bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Bacterial Gene Encoding Capsule Biosynthesis Protein CapI Contains Nucleotides Derived from Exonization
Authors: Wang Yong , Tao Xia-Fang , Su Zhi-Xi , Liu A-Ke , Liu Tian-Lei , Sun Ling , Yao Qin , Chen Ke-Ping , Gu Xun
Published: November 2017

Since the proposition of introns-early hypothesis, although many studies have shown that most eukaryotic ancestors possessed intron-rich genomes, evidence of intron existence in genomes of ancestral bacteria has still been absent. While not a single intron has been found in all protein-coding genes of current bacteria, analyses on bacterial genes horizontally transferred into eukaryotes at ancient time may provide evidence of intron existence in bacterial ancestors. In this study, a bacterial gene encoding capsule biosynthesis protein CapI was found in the genome of sea anemone, Nematostella vectensis. This horizontally transferred gene contains a phase 1 intron of 40 base pairs. The nucleotides of this intron have high sequence identity with those encoding amino acids in current bacterial CapI gene, indicating that the intron and the amino acid-coding nucleotides are originated from the same ancestor sequence. Moreover, 5'-splice site of this intron is located in a GT-poor region associated with a closely following AG-rich region, suggesting that deletion mutation at 5'-splice site has been employed to remove this intron and the intron-like amino acid-coding nucleotides in current bacterial CapI gene are derived from exonization. These data suggest that bacterial CapI gene contained intron(s) at ancient time. This is the first report providing the result of sequence analysis to suggest possible existence of spliceosomal introns in ancestral bacterial genes. The methodology employed in this study may be used to identify more such evidence that would aid in settlement of the dispute between introns-early and introns-late theories.
Dissection of Functional Residues in Receptor Activity-Modifying Proteins through Phylogenetic and Statistical Analyses
Authors: Benítez-Páez Alfonso , Cárdenas-Brito Sonia
Published: November 2017

Type I and type-II functional divergences have been stated to highlight specific residues carrying out differential functions in evolutionary-divergent protein clusters from a single common ancestor. Briefly, type I analysis is based on residue constraints reflecting a gain of function just in one cluster of an entire family of proteins; while the type-II approach is based on residue constraints showing a different chemical nature in every cluster of a protein family. This last evidence is understood as differential functionality among clusters. The Receptor Activity-Modifying Proteins constitute a family characterized by its paralogous distribution in vertebrates. They are known as G-Protein Coupled Receptor modulators. Although several studies have determined their involvement in ligand binding, specificity, and enhancement of signal transduction, the responsible residues supporting those functions are unclear. Using different bioinformatic approaches, we predicted residues involved in different RAMP functional tasks. Many residues localized in an extracellular coil of RAMP proteins were predicted to be under functional divergence suggesting a gain of function in their respective proteins. Interestingly, the transmembrane region also showed important results for residues playing relevant roles where most of them showed a biased distribution on the structure. A relevant role was conferred by the enrichment of type-II residues observed in their sequences. We show a collection of residues explaining possible gain of function and differential functionality in RAMP proteins. These residues are still experimentally unexplored with regards to functionality. Finally, an evolutionary history could be discerned. Mainly, the RAMP2 cluster has evolved in a higher manner than other RAMP clusters. However, a deacceleration in the aminoacid substitution rate of RAMP2 was observed in mammals. Such effect could be caused by the co-evolution of ligands and receptors interacting with RAMP2 through evolution and/or the specialization of this cluster in GPCR modulation.
Estimation of Genetic Effects and Genotype-Phenotype Maps
Authors: Le Rouzic Arnaud , Álvarez-Castro José M.
Published: November 2017

Determining the genetic architecture of complex traits is a necessary step to understand phenotypic changes in natural, experimental and domestic populations. However, this is still a major challenge for modern genetics, since the estimation of genetic effects tends to be complicated by genetic interactions, which lead to changes in the effect of allelic substitutions depending on the genetic background. Recent progress in statistical tools aiming to describe and quantify genetic effects meaningfully improves the efficiency and the availability of genotype-to-phenotype mapping methods. In this contribution, we facilitate the practical use of the recently published ‘NOIA’ quantitative framework by providing an implementation of linear and multilinear regressions, change of reference operation and genotype-to-phenotype mapping in a package (‘noia’) for the software R, and we discuss theoretical and practical benefits evolutionary and quantitative geneticists may find in using proper modeling strategies to quantify the effects of genes.
Bayesian, Maximum Parsimony and UPGMA Models for Inferring the Phylogenies of Antelopes Using Mitochondrial Markers
Authors: Khan Haseeb A. , Arif Ibrahim A. , Bahkali Ali H. , Farhan Ahmad H. Al , Homaidan Ali A. Al
Published: November 2017

This investigation was aimed to compare the inference of antelope phylogenies resulting from the 16S rRNA, cytochrome-b (cyt-b) and d-loop segments of mitochondrial DNA using three different computational models including Bayesian (BA), maximum parsimony (MP) and unweighted pair group method with arithmetic mean (UPGMA). The respective nucleotide sequences of three Oryx species ( Oryx leucoryx, Oryx dammah and Oryx gazella) and an out-group ( Addax nasomaculatus) were aligned and subjected to BA, MP and UPGMA models for comparing the topologies of respective phylogenetic trees. The 16S rRNA region possessed the highest frequency of conserved sequences (97.65%) followed by cyt-b (94.22%) and d-loop (87.29%). There were few transitions (2.35%) and none transversions in 16S rRNA as compared to cyt-b (5.61% transitions and 0.17% transversions) and d-loop (11.57% transitions and 1.14% transversions) while comparing the four taxa. All the three mitochondrial segments clearly differentiated the genus Addax from Oryx using the BA or UPGMA models. The topologies of all the gamma-corrected Bayesian trees were identical irrespective of the marker type. The UPGMA trees resulting from 16S rRNA and d-loop sequences were also identical ( Oryx dammah grouped with Oryx leucoryx) to Bayesian trees except that the UPGMA tree based on cyt-b showed a slightly different phylogeny ( Oryx dammah grouped with Oryx gazella) with a low bootstrap support. However, the MP model failed to differentiate the genus Addax from Oryx. These findings demonstrate the efficiency and robustness of BA and UPGMA methods for phylogenetic analysis of antelopes using mitochondrial markers.
PhyloMarker–-A Tool for Mining Phylogenetic Markers through Genome Comparison: Application of the Mouse Lemur (Genus Microcebus) Phylogeny
Authors: Lei Runhua , Rowley Thaine W. , Zhu Lifeng , Bailey Carolyn A. , Engberg Shannon E. , Wood Mindy L. , Christman Mary C. , Perry George H. , Louis Edward E. , Lu Guoqing
Published: November 2017

Molecular phylogeny is a fundamental tool to understanding the evolution of all life forms. One common issue faced by molecular phylogeny is the lack of sufficient molecular markers. Here, we present PhyloMarker, a phylogenomic tool designed to find nuclear gene markers for the inference of phylogeny through multiple genome comparison. Around 800 candidate markers were identified by PhyloMarker through comparison of partial genomes of Microcebus and Otolemur. In experimental tests of 20 randomly selected markers, nine markers were successfully amplified by PCR and directly sequenced in all 17 nominal Microcebus species. Phylogenetic analyses of the sequence data obtained for 17 taxa and nine markers confirmed the distinct lineage inferred from previous mtDNA data. PhyloMarker has also been used by other projects including the herons (Ardeidae, Aves) phylogeny and the Wood mice (Muridae, Mammalia) phylogeny. All source code and sample data are made available at http://bioinfo-srv1.awh.unomaha.edu/phylomarker /.
Article Commentary: Autism Spectrum Disorders and Identified Toxic Land Fills: Co-Occurrence across States
Authors: Ming Xue , Brimacombe Michael , Malek Joanne H. , Jani Nisha , Wagner George C.
Published: November 2017

It is believed that gene by environmental interactions contribute to the pathogenesis of autism spectrum disorders (ASD). We hypothesize that ASD are associated with early and repeated exposures to any of a number of toxicants or mixtures of toxicants. It is the cumulative effects of these repeated exposures acting upon genetically susceptible individuals that lead to the phenotypes of ASD. We report our initial observations of a considerable overlap of identified toxic landfills in the State of New Jersey and the residence of an ASD cohort, and a correlation between the identified toxic Superfund sites on each U.S. state and the total number of diagnosed cases of ASD in those states. The residence of 495 ASD patients in New Jersey by zip code and the toxic landfill sites were plotted on a map of Northern New Jersey. The area of highest ASD cases coincides with the highest density of toxic landfill sites while the area with lowest ASD cases has the lowest density of toxic landfill sites. Furthermore, the number of toxic Superfund sites and autism rate across 49 of the 50 states shows a statistically significant correlation (i.e. the number of identified superfund sites correlates with the rate of autism per 1000 residents in 49 of the states (p = 0.015; excluding the state of Oregon). These significant observations call for further organized studies to elucidate possible role(s) of environmental toxicants contributing to the pathogenesis of ASD.
The Gravitation of the Moon Plays Pivotal Roles in the Occurrence of the Acute Myocardial Infarction
Authors: Wake Ryotaro , Yoshikawa Junichi , Haze Kazuo , Otani Shinichiro , Yoshimura Takayoshi , Toda Iku , Nishimoto Masaki , Kawarabayashi Takahiko , Tanaka Atsushi , Shimada Kenei , Iida Hidetaka , Takeuchi Kazuhide , Yoshiyama Minoru
Published: November 2017

Acute myocardial infarction (AMI) is a social burden. However, being able to predict AMI could lead to prevention. A previous study showed only the relation between the lunar phase and the occurrence of AMI, but the period it takes for the moon to orbit around the earth and the period of the lunar phase differ. This study investigated the effect of the gravitation of the moon on AMI. Data was comprised of 1369 consecutive patients with first AMI at 5 hospitals from October, 1984 to December, 1997. The universal gravitation of the moon was calculated and compared to the earth onset time of AMI. Universal gravitation of the moon was derived by G*m/d2 (G: universal gravitation constant, m: the mass of the moon, d: the distance between the center of the moon and the center of the earth). The relationship between m/d2 and the cases of AMI was determined. There was an increase in cases, when there is a distance of more than 399864 km from the center of the earth to the center of the moon. The gravitation of more than 399864 km was determined to be weaker gravitation. It is confirmed that the number of AMI patients significantly increases at weaker gravitation periods in this multicenter trial. In conclusion, these results suggest that the gravitation of the moon may have an influence on the occurrence of AMI.
Article Commentary: Just how Big is the Schism between the Health Sector and the Water and Sanitation Sector in Developing Countries?
Authors: Cronin A. A. , Pond K.
Published: November 2017

Water, sanitation and hygiene are all key aspects to a healthy environment but often they suffer from a lack of coherence within the sector itself and also a lack of synergy with the health sector. This is not acceptable given one quarter of all child deaths are directly attributable to water-borne disease. This lack of synergy is evident at many different layers including planning, resource allocation and donor commitment. Developing countries must, in consultation with their communities, examine their biggest health risks and allocate resources accordingly. Sustained dialogue and increased in-depth analysis are needed to find consensus and an improved synergy across these vital sectors.
An Effective Tri-Clustering Algorithm Combining Expression Data with Gene Regulation Information
Authors: Li Ao , Tuck David
Published: November 2017

Motivation

Bi-clustering algorithms aim to identify sets of genes sharing similar expression patterns across a subset of conditions. However direct interpretation or prediction of gene regulatory mechanisms may be difficult as only gene expression data is used. Information about gene regulators may also be available, most commonly about which transcription factors may bind to the promoter region and thus control the expression level of a gene. Thus a method to integrate gene expression and gene regulation information is desirable for clustering and analyzing.

Methods

By incorporating gene regulatory information with gene expression data, we define regulated expression values (REV) as indicators of how a gene is regulated by a specific factor. Existing bi-clustering methods are extended to a three dimensional data space by developing a heuristic TRI-Clustering algorithm. An additional approach named Automatic Boundary Searching algorithm (ABS) is introduced to automatically determine the boundary threshold.

Results

Results based on incorporating ChIP-chip data representing transcription factor-gene interactions show that the algorithms are efficient and robust for detecting tri-clusters. Detailed analysis of the tri-cluster extracted from yeast sporulation REV data shows genes in this cluster exhibited significant differences during the middle and late stages. The implicated regulatory network was then reconstructed for further study of defined regulatory mechanisms. Topological and statistical analysis of this network demonstrated evidence of significant changes of TF activities during the different stages of yeast sporulation, and suggests this approach might be a general way to study regulatory networks undergoing transformations.
Post-Transcriptional Control of Chloroplast Gene Expression
Authors: Del Campo Eva M.
Published: November 2017

Chloroplasts contain their own genome, organized as operons, which are generally transcribed as polycistronic transcriptional units. These primary transcripts are processed into smaller RNAs, which are further modified to produce functional RNAs. The RNA processing mechanisms remain largely unknown and represent an important step in the control of chloroplast gene expression. Such mechanisms include RNA cleavage of pre-existing RNAs, RNA stabilization, intron splicing, and RNA editing. Recently, several nuclear-encoded proteins that participate in diverse plastid RNA processing events have been characterised. Many of them seem to belong to the pentatricopeptide repeat (PPR) protein family that is implicated in many crucial functions including organelle biogenesis and plant development. This review will provide an overview of current knowledge of the post-transcriptional processing in chloroplasts.
Sigma Factors for Cyanobacterial Transcription
Authors: Imamura Sousuke , Asayama Munehiko
Published: November 2017

Cyanobacteria are photosynthesizing microorganisms that can be used as a model for analyzing gene expression. The expression of genes involves transcription and translation. Transcription is performed by the RNA polymerase (RNAP) holoenzyme, comprising a core enzyme and a sigma (σ) factor which confers promoter selectivity. The unique structure, expression, and function of cyanobacterial σ factors (and RNAP core subunits) are summarized here based on studies, reported previously. The types of promoter recognized by the σ factors are also discussed with regard to transcriptional regulation.
Proposed Regulation of Gene Expression by Glucose in Rodent Heart
Authors: Young Martin E. , Yan Jie , Razeghi Peter , Cooksey Robert C. , Guthrie Patrick H. , Stepkowski Stanislaw M. , McClain Donald A. , Tian Rong , Taegtmeyer Heinrich
Published: November 2017

Background

During pressure overload-induced hypertrophy, unloading-induced atrophy, and diabetes mellitus, the heart induces ‘fetal’ genes (e.g. myosin heavy chain β; mhcβ).

Hypothesis

We propose that altered glucose homeostasis within the cardiomyocyte acts as a central mechanism for the regulation of gene expression in response to environmental stresses. The evidence is as follows.

Methods and Results

Forced glucose uptake both ex vivo and in vivo results in mhc isoform switching. Restricting dietary glucose prevents mhc isoform switching in hearts of both GLUT1-Tg mice and rats subjected to pressure overload-induced hypertrophy. Thus, glucose availability correlates with mhc isoform switching under all conditions investigated. A potential mechanism by which glucose affects gene expression is through O-linked glycosylation of specific transcription factors. Glutamine:fructose-6-phosphate amidotransferase (GFAT) catalyzes the flux generating step in UDP-N-acetylglucosamine biosynthesis, the rate determining metabolite in protein glycosylation. Ascending aortic constriction increased intracellular levels of UDP-N-acetylglucosamine, and the expression of gfat2, but not gfat1, in the rat heart.

Conclusions

Collectively, the results strongly suggest glucose-regulated gene expression in the heart, and the involvement of glucose metabolites in isoform switching of sarcomeric proteins characteristic for the fetal gene program.
Application of Petri Nets in Bone Remodeling
Authors: Li Lingxi , Yokota Hiroki
Published: November 2017

Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs) have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs), which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.
Evaluation of the Role of FGF23 in Mineral Metabolism
Authors: Yokota Hiroki , Raposo João F. , Chen Andy , Jiang Chang , Ferreira Hugo G.
Published: November 2017

Fibroblast growth factor 23 (FGF23) has recently been identified as a critical regulatory factor in phosphate (P) metabolism. Although the exact molecular mechanism of FGF23 synthesis through sensing the concentration of P is yet to be determined, experimental and clinical data indicate the influential role of FGF23 in P and calcium (Ca) homeostasis. Here, we extended our previous mathematical model in calcium regulation and examined the conceivable roles of FGF23 in mineral metabolism. We assumed that the level of FGF23 was controlled through the concentrations of P and calcitriol in serum, and its actions such as lowering of the renal threshold for P, inhibition of the production of calcitriol in the kidney tubule, and inhibition of the production of parathyroid hormone (PTH) were included. Comparisons between the models with and without FGF23 demonstrate a complex interplay of FGF23 with calcitriol and PTH. In consistent with the model, our in vitro experimentation indicates that expression of FGF23 is activated in the presence of P though a G-protein linked receptor. We expect that further efforts on modeling and experimental evaluation would contribute to diagnosing patients with metabolic diseases such as osteoporosis and chronic kidney diseases, and developing FGF23-linked treatment strategies.
Article Commentary: Microarray Data Analysis of Gene Expression Evolution
Authors: Lin Honghuang
Published: November 2017

Microarrays are becoming a widely used tool to study gene expression evolution. A recent paper by Wang and Rekaya describes a comprehensive study of gene expression evolution by microarray. 1 The work provides a perspective to study gene expression evolution in terms of functional enrichment and promoter conservation. It was found that gene expression patterns are highly conserved in some biological processes, but the correlation between promoter and gene expression is insignificant. This scope of this work and future improvement to study gene expression evolution will be discussed in this article.
Characteristics of Transcriptional Activity in Nonlinear Dynamics of Genetic Regulatory Networks
Authors: Rosenfeld Simon
Published: November 2017

Microarray measurements of mRNA abundances is a standard tool for evaluation of transcriptional activity in functional genomics. The methodology underlying these measurements assumes existence of a direct link between transcription levels, that is, gene-specific mRNA copy numbers present in the cell, and transcription rates, that is, the numbers of gene-specific mRNA molecules synthesized per unit of time. In this paper, the question of whether or not such a tight interdependence may exist is examined in the context of nonlinear dynamics of genetic regulatory networks. Using the equations of chemical kinetics, a model has been constructed that is capable of explicitly taking into consideration nonlinear interactions between the genes through the teamwork of transcription factors. Jacobian analysis of stability has shown that steady state equilibrium is impossible in such systems. However, phase space compressibility is found to be negative, thus suggesting that asymptotic stability may exist and assume either the form of limit cycle or of a chaotic attractor. It is argued that in rapidly fluctuating or chaotic systems, direct evaluation of transcription rates through transcription levels is highly problematic. It is also noted that even if a hypothetical steady state did exist, the knowledge of transcription levels alone would not be sufficient for the evaluation of transcription rates; an additional set of parameters, namely the mRNA decay rates, would be required. An overall conclusion of the work is that the measurements of mRNA abundances are not truly representative of the functionality of genes and structural fidelity of the genetic codes.
Gene Expression Analysis of Biological Systems Driving an Organotypic Model of Endometrial Carcinogenesis and Chemoprevention
Authors: Benbrook Doris M. , Lightfoot Stan , Ranger-Moore James , Liu Tongzu , Chengedza Shylet , Berry William L. , Dozmorov Igor
Published: November 2017

An organotypic model of endometrial carcinogenesis and chemoprevention was developed in which normal endometrial organotypic cultures exposed to the carcinogen, DMBA (7,12-dimethylbenz[a]anthracene), developed a cancerous phenotype in the absence, but not presence of subsequent treatment with a flexible heteroarotinoid (Flex-Het), called SHetA2. A discriminant function based on karyometric features of cellular nuclei and an agar clonogenic assay confirmed these histologic changes. Interpretation of microarray data using an internal standard approach identified major pathways associated with carcinogenesis and chemoprevention governed by c-myc, p53, TNFα and Jun genes. Cluster analysis of functional associations of hypervariable genes demonstrated that carcinogenesis is accompanied by a stimulating association between a module of genes that includes tumor necrosis factor α (TNFα), c-myc, and epidermal growth factor-receptor (EGF-R) and a module that includes insulin-like growth factor I-receptor (IGF-IR), p53, and Jun genes. Two secreted proteins involved in these systems, tenascin C and inhibin A, were validated at the protein level. Tenascin C is an EGF-R ligand, and therefore may contribute to the increased EGF-R involvement in carcinogenesis. The known roles of the identified molecular systems in DMBA and endometrial carcinogenesis and chemoprevention supports the validity of this model and the potential clinical utility of SHetA2 in chemoprevention.
Signaling Mechanisms of Endogenous Angiogenesis Inhibitors Derived from Type IV Collagen
Authors: Sudhakar Akulapalli , Boosani Chandra S.
Published: November 2017

Vascular basement membrane (VBM) derived molecules are regulators of certain biological activities such as cell growth, differentiation and angiogenesis. Angiogenesis is regulated by a systematic controlled balance between VBM derived antiangiogenic factors and proangiogenic growth factors. In the normal physiological state, equilibrium is maintained between the antiangiogenic and proangiogenic factors. The antiangiogenic factors (molecules), which are generated by the proteolytic cleavage of the VBM, include; α1 chain non-collagenous (NC1) domain of type XVIII collagen (endostatin) and the NC1 domains from the alpha chains of Type IV collagen considered as endogenous angiogenesis inhibitors. These collagen derived NC1 domains have a pivotal role in the regulation of tumor angiogenesis, thus making them attractive alternate candidates for cancer therapies. In this review we illustrate a comprehensive overview of the knowledge gained from the signaling mechanisms of Type IV collagen derived endogenous inhibitors in angiogenesis.
MicroRNA Expression in Alzheimer Blood Mononuclear Cells
Authors: Schipper Hyman M. , Maes Olivier C. , Chertkow Howard M. , Wang Eugenia
Published: November 2017

Various coding genes representing multiple functional categories are downregulated in blood mononuclear cells (BMC) of patients with sporadic Alzheimer disease (AD). Noncoding microRNAs (miRNA) regulate gene expression by degrading messages or inhibiting translation. Using BMC as a paradigm for the study of systemic alterations in AD, we investigated whether peripheral miRNA expression is altered in this condition. MicroRNA levels were assessed using the microRNA microarray (MMChip) containing 462 human miRNA, and the results validated by real time PCR. Sixteen AD patients and sixteen normal elderly controls (NEC) were matched for ethnicity, age, gender and education. The expression of several BMC miRNAs was found to increase in AD relative to NEC levels, and may differ between AD subjects bearing one or two APOE4 alleles. As compared to NEC, miRNAs significantly upregulated in AD subjects and confirmed by qPCR were miR-34a and 181b. Predicted target genes downregulated in Alzheimer BMC that correlated with the upregulated miRNAs were largely represented in the functional categories of Transcription/Translation and Synaptic Activity. Several miRNAs targeting the same genes were within the functional category of Injury response/Redox homeostasis. Taken together, induction of microRNA expression in BMC may contribute to the aberrant systemic decline in mRNA levels in sporadic AD.
Identifying Cell Type-Specific Transcription Factors by Integrating ChIP-seq and eQTL Data-Application to Monocyte Gene Regulation
Authors: Choudhury Mudra , Ramsey Stephen A.
Published: November 2017

We describe a novel computational approach to identify transcription factors (TFs) that are candidate regulators in a human cell type of interest. Our approach involves integrating cell type-specific expression quantitative trait locus (eQTL) data and TF data from chromatin immunoprecipitation-to-tag-sequencing (ChIP-seq) experiments in cell lines. To test the method, we used eQTL data from human monocytes in order to screen for TFs. Using a list of known monocyte-regulating TFs, we tested the hypothesis that the binding sites of cell type-specific TF regulators would be concentrated in the vicinity of monocyte eQTLs. For each of 397 ChIP-seq data sets, we obtained an enrichment ratio for the number of ChIP-seq peaks that are located within monocyte eQTLs. We ranked ChIP-seq data sets according to their statistical significances for eQTL overlap, and from this ranking, we observed that monocyte-regulating TFs are more highly ranked than would be expected by chance. We identified 27 TFs that had significant monocyte enrichment scores and mapped them into a protein interaction network. Our analysis uncovered two novel candidate monocyte-regulating TFs, BCLAF1 and SIN3A. Our approach is an efficient method to identify candidate TFs that can be used for any cell/tissue type for which eQTL data are available.
Image Analysis and Data Normalization Procedures are Crucial for Microarray Analyses
Authors: Kadanga Ali Kpatcha , Leroux Christine , Bonnet Muriel , Chauvet Stéphanie , Meunier Bruno , Cassar-Malek Isabelle , Hocquette Jean-François
Published: November 2017

This study was conducted with the aim of optimizing the experimental design of array experiments. We compared two image analysis and normalization procedures prior to data analysis using two experimental designs. For this, RNA samples from Charolais steers Longissimus thoracis muscle and subcutaneous adipose tissues were labeled and hybridized to a bovine 8,400 oligochip either in triplicate or in a dye-swap design. Image analysis and normalization were processed by either GenePix/MadScan or ImaGene/GeneSight. Statistical data analysis was then run using either the SAM method or a Student's t-test using a multiple test correction run on R 2.1 software. Our results show that image analysis and normalization procedure had an impact whereas the statistical methods much less influenced the outcome of differentially expressed genes. Image analysis and data normalization are thus an important aspect of microarray experiments, having a potentially significant impact on downstream analyses such as the identification of differentially expressed genes. This study provides indications on the choice of raw data preprocessing in microarray technology.
Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics
Authors: Mansoor Moizza , Melendez Alirio J.
Published: November 2017

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.
Gene Regulation System of Vasopressin and Corticotoropin-Releasing Hormone
Authors: Yoshida Masanori
Published: November 2017

The neurohypophyseal hormones, arginine vasopressin and corticotropin-releasing hormone (CRH), play a crucial role in the physiological and behavioral response to various kinds of stresses. Both neuropeptides activate the hypophysial-pituitary-adrenal (HPA) axis, which is a central mediator of the stress response in the body. Conversely, they receive the negative regulation by glucocorticoid, which is an end product of the HPA axis. Vasopressin and CRH are closely linked to immune response; they also interact with pro-inflammatory cytokines. Moreover, as for vasopressin, it has another important role, which is the regulation of water balance through its potent antidiuretic effect. Hence, it is conceivable that vasopressin and CRH mediate the homeostatic responses for survival and protect organisms from the external world. A tight and elaborate regulation system of the vasopressin and CRH gene is required for the rapid and flexible response to the alteration of the surrounding environments. Several important regulatory elements have been identified in the proximal promoter region in the vasopressin and CRH gene. Many transcription factors and intracellular signaling cascades are involved in the complicated gene regulation system. This review focuses on the current status of the basic research of vasopressin and CRH. In addition to the numerous known facts about their divergent physiological roles, the recent topics of promoter analyses will be discussed.
Butyrate Induced Cell Cycle Arrest in Bovine Cells through Targeting Gene Expression Relevant to DNA Replication Apparatus
Authors: Li Cong-jun , Li Robert W.
Published: November 2017

Using real-time RT-PCR and Western blot analysis in bovine kidney epithelial cells, we systematically investigated the effects of butyrate on patterns of gene expression relevant to DNA replication apparatus. The real-time PCR and Western blot data generally confirmed previously reported microarray data. Of the five genes tested by quantitative RT-PCR, CDKN1A (p21waf1) was up regulated, CDC2/cdk1, MCM6, ORC1L were down regulated, while ORC3L expression remained unchanged following butyrate treatment. Also consistent with RT-PCR results, Western blot analysis confirmed that butyrate up-regulated cyclin-kinase inhibitor p21waf1 in a does-dependent manner. In contrast, butyrate treatment had no effect on the expression of ERK 1/2 proteins. Also consistent with mRNA results, ORC1 and MCM3 proteins were down-regulated by butyrate treatment, while ORC2 protein remained unchanged. The present results suggest that ORC1, not ORC2 or ORC3, along with MCM proteins play a critical role in regulating the initiation of DNA replication and cell cycle progression in MDBK cells and are targets of butyrate regulation.
Multi-Target Approaches in Colon Cancer Chemoprevention Based on Systems Biology of Tumor Cell-Signaling
Authors: Guruswamy Suresh , Rao Chinthalapally V.
Published: November 2017

Colorectal cancer is the leading cause of cancer related deaths in the United States. Although it is preventable, thousands of lives are lost each year in the U.S. to colorectal cancer than to breast cancer and AIDS combined. In colon cancer, the formation and progression of precancerous lesions like aberrant crypt foci and polyps is associated with the up-regulation of cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and hydroxy methyl glutaryl CoA reductase (HMG-CoA reductase). The current review will focus on the signaling pathway involving COX-2 and HMG-CoA reductase enzymes and their downstream effectors in signaling mechanism. Cancer cells need huge pools of both cholesterol and isoprenoids to sustain their unlimited growth potential. Cholesterol by modulating caveolae formation regulates several signaling molecules like AKT, IGFR, EGFR and Rho which are involved in cell growth and survival. Cholesterol is also essential for lipid body formation which serves as storage sites for COX-2, eicosanoids and caveolin-1. Experimental studies have identified important mechanisms showing that COX-2, caveolin-1, lipid bodies and prenylated proteins is involved in carcinogenesis. Therefore multi-target, multi-drug approach is the ideal choice for effective colon cancer chemoprevention. This review will give an overview of the two pathways, their signaling networks, and the interactions between the components of the two networks in the activation and regulation of cell signaling involving growth/survival and explain the rationale for colon cancer chemoprevention using COX-2 inhibitors and statins.
Calcitriol and TO-901317 Interact in Human Prostate Cancer LNCaP Cells
Authors: Wang Jing-Huan , Tuohimaa Pentti
Published: November 2017

Vitamin D receptor (VDR) and liver X receptor (LXR) are nuclear receptors, which regulate gene transcription upon binding of their specific ligands. VDR seems to play a role in the regulation of prostate cancer cell proliferation. ATP-binding cassette transporter A1 (ABCA1) is known to be a target gene of LXR and it has been reported to be inhibited by androgen and to be involved in the regulation of LNCaP proliferation. We find that calcitriol (1α,25(OH)2D3) inhibits both basal and a LXR agonist, TO-901317, induced ABCA1 mRNA expression but has no effect on the mRNA expression of ATP-binding cassette transporter G1 (ABCG1), LXRα nor LXRβ TO-901317 increases both basal and calcitriol induced 25-hydroxyvitamin D3-24-hydroxylase (CYP24) mRNA expression and it slightly but significantly inhibits VDR mRNA expression. The inhibition of ABCA1 by calcitriol appears to be androgen-independent. Cell growth assay shows that when each of calcitriol and 5a-dihydrotestosterone (DHT) was co-treated with ABCA1 blocker, glybenclamide, cell-growth is significantly decreased compared to their own treatments respectively. Our study suggests a possible interaction between calcitriol and TO-901317 in LNCaP cells. Alike DHT, the inhibition of ABCA1 by calcitriol may be involved in its regulation of LNCaP growth.
Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle after Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades
Authors: Yao Zhenling , Hoffman Eric P. , Ghimbovschi Svetlana , DuBois Debra C. , Almon Richard R. , Jusko William J.
Published: November 2017

Corticosteroids (CS) effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX) rats were given single doses of 50 mg/kg methylprednisolone (MPL) intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1), uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase isoenzyme 4 (PDK4), fatty acid translocase (FAT) and glycerol-3-phosphate acyltransferase (GPAT) dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N)) and transcription factors. The oscillatory feature of endothelin-1 (ET-1) expression was depicted by a negative feedback loop. These integrated models provide testable quantitative hypotheses for these regulatory cascades.
RNA Processing and mRNA Surveillance in Monogenic Diabetes
Authors: Locke Jonathan M. , Harries Lorna W.
Published: November 2017

In the eukaryotic cell a number of molecular mechanisms exist to regulate the nature and quantity of transcripts intended for translation. For monogenic diabetes an understanding of these processes is aiding scientists and clinicians in studying and managing this disease. Knowledge of RNA processing and mRNA surveillance pathways is helping to explain disease mechanisms, form genotype-phenotype relationships, and identifying new regions within genes to screen for mutations. Furthermore, recent insights into the regulatory role of micro RNAs (miRNAs) and RNA editing in the pancreas suggests that these mechanisms may also be important in the progression to the diabetic state.
Torque-Tension Tightening for Metric Series Fasteners
Authors:   Fasteners Committee
Published: November 2017

This SAE Information Report is provided as an advisory guide. Individual application discretion is recommended. The content has been presented as accurately as possible, but responsibility for its application lies with the user. The document covers a number of the variables in the torque-tension relationship: friction, materials, temperature, humidity, fastener and mating part finishes, surfaces, and the kind of tightening tools or equipment used.

Also described in this document is the torque management required to achieve satisfactory fastened joint tightening.

This guide is limited in application to clearance fit threads, such as the common 6g/6H class of fit. Other thread types including interference fit, mechanical locking, prevailing torque, or forms other than ISO-Metric may apply to some aspects of this standard but are not specifically covered.

The procedures described in this document are based on general principles for the determination of the torque-tension relationship for the use of end users. This is a guide and is not intended to be made a procurement requirement. For critical joint design the assembly torque values should be determined by experimentation using the exact assembly components.
Triclosan: Hazards of Overuse are not limited to Antibiotics
Authors: Bonanthaya Krishnamurthy , Uppal Nakul
Published: November 2017

How to cite this article

Uppal N, Bonanthaya K. Triclosan: Hazards of Overuse are not limited to Antibiotics. J Contemp Dent Pract 2017;18(11):989-990.
Dissolution of Enamel on Exposure to Various Commercial Beverages Available in India
Authors: Dash Kailash C , Panda Abikshyeet , Bhuyan Lipsa , Ghosh Bikramaditya , Pal Imon
Published: November 2017

Aim

The study was aimed to estimate the pH of the commonly available soft drinks in the Indian market and to assess the detrimental effects of the juices and beverages on the tooth surface by measuring the weight loss of the tooth sample.

Materials and methods

The study was done with eight different types of commercially available carbonated drink and fruit juices available in the Indian market among which six were carbonated drinks and two were juices. Carbonated drinks experimented were Coca-Cola, Pepsi, Fanta, Mirinda, 7Up and Sprite, and two fruit juices were Tropicana orange juice and real orange juice. Ten different bottles from each category were obtained, and the pH was estimated. Each of the beverages was divided into batch of 10 containers containing the tooth sample. Weight of all samples was measured at 24, 48, 72, 96, and 120 hours with subsequently changing each solution at an interval of 24 hours.

Results

The mean pH of the beverages was found ranging from 2.13 ± 0.02 in Pepsi to 3.41 ± 0.02 in Tropicana on opening. The mean pH of water was found to be 6.98 ± 0.01. Among carbonated drinks, the mean weight loss after 24 hours was highest in Coca-Cola and least in 7Up. Tropicana fruit juice had a higher tooth loss than real orange juices. When compared with water, the tooth loss was significantly higher in Coca-Cola after all specified time (hours).

Conclusion

The pH of both carbonated drinks and fruit juices was below the critical pH. The weight loss was also seen after every 24 hours in all the carbonated drinks and beverages. The study showed that these commercial beverages are harmful to the tooth structures, and hence, the health professionals a major role in educating the population about its effects and advising them to use these products precisely.

Clinical significance

The change in lifestyle has increased the demand of soft drinks and artificial juice in Indian market. The use of these carbonated drinks and fruit juices causes damage to the tooth structure in all ages, especially in young mass. Our study provides an idea about the deleterious effects of these commercial drinks on dental hard tissues.

How to cite this article

Panda A, Ghosh B, Pal I, Kumar V, Bhuyan L, Dash KC. Dissolution of Enamel on Exposure to Various Commercial Beverages Available in India. J Contemp Dent Pract 2017;18(11):1009-1013.
Histological Evaluation of the Effect of Platelet-rich Plasma on Pulp Regeneration in Nonvital Open Apex Teeth: An Animal Study
Authors: Forghani Maryam , Jafarzadeh Hamid , Ghoddusi Jamileh , Maghsudlu Amir , Jafarian Amirhossein
Published: November 2017

Aim

Platelet-rich plasma (PRP), which is a concentration of growth factors found in platelets, may be a suitable material for pulp regeneration. The aim of this animal study was a histological evaluation of PRP on pulp regeneration in nonvital teeth with immature apices.

Materials and methods

A total of 40 premolar dogs’ teeth were chosen for this study. After general anesthesia, the teeth were exposed, and subsequently, pulps were removed and the cavities were opened to the oral cavity. After 2 weeks, root canals were irrigated and disinfected with sodium hypochlorite with noninstrumentation technique, and triple antibiotic paste was placed inside the canals. Cavities were sealed with a temporary restoration. About 4 weeks later, canals were irrigated again and the teeth were randomly divided into three groups. Bleeding was evoked with overinstrumentation, then experimental materials for each group [PRP, mineral trioxide aggregate (MTA), and parafilm respectively] were placed over the bleeding, and orifices were sealed with MTA and glass ionomer. After 3 months, dogs were sacrificed and the teeth were separated from the jaws and sections prepared for histological evaluation.

Results

Regeneration was shown in 44.7% of the samples. About 47.3% of the samples in the MTA group and 42.1% of the samples in the PRP group showed regeneration; however, no regeneration was observed in the parafilm group. Chi-square test showed no significant difference between groups I and II. The soft regenerative tissue included pulp-like tissue and vessels. Mineralized regenerative tissue included cementumlike, periodontal ligament-like, and bone-like tissues. No normal pulp and nerve tissue were observed.

Conclusion

Both PRP and MTA may be ideal scaffolds to accelerate the regeneration process.

Clinical significance

Pulp repair in immature permanent teeth with weak roots has a better outcome than replacement of the pulp with gutta-percha or biomaterials.

How to cite this article

Ghoddusi J, Maghsudlu A, Jafarzadeh H, Jafarian A, Forghani M. Histological Evaluation of the Effect of Platelet-rich Plasma on Pulp Regeneration in Nonvital Open Apex Teeth: An Animal Study. J Contemp Dent Pract 2017;18(11):1045-1050.