropy from an SU(2)-invariant formulation of Type I isolated horizons

A detailed analysis of the spherically symmetric isolated horizon system is performed in terms of the connection formulation of general relativity. The system is shown to admit a manifestly SU(2) invariant formulation where the (effective) horizon degrees of freedom are described by an SU(2) Chern-Simons theory. This leads to a more transparent description of the quantum theory in the context of loop quantum gravity and modifications of the form of the horizon entropy.Comment: 30 pages, 1 figur

The Regulation of Steroid Action by Sulfation and Desulfation

Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined

Structural and functional analysis of the finished genome of the recently isolated toxic Anabaena sp WA102

Background: Very few closed genomes of the cyanobacteria that commonly produce toxic blooms in lakes and reservoirs are available, limiting our understanding of the properties of these organisms. A new anatoxin-a-producing member of the Nostocaceae, Anabaena sp. WA102, was isolated from a freshwater lake in Washington State, USA, in 2013 and maintained in non-axenic culture. Results: The Anabaena sp. WA102 5.7 Mbp genome assembly has been closed with long-read, single-molecule sequencing and separately a draft genome assembly has been produced with short-read sequencing technology. The closed and draft genome assemblies are compared, showing a correlation between long repeats in the genome and the many gaps in the short-read assembly. Anabaena sp. WA102 encodes anatoxin-a biosynthetic genes, as does its close relative Anabaena sp. AL93 (also introduced in this study). These strains are distinguished by differences in the genes for light-harvesting phycobilins, with Anabaena sp. AL93 possessing a phycoerythrocyanin operon. Biologically relevant structural variants in the Anabaena sp. WA102 genome were detected only by long-read sequencing: a tandem triplication of the anaBCD promoter region in the anatoxin-a synthase gene cluster (not triplicated in Anabaena sp. AL93) and a 5-kbp deletion variant present in two-thirds of the population. The genome has a large number of mobile elements (160). Strikingly, there was no synteny with the genome of its nearest fully assembled relative, Anabaena sp. 90. Conclusion: Structural and functional genome analyses indicate that Anabaena sp. WA102 has a flexible genome. Genome closure, which can be readily achieved with long-read sequencing, reveals large scale (e.g., gene order) and local structural features that should be considered in understanding genome evolution and functioKeywords: PacBio, Illumina, Mobilome, Cyanobacteria, Anabaena, Long-read sequencing, Structural variation, Anatoxin-a, Synteny, Tandem repeatKeywords: PacBio, Illumina, Mobilome, Cyanobacteria, Anabaena, Long-read sequencing, Structural variation, Anatoxin-a, Synteny, Tandem repea