bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of thyroid hormone receptor binding sites in developing mouse cerebellum
Authors: Gagne Remi , Green James R , Dong Hongyan , Wade Mike G , Yauk Carole L 
Published: May 2013

Abstract

Background
Thyroid hormones play an essential role in early vertebrate development as well as other key processes. One of its modes of action is to bind to the thyroid hormone receptor (TR) which, in turn, binds to thyroid response elements (TREs) in promoter regions of target genes. The sequence motif for TREs remains largely undefined as does the precise chromosomal location of the TR binding sites. A chromatin immunoprecipitation on microarray (ChIP-chip) experiment was conducted using mouse cerebellum post natal day (PND) 4 and PND15 for the thyroid hormone receptor (TR) beta 1 to map its binding sites on over 5000 gene promoter regions. We have performed a detailed computational analysis of these data.

Results
By analysing a recent spike-in study, the optimal normalization and peak identification approaches were determined for our dataset. Application of these techniques led to the identification of 211 ChIP-chip peaks enriched for TR binding in cerebellum samples. ChIP-PCR validation of 25 peaks led to the identification of 16 true positive TREs. Following a detailed literature review to identify all known mouse TREs, a position weight matrix (PWM) was created representing the classic TRE sequence motif. Various classes of promoter regions were investigated for the presence of this PWM, including permuted sequences, randomly selected promoter sequences, and genes known to be regulated by TH. We found that while the occurrence of the TRE motif is strongly correlated with gene regulation by TH for some genes, other TH-regulated genes do not exhibit an increased density of TRE half-site motifs. Furthermore, we demonstrate that an increase in the rate of occurrence of the half-site motifs does not always indicate the specific location of the TRE within the promoter region. To account for the fact that TR often operates as a dimer, we introduce a novel dual-threshold PWM scanning approach for identifying TREs with a true positive rate of 0.73 and a false positive rate of 0.2. Application of this approach to ChIP-chip peak regions revealed the presence of 85 putative TREs suitable for further in vitro validation.

Conclusions
This study further elucidates TRβ gene regulation in mouse cerebellum, with 211 promoter regions identified to bind to TR. While we have identified 85 putative TREs within these regions, future work will study other mechanisms of action that may mediate the remaining observed TR-binding activity.
Virophages, polintons, and transpovirons: a complex evolutionary network of diverse selfish genetic elements with different reproduction strategies
Authors: Yutin Natalya , Raoult Didier , Koonin Eugene V 
Published: May 2013

Abstract

Background
Recent advances of genomics and metagenomics reveal remarkable diversity of viruses and other selfish genetic elements. In particular, giant viruses have been shown to possess their own mobilomes that include virophages, small viruses that parasitize on giant viruses of the Mimiviridae family, and transpovirons, distinct linear plasmids. One of the virophages known as the Mavirus, a parasite of the giant Cafeteria roenbergensis virus, shares several genes with large eukaryotic self-replicating transposon of the Polinton (Maverick) family, and it has been proposed that the polintons evolved from a Mavirus-like ancestor.

Results
We performed a comprehensive phylogenomic analysis of the available genomes of virophages and traced the evolutionary connections between the virophages and other selfish genetic elements. The comparison of the gene composition and genome organization of the virophages reveals 6 conserved, core genes that are organized in partially conserved arrays. Phylogenetic analysis of those core virophage genes, for which a sufficient diversity of homologs outside the virophages was detected, including the maturation protease and the packaging ATPase, supports the monophyly of the virophages. The results of this analysis appear incompatible with the origin of polintons from a Mavirus-like agent but rather suggest that Mavirus evolved through recombination between a polinton and an unknownvirus. Altogether, virophages, polintons, a distinct Tetrahymena transposable element Tlr1, transpovirons, adenoviruses, and some bacteriophages form a network of evolutionary relationships that is held together by overlapping sets of shared genes and appears to represent a distinct module in the vast total network of viruses and mobile elements.

Conclusions
The results of the phylogenomic analysis of the virophages and related genetic elements are compatible with the concept of network-like evolution of the virus world and emphasize multiple evolutionary connections between bona fide viruses and other classes of capsid-less mobile elements.
A multi-site single blind clinical study to compare the effects of prolonged exposure, eye movement desensitization and reprocessing and waiting list on patients with a current diagnosis of psychosis and co morbid post traumatic stress disorder: study protocol for the randomized controlled trial Treating Trauma in Psychosis
Authors: de Bont Paul AJM , van den Berg David PG , van der Vleugel Berber M , de Roos Carlijn , Mulder Cornelis L , Becker Eni S , de Jongh Ad , van der Gaag Mark , van Minnen Agnes 
Published: May 2013

Abstract

Background
Trauma contributes to psychosis and in psychotic disorders post-traumatic stress disorder (PTSD) is often a comorbid disorder. A problem is that PTSD is underdiagnosed and undertreated in people with psychotic disorders. This study’s primary goal is to examine the efficacy and safety of prolonged exposure and eye movement desensitization and reprocessing (EMDR) for PTSD in patients with both psychotic disorders and PTSD, as compared to a waiting list. Secondly, the effects of both treatments are determined on (a) symptoms of psychosis, in particular verbal hallucinations, (b) depression and social performance, and (c) economic costs. Thirdly, goals concern links between trauma exposure and psychotic symptomatology and the prevalence of exposure to traumatic events, and of PTSD. Fourthly predictors, moderators, and mediators for treatment success will be explored. These include cognitions and experiences concerning treatment harm, credibility and burden in both participants and therapists.

Methods/Design
A short PTSD-screener assesses the possible presence of PTSD in adult patients (21- to 65- years old) with psychotic disorders, while the Clinician Administered PTSD Scale interview will be used for the diagnosis of current PTSD. The M.I.N.I. Plus interview will be used for diagnosing lifetime psychotic disorders and mood disorders with psychotic features. The purpose is to include consenting participants (N = 240) in a multi-site single blind randomized clinical trial. Patients will be allocated to one of three treatment conditions (N = 80 each): prolonged exposure or EMDR (both consisting of eight weekly sessions of 90 minutes each) or a six-month waiting list. All participants are subjected to blind assessments at pre-treatment, twomonths post treatment, and six monthspost treatment. In addition, participants in the experimental conditions will have assessments at mid treatment and at 12 months follow-up.

Discussion
The results from the post treatment measurement can be considered strong empirical indicators of the safety and effectiveness of prolonged exposure and EMDR. The six-month and twelve-month follow-up data have the potential of reliably providing documentation of the long-term effects of both treatments on the various outcome variables. Data from pre-treatment and midtreatment can be used to reveal possible pathways of change.

Trial registration
Trial registration:ISRCTN79584912
Photocatalytic effect of TiO2and the effect of dopants on degradation of brilliant green
Authors: Munusamy Shamalah , Aparna Rangabhatla sai laxmi , Prasad Rangabhatla gunneswara subramanya v 
Published: May 2013

Abstract
Photocatalysis speeds up the photoreaction in the presence of a catalyst. TiO2 has low toxicity, less resistance and less corrosion and has semiconductor properties. Its strong oxidative potential of the positive holes oxidizes water to create hydroxyl radicals. Moreover, TiO2 has been proven to be a tremendous photocatalyst compound by which many organic substrates have been shown to be oxidatively degraded under UV irradiation. In this research the photocatalytic effect of TiO2 on degradation of Brilliant Green (BG) was studied. In conjunction the effect of dopants such as Zn and Cu on photocatalysis of TiO2 were also studied. Structural and morphological properties of TiO2 were characterized by SEM and XRD. From this research the initial concentration of sample, pH of samples, chemical structure of dyes and catalyst loading were most valuable parameters for dye degradation. TiO2 showed excellent result on degradation of BG compared with doped TiO2. 99% degradation was obtained in presence of TiO2, followed by TiO2/Zn for 87% and TiO2/Cu for 46%. TiO2 doped with transition metals can increase or decrease photocatalytic degradation of dyes.
Recovery of DNA Synthesis from Inhibition by Ultraviolet Light in Mammalian Cells
Authors: Ventura Armando M. , Ortega J. Miguel , Schumacher R. Ivan , Meneghini Rogerio 
Published: May 2013

ABSTRACT
In general mammalian cells recover from DNA synthesis inhibition by ultraviolet light (u.v.) before most of the pyrimidine dimers have been removed from the genome. This is a complex phenomenon whose biological significance has not been fully assessed. In Chinese hamster V79 cells this recovery seems to be directly coupled to an enhanced rate of double-stranded DNA elongation. The presence of the DNA polymerase it inhibitor, aphidicolin, after u.v. irradiation produces two different responses. At low concentration, sufficient to inhibit 95 % of DNA replication but having no effect on excision repair, the drug has no effect on the recovery. This shows that ongoing replicative DNA synthesis is not required for recovery. At higher concentrations of aphidicolin, sufficient to block excision repair, the recovery phenomenon was prevented. The recovery was also prevented by actinomycin D at a concentration that inhibits 60 % of RNA synthesis. In quantitative autoradiography experiments in which previously irradiated cells were fused with unirradiated cells the nuclei of the latter exhibited a higher resistance to inhibition by u.v. than nuclei from non-fused cells. These results indicate that: (1) even the low repair rate exhibited by V79 cells (relative to human cells) is important for recovery; although most of the dimers remain in the V79 genome after recovery of DNA synthesis, either the removal of lesions from some important region of chromatin or the activity of the repair process itself is important for the recovery; (2) the recovery mechanism is induced and depends on RNA synthesis and the production of specific factors.
Finally, we have observed that cells previously treated with fluorodeoxyuridine become more resistant to inhibition by u.v. After irradiation these cells replicate DNA faster than untreated cells. Since it has been shown that this drug activates unused origins of replication in Chinese hamster cells, reducing the average replicon size, we assume that the acquired resistance has to do with the operation of a larger number of smaller replicons. This may also be the mechanism whereby recovery from inhibition occurs after u.v. irradiation.
The Role of O6-Methylguanine in Human Cell Killing, Sister Chromatid Exchange Induction and Mutagenesis: A Review
Authors: Day Rufus S. , Babich Michael A. , Yarosh Daniel B. , Scudiero Dominic A. 
Published: May 2013

ABSTRACT
O 1-methylguanine (O1mG) produced in DNA by such SN1 methylating agents as N-methyl-N-nitrososurea and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) has been suggested by some to be the lesion that leads to certain biological endpoints in mammalian cells: cell killing, sister chromatid exchange (SCE) production, mutagenesis and cellular transformation. Other evidence is interpreted as inconsistent with this point of view. The finding of Karran & Williams (1985) that O1mG delivered to cells in culture resulted in the depletion of the activity of the protein responsible for repair of O1mG in DNA (O1mG-DNA methyltransferase, O1MT) provided a tool for the assessment of the role of O1mG in producing biological endpoints. In this paper we review much of the literature on human cells pertinent to this question. In addition we present our survival data obtained using the depletion technique of Karran & Williams as well as data supporting a model invoking a mismatch and excision response to O1mG proposed by Sklar & Strauss (1980). Although data linking O1mG to causation are inconclusive, it is premature to conclude that O1mG is not a lesion lethal to certain cultured cells.
Cellulose microfibril assembly and orientation: recent developments
Authors: Brown R. Malcolm 
Published: May 2013

ABSTRACT
A brief history of the literature dealing with cellulose microfibril assembly is presented, and a current summary of cellulose microfibril synthesizing complexes among eukaryotic cells is given. Terminal complexes not described before include the following: linear terminal complexes (TCs) with three rows in Eremosphaera, Microdictyon and Chaetomorpha’, globular terminal complexes in Ophioglossum, Psilotum, Equisetum and Gingko. Cellulose microfibril assembly in Acetobacter xylinum is described very briefly and compared with the process among eukaryotic cells. Particular emphasis on structures that may be involved in the spatial control of cellulose synthesis is given i Among these are cytoplasmic structures such as microtubules and microfilaments. Microfilament structures are shown to clearly surround individual microtubules that lie adjacent to the plasma membrane. Using freeze-fracture techniques, these labile associations have been shown for the first time. Microfibril orientation may be mediated through an interaction of cortical microtubules in association with microfilaments. A review of Mueller and Brown’s membrane flow model for microfibril orientation is presented. Cellulose terminal complex clustering and its role in gravitropic response is covered. Definitive membrane changes with TC clustering/disaggregation and intramembranous particle frequencies, occur within 12 min following gravistimulation. These differences are pronounced in the cells from upper and lower hemicylinders of rapidly frozen tissue, which was studied by the freeze-fracture method. A hypothesis for cellulose microfibril interaction in controlling the constraint of the growth axis is presented, and the supporting data for terminal complex clustering/disaggregation as well as fluorescent brightener inhibition of the gravitropic response support this hypothesis. The onset and regulation of cellulose microfibril assembly is presented for synchronized protoplasts generated by Boergesenia, using inhibitors of transcription and translation. These results suggest dynamic turnover of terminal complex subunits during the assembly of the cellulose microfibril. This study is concluded with a brief discussion of possible phylogenetic trends in the evolution of cellulose synthesis. A principal underlying theme is that the specific arrangement and consolidation of the terminal complex subunits determine to a large degree the size and shape of the microfibril, its crystallinity, as well as intramicrofibrillar associations. Three basic types of TCs appear among all eukaryotic cells studied so far: namely, the rosette, the globular and the linear complex.
Molecular dissection of the human transferrin receptor
Authors: Schneider Claudio , Williams J. G. 
Published: May 2013

ABSTRACT
Transferrin is the major iron carrier protein in vertebrates and is required for maintenance of cell viability. To deliver iron, transferrin binds to its receptor, the complex is internalized and directed into acidic vacuoles where iron is dissociated and the ligand-receptor complex is recycled back to the plasma membrane. The transferrin receptor is a transmembrane glycoprotein, composed of two disulphide-bonded subunits (each of apparent Mr 90000). It contains three N-linked glycan units and is post-translationally modified with both phosphate and fatty-acyl groups. The primary structure of the receptor consists of 760 amino acids divided into three domains. Starting from the N-terminal residue the cytoplasmic domain consists of 62 amino acids, followed by 26 predominantly non-polar residues, which constitute the transmembrane domain, and 672 residues form the C-terminal extracellular domain. It does not contain an N-terminal cleavable signal sequence.
Synergistic signals in mitogenesis: role of ion fluxes, cyclic nucleotides and protein kinase c in swiss 3t3 cells
Authors: Rozengurt Enrique , Mendoza Stanley A. 
Published: May 2013

ABSTRACT
A fundamental feature in the action of most mitogenic agents when added to quiescent cells in serum-free medium is that they exhibit striking synergistic effects when applied in specific combinations. A tenable hypothesis of growth control must provide a cogent explanation for the molecular mechanisms underlying this complex pattern of synergistic effects. To gain an understanding of the mechanisms by which these synergistic effects arise, we studied the initial cellular responses associated with the interaction of mitogenic factors and hormones with the cell, including changes in cation fluxes, cyclic nucleotides and cellular phosphoproteins. In this paper, some of our recent results on the early signals and responses elicited by multiple growth-promoting agents in quiescent cultures of Swiss 3T3 cells will be summarized. On the basis of the emerging information, we propose a framework that integrates early events and synergistic effects in a unified hypothesis of growth control.
Production of epidermal growth factor in ESCHERICHIA COLI from a synthetic gene
Authors: Allen Geoffrey , Paynter Cora A. , Winther Michael D. 
Published: May 2013

ABSTRACT
Mouse epidermal growth factor (EGF) is under investigation as a defleecing agent for sheep. Substantial quantities of the pure protein are required for these studies and to supply this need a gene for the protein was synthesized and inserted into plasmid vectors to direct the expression of EGF polypeptide, or fusion proteins containing the EGF peptide sequence, in transformed Escherichia coli. Mature EGF was released by lysine specific proteolysis of a fusion protein consisting of part of theE. coli TrpE protein, a lysine linker and EGF polypeptide. The EGF was purified and characterized and was found to be biologically active.
Insulin-like growth factor receptors
Authors: Nissley S. Peter , Haskell Joyce F. , Sasaki Norio , Vroede Monique A. De , Rechler Matthew M. 
Published: May 2013

ABSTRACT
There are two types of insulin-like growth factor (IGF) receptors. The type I receptor generally binds IGF-I more tightly than IGF-II and also interacts weakly with insulin. The type II receptor prefers IGF-II over IGF-I and does not recognize insulin. The type I receptor is made up of an alpha binding subunit (Mr 130000) and a beta subunit (Mr 95 000) probably organized as a heterotetramer (α2β2). The type II receptor consists of a single binding unit (Mr 250000). IGF stimulates phosphorylation of the beta subunit of the type I receptor in whole cells and solubilized receptor preparations. Tyrosine kinase activity is associated with the type I receptor, resulting in autophosphorylation of the beta subunit and phosphorylation of exogenous substrates. In contrast, phosphorylation of the type II receptor in whole cells is less IGF-dependent, solubilized receptor preparations are not phosphorylated, and purified type II receptors do not exhibit tyrosine kinase activity toward the artificial substrate poly(Glu,Tyr)4:1. There are many similarities between the type I IGF receptor and the insulin receptor; however, different ligand-binding properties, subtle differences in the size of alpha and beta subunits, and immunoreactivity toward anti-receptor antibodies allow us to distinguish between these two receptors. The presence of both IGF receptors as well as insulin receptors on most cells and cross-reactivity of ligands for binding to these receptors present difficulties in assigning a particular biological response to a specific receptor. The type I receptor is down-regulated by ligand while in several cell types the type II receptor is rapidly up-regulated by insulin; the mechanism of up-regulation appears to be a translocation of type II receptors to the cell surface. There are two classes of serum binding proteins for IGF, a Mr 150 000 species found in adult blood and a Mr 40 000 species, which predominates in foetal blood. Like the type II receptor, IGF binding proteins do not bind insulin. The binding site on the type II receptor can be distinguished from the binding protein sites by a hybrid molecule Ainsulin-BIDF-I, which recognizes the binding protein but not the type II receptor. Binding proteins produced by cells in culture may cause confusion in the interpretation of experiments that are designed to study the binding of radiolabelled IGF to cell surface receptors in monolayer culture.
Platelet-derived growth factor: mechanism of action and relation to oncogenes
Authors: Heldin C.-H. , Betsholtz C. , Johnsson A. , Nistér M. , Ek B. , Rönnstrand L. , Wasteson Å. , Westermark B. 
Published: May 2013

ABSTRACT
Recent studies of platelet-derived growth factor (PDGF) have revealed several structural and functional similarities between this growth factor or components linked to its mechanism of action and certain oncogene products: PDGF itself has a structural homology with the transforming protein of simian sarcoma virus, the PDGF receptor has a functional homology (tyrosine kinase activity) with a family of oncogene products, and PDGF induces the expression of the cellular counterparts of myc and fos. In addition, several tumour cell lines have been found to produce PDGF-like growth factors, which may cause autocrine stimulation of growth. We interpret these findings as indicating that regulatory components along the PDGF-dependent mitogenic pathway may have oncogenic properties if they are inappropriately expressed or activated.
Dynein Structure And Function
Authors: A. Johnson Kenneth , P. Marchese-Ragona Silvio , B. Clutter Daniel , F. Holzbaur Erika L. , J. Chilcote Tamie 
Published: May 2013

ABSTRACT
The structure of dynein isolated from several sources follows the pattern first observed with Tetrahymena 22 S dynein, which has three globular heads attached by three flexible strands to a root-like base. Recent biochemical data indicate that there is one ATPase site on each dynein head and that all three heads interact with microtubules in an ATP-sensitive manner. Accordingly, images of dynein in situ can be interpreted in terms of a model for crossbridge action where the roots of the bouquet anchor the dynein to the A-tubule and all three heads reach out to interact with the B-tubule in an ATP-dependent reaction to produce a force for sliding.
Mutations Affecting Microtubule Structure In Caenorhabditis Elegans
Authors: Chalfie Martin , Dean Ellen , Reilly Evelyn , Buck Kay , Nichol Thomson J. 
Published: May 2013

ABSTRACT
Three types of microtubules are seen in the neuronal processes of the nematode Caenorhabditis elegans. Single cytoplasmic microtubules of most neurones have 11 protofilaments whereas those of six touch receptor cells have 15 protofilaments. The axonemes of sensory cilia have nine outer doublets with a variable number (up to seven) of singlet microtubules. Mutations in 11 genes affect the appearance of these microtubules.