Dual-Specificity Phosphatases: A sub-class of protein tyrosine phosphatases that contain an additional phosphatase activity which cleaves phosphate ester bonds on SERINE or THREONINE residues that are located on the same protein.MicroRNAs: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.Streptomyces griseus: An actinomycete from which the antibiotics STREPTOMYCIN, grisein, and CANDICIDIN are obtained.3' Untranslated Regions: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.Protein Tyrosine Phosphatases: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.Insectivora: An order of insect eating MAMMALS including MOLES; SHREWS; HEDGEHOGS and tenrecs.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.PTEN Phosphohydrolase: A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Adenylosuccinate Synthase: A carbon-nitrogen ligase. During purine ribonucleotide biosynthesis, this enzyme catalyzes the synthesis of adenylosuccinate from GTP; IMP; and aspartate with the formation of orthophosphate and GDP. EC 6.3.4.4.Adenylosuccinate Lyase: An enzyme that, in the course of purine ribonucleotide biosynthesis, catalyzes the conversion of 5'-phosphoribosyl-4-(N-succinocarboxamide)-5-aminoimidazole to 5'-phosphoribosyl-4-carboxamide-5-aminoimidazole and the conversion of adenylosuccinic acid to AMP. EC 4.3.2.2.Purine Nucleotides: Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Inosine Monophosphate: Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Hydroxymethyl and Formyl Transferases: Enzymes that catalyze the transfer of hydroxymethyl or formyl groups. EC 2.1.2.Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.Amidophosphoribosyltransferase: An enzyme, involved in the early steps of purine nucleotide biosynthesis, that catalyzes the formation of 5-phosphoribosylamine from glutamine and phosphoribosylpyrophosphate. EC 2.4.2.14.Phosphoribosylaminoimidazolecarboxamide Formyltransferase: An enzyme that catalyzes the conversion of aminoimidazole-4-carboxamide ribonucleotide to 5-formyl-aminoimidazole-4-carboxamide ribonucleotide in the purine de novo synthesis pathway. It requires the cofactor N(10)-FORMYLTETRAHYDROFOLATE as the formyl donor.Haemophilus influenzae: A species of HAEMOPHILUS found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII.Haemophilus Infections: Infections with bacteria of the genus HAEMOPHILUS.Haemophilus: A genus of PASTEURELLACEAE that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile.Metabolome: The dynamic collection of metabolites which represent a cell's or organism's net metabolic response to current conditions.Metabolomics: The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions.Inosine NucleotidesPoly I: A group of inosine ribonucleotides in which the phosphate residues of each inosine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.Purine-Pyrimidine Metabolism, Inborn ErrorsHypoxanthines: Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.Inosine: A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)Poly I-C: Interferon inducer consisting of a synthetic, mismatched double-stranded RNA. The polymer is made of one strand each of polyinosinic acid and polycytidylic acid.DNA, Single-Stranded: A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.Societies, Pharmaceutical: Societies whose membership is limited to pharmacists.Simbu virus: A species in the ORTHOBUNYAVIRUS genus of the family BUNYAVIRIDAE family. Previously a large group of serotypes, most are now considered separate species.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Methylurea Compounds: Urea compounds which are substituted with one or more methyl groups.Silk: A continuous protein fiber consisting primarily of FIBROINS. It is synthesized by a variety of INSECTS and ARACHNIDS.Spiders: Arthropods of the class ARACHNIDA, order Araneae. Except for mites and ticks, spiders constitute the largest order of arachnids, with approximately 37,000 species having been described. The majority of spiders are harmless, although some species can be regarded as moderately harmful since their bites can lead to quite severe local symptoms. (From Barnes, Invertebrate Zoology, 5th ed, p508; Smith, Insects and Other Arthropods of Medical Importance, 1973, pp424-430)Information Storage and Retrieval: Organized activities related to the storage, location, search, and retrieval of information.Calcium Compounds: Inorganic compounds that contain calcium as an integral part of the molecule.Enzootic Bovine Leukosis: A lymphoid neoplastic disease in cattle caused by the bovine leukemia virus. Enzootic bovine leukosis may take the form of lymphosarcoma, malignant lymphoma, or leukemia but the presence of malignant cells in the blood is not a consistent finding.Bunyaviridae Infections: Virus diseases caused by the BUNYAVIRIDAE.
(1/71) Combinatorial interactions regulate cardiac expression of the murine adenylosuccinate synthetase 1 gene.

The mammalian heart begins contracting at the linear tube stage during embryogenesis and continuously pumps, nonstop, throughout the entire lifetime of the animal. Therefore, the cardiac energy metabolizing pathways must be properly established and efficiently functioning. While the biochemistry of these pathways is well defined, limited information regarding the regulation of cardiac metabolic genes is available. Previously, we reported that 1.9 kilobase pairs of murine adenylosuccinate synthetase 1 gene (Adss1) 5'-flanking DNA directs high levels of reporter expression to the adult transgenic heart. In this report, we define the 1.9-kilobase pair fragment as a cardiac-specific enhancer that controls correct spatiotemporal expression of a reporter similar to the endogenous Adss1 gene. A 700-base pair fragment within this region activates a heterologous promoter specifically in adult transgenic hearts. Proteins present in a cardiac nuclear extract interact with potential transcription factor binding sites of this region and these cis-acting sites play important regulatory roles in the cardiac expression of this reporter. Finally, we report that several different cardiac transcription factors trans-activate the 1.9HSCAT construct through these sites and that combinations result in enhanced reporter expression. Adss1 appears to be one of the first target genes identified for the bHLH factors Hand1 and Hand2.  (+info)

(2/71) Effectors of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase.

Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a pleiotropic effector of the stringent response, potently inhibits adenylosuccinate synthetase from Escherichia coli as an allosteric effector and/or as a competitive inhibitor with respect to GTP. Crystals of the synthetase grown in the presence of IMP, hadacidin, NO3-, and Mg2+, then soaked with ppGpp, reveal electron density at the GTP pocket which is consistent with guanosine 5'-diphosphate 2':3'-cyclic monophosphate. Unlike ligand complexes of the synthetase involving IMP and GDP, the coordination of Mg2+ in this complex is octahedral with the side chain of Asp13 in the inner sphere of the cation. The cyclic phosphoryl group interacts directly with the side chain of Lys49 and indirectly through bridging water molecules with the side chains of Asn295 and Arg305. The synthetase either directly facilitates the formation of the cyclic nucleotide or scavenges trace amounts of the cyclic nucleotide from solution. Regardless of its mode of generation, the cyclic nucleotide binds far more tightly to the active site than does ppGpp. Conceivably, synthetase activity in vivo during the stringent response may be sensitive to the relative concentrations of several effectors, which together exercise precise control over the de novo synthesis of AMP.  (+info)

(3/71) Adenylosuccinate synthase from Saccharomyces cerevisiae: homologous overexpression, purification and characterization of the recombinant protein.

Adenylosuccinate synthase (EC 6.3.4.4) catalyses the first committed step in the synthesis of adenosine. We have overexpressed the cloned gene of Saccharomyces cerevisiae (ADE12) in S. cerevisiae. The recombinant enzyme exhibits similar kinetic behaviour to that of the native enzyme purified from S. cerevisiae. This ter-reactant dimeric enzyme shows Michaelis-Menten kinetics only with IMP. l-Aspartate and GTP display a weak negative co-operativity (Hill coefficient 0. 8-0.9). This negative co-operativity has not yet been reported for adenylosuccinate synthases from other organisms. Another unusual feature of the enzyme from S. cerevisiae is its negligible inhibition by adenine nucleotides and its pronounced inhibition by Cl(-) ions.  (+info)

(4/71) Electrical stimulation of neonatal cardiac myocytes activates the NFAT3 and GATA4 pathways and up-regulates the adenylosuccinate synthetase 1 gene.

Electrically stimulated pacing of cultured cardiomyocytes serves as an experimentally convenient and physiologically relevant in vitro model of cardiac hypertrophy. Electrical pacing triggers a signaling cascade that results in the activation of the muscle-specific Adss1 gene and the repression of the nonmuscle Adss2 isoform. Activation of the Adss1 gene involves the calcineurin-mediated dephosphorylation of NFAT3, allowing its translocation to the nucleus, where it can directly participate in Adss1 gene activation. Mutational studies show that an NFAT binding site located in the Adss1 5'-flanking region is essential for this activation. Electrical pacing also results in the increased synthesis of GATA4, another critical cardiac transcription factor required for Adss1 gene expression. MEF2C also produces transactivation of the Adss1 gene reporter in control and paced cardiac myocytes. Using the Adss1 gene as a model, these studies are the first to demonstrate that electrical pacing activates the calcineurin/NFAT3 and GATA4 pathways as a means of regulating cardiac gene expression.  (+info)

(5/71) Investigation of various genotype characteristics for inosine accumulation in Escherichia coli W3110.

For the derivation of an inosine-overproducing strain from the wild type microorganism, it is known that the addition of an adenine requirement, removal of purine nucleoside hydrolyzing activity, removal of the feedback inhibition, and repression of key enzymes in the purine nucleotides biosynthetic pathway are essential. Thus, the disruption of purA (adenine requirement), deoD (removal of purine nucleosides phosphorylase activity), purR (derepression of the regulation of purine nucleotides biosynthetic pathway), and the insensitivity of the feedback inhibition of phosphoribosylpyrophosphate (PRPP) amidotransferase by adenosine 5'-monophosphate (AMP) and guanosine 5'-monophosphate (GMP) were done in the Escherichia coli strain W3110, and then the inosine productivity was estimated. In the case of using a plasmid harboring the PRPP amidotransferase gene (purF) that encoded a desensitized PRPP amidotransferase, purF disrupted mutants were used as the host strains. It was found that the innovation of the four genotypes brought about a small amount of inosine accumulation. Furthermore, an adenine auxotrophic mutant of E. coli showed inappropriate adenine use because its growth could not respond efficiently to the concentration of adenine added. As the presence of adenosine deaminase is well known in E. coli and it is thought to be involved in adenine use, a mutant disrupted adenosine deaminase gene (add) was constructed and tested. The mutant, which is deficient in purF, purA, deoD, purR, and add genes, and harboring the desensitized purF as a plasmid, accumulated about 1 g of inosine per liter. Although we investigated the effects of purR disruption and purF gene improvement, unexpectedly an increase in the inosine productivity could not be found with this mutant.  (+info)

(6/71) Recombinant mouse muscle adenylosuccinate synthetase: overexpression, kinetics, and crystal structure.

Vertebrates possess two isozymes of adenylosuccinate synthetase. The acidic isozyme is similar to the synthetase from bacteria and plants, being involved in the de novo biosynthesis of AMP, whereas the basic isozyme participates in the purine nucleotide cycle. Reported here is the first instance of overexpression and crystal structure determination of a basic isozyme of adenylosuccinate synthetase. The recombinant mouse muscle enzyme purified to homogeneity in milligram quantities exhibits a specific activity comparable with that of the rat muscle enzyme isolated from tissue and K(m) parameters for GTP, IMP, and l-aspartate (12, 45, and 140 microm, respectively) similar to those of the enzyme from Escherichia coli. The mouse muscle and E. coli enzymes have similar polypeptide folds, differing primarily in the conformation of loops, involved in substrate recognition and stabilization of the transition state. Residues 65-68 of the muscle isozyme adopt a conformation not observed in any previous synthetase structure. In its new conformation, segment 65-68 forms intramolecular hydrogen bonds with residues essential for the recognition of IMP and, in fact, sterically excludes IMP from the active site. Observed differences in ligand recognition among adenylosuccinate synthetases may be due in part to conformational variations in the IMP pocket of the ligand-free enzymes.  (+info)

(7/71) IMP Alone Organizes the Active Site of Adenylosuccinate Synthetase from Escherichia coli.

A complete set of substrate/substrate analogs of adenylosuccinate synthetase from Escherichia coli induces dimer formation and a transition from a disordered to an ordered active site. The most striking of the ligand-induced effects is the movement of loop 40-53 by up to 9 A. Crystal structures of the partially ligated synthetase, which either combine IMP and hadacidin or IMP, hadacidin, and Mg(2+)-pyrophosphate, have ordered active sites, comparable with the fully ligated enzyme. More significantly, a crystal structure of the synthetase with IMP alone exhibits a largely ordered active site, which includes the 9 A movement of loop 40-53 but does not include conformational adjustments to backbone carbonyl 40 (Mg(2+) interaction element) and loop 298-304 (L-aspartate binding element). Interactions involving the 5'-phosphoryl group of IMP evidently trigger the formation of salt links some 30 A away. The above provides a structural basis for ligand binding synergism, effects on k(cat) due to mutations far from the site of catalysis, and the complete loss of substrate efficacy due to minor alterations of the 5'-phosphoryl group of IMP.  (+info)

(8/71) Determinants of L-aspartate and IMP recognition in Escherichia coli adenylosuccinate synthetase.

Adenylosuccinate synthetase governs the first committed step in the de novo synthesis of AMP. Mutations of conserved residues in the synthetase from Escherichia coli reveal significant roles for Val(273) and Thr(300) in the recognition of l-aspartate, even though these residues do not or cannot hydrogen bond with the substrate. The mutation of Thr(300) to alanine increases the K(m) for l-aspartate by 30-fold. In contrast, its mutation to valine causes no more than a 4-fold increase in the K(m) for l-aspartate, while increasing k(cat) by 3-fold. Mutations of Val(273) to alanine, threonine, or asparagine increase the K(m) for l-aspartate from 15- to 40-fold, and concomitantly decrease the K(i) for dicarboxylate analogues of l-aspartate by up to 40-fold. The above perturbations are comparable with those resulting from the elimination of a hydrogen bond between the enzyme and substrate: alanine mutations of Thr(128) and Thr(129) increase the K(m) for IMP by up to 30-fold and the alanine mutation of Thr(301) abolishes catalysis supported by l-aspartate, but has no effect on catalysis supported by hydroxylamine. Structure-based mechanisms, by which the above residues influence substrate recognition, are presented.  (+info)

*  Adenylosuccinate synthase
Humans express two adenylosuccinate synthase isozymes: Adenylosuccinate synthase at the US National Library of Medicine Medical ... In molecular biology, Adenylosuccinate synthase (or adenylosuccinate synthetase) (EC 6.3.4.4.) is an enzyme that plays an ... Adenylosuccinate synthetase has been characterised from various sources ranging from Escherichia coli (gene purA) to vertebrate ... Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known ...
*  Nucleotide
First, GTP hydrolysis fuels the addition of aspartate to IMP by adenylosuccinate synthase, substituting the carbonyl oxygen for ... This step is catalyzed by adenylosuccinate lyase. Inosine monophosphate is converted to guanosine monophosphate by the ... a nitrogen and forming the intermediate adenylosuccinate. Fumarate is then cleaved off forming adenosine monophosphate. ...
*  Adenylosuccinate
The enzyme adenylosuccinate synthase carries out the reaction by the addition of aspartate to IMP and requires the input of ... Adenylosuccinate lyase deficiency Purine nucleotide cycle Figures 20.4 and 20.7 in Textbook of Biochemistry, with clinical ... Adenylosuccinate is an intermediate in the interconversion of purine nucleotides inosine monophosphate (IMP) and adenosine ...
*  Purine metabolism
GMP back into IMP adenylosuccinate synthase converts IMP to adenylosuccinate adenylosuccinate lyase converts adenylosuccinate ... AICAR + fTHF → FAICAR + THF The last step is catalyzed by Inosine monophosphate synthase. FAICAR → IMP + H2O In eukaryotes the ... CAIR + L-Aspartate + ATP → SAICAR + ADP + Pi The eight is catalyzed by adenylosuccinate lyase. SAICAR → AICAR + Fumarate The ... IMP dehydrogenase (IMPDH) converts IMP into XMP GMP synthase converts XMP into GMP GMP reductase converts ...
*  List of MeSH codes (D08)
... adenylosuccinate synthase MeSH D08.811.464.259.200 --- amide synthases MeSH D08.811.464.259.200.200 --- aspartate-ammonia ... riboflavin synthase MeSH D08.811.913.225.825 --- spermidine synthase MeSH D08.811.913.225.912 --- spermine synthase MeSH ... nitric oxide synthase type i MeSH D08.811.682.664.500.772.500 --- nitric oxide synthase type ii MeSH D08.811.682.664.500.772. ... glycogen synthase kinases MeSH D08.811.913.696.620.682.700.429.500 --- glycogen synthase kinase 3 MeSH D08.811.913.696.620.682. ...
*  List of EC numbers (EC 6)
... adenylosuccinate synthase EC 6.3.4.5: argininosuccinate synthase EC 6.3.4.6: urea carboxylase EC 6.3.4.7: ribose-5-phosphate- ... arginine b-lactam-synthase EC 6.3.4.1: GMP synthase. Now included in EC 6.3.5.2, GMP synthase (glutamine-hydrolysing). EC 6.3. ... imidazole ribonucleotide synthase EC 6.3.4.19: tRNAIle-lysidine synthase EC 6.3.4.20: 7-cyano-7-deazaguanine synthase EC 6.3. ... glutathionylspermidine synthase EC 6.3.1.9: trypanothione synthase EC 6.3.1.10: adenosylcobinamide-phosphate synthase EC 6.3. ...
*  Morpheein
An example of such a conformational disease is ALAD porphyria, which results from a mutation of porphobilinogen synthase that ... Palenchar, Jennifer Brosius; Colman, Roberta F. (2003). "Characterization of a Mutant Bacillus subtilis Adenylosuccinate Lyase ... The one protein that is established to function as a morpheein is porphobilinogen synthase, though there are suggestions ... An inhibitor of porphobilinogen synthase with this mechanism of action has been documented. The morpheein model of allosteric ...
*  List of EC numbers (EC 4)
11-diene synthase EC 4.2.3.25: S-linalool synthase EC 4.2.3.26: R-linalool synthase EC 4.2.3.27: isoprene synthase EC 4.2.3.28 ... adenylosuccinate lyase EC 4.3.2.3: ureidoglycolate lyase EC 4.3.2.4: purine imidazole-ring cyclase EC 4.3.2.5: ... d-cadinene synthase EC 4.2.3.14: pinene synthase EC 4.2.3.15: myrcene synthase EC 4.2.3.16: (4S)-limonene synthase EC 4.2.3.17 ... chorismate synthase EC 4.2.3.6: trichodiene synthase EC 4.2.3.7: pentalenene synthase EC 4.2.3.8: casbene synthase EC 4.2.3.9: ...
Shop Probable rhodanese domain-containing dual specificity protein phosphatase ELISA Kit, Recombinant Protein and Probable rhodanese domain-containing dual specificity protein phosphatase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Looking for online definition of dual-specificity phosphatase MKP-5 in the Medical Dictionary? dual-specificity phosphatase MKP-5 explanation free. What is dual-specificity phosphatase MKP-5? Meaning of dual-specificity phosphatase MKP-5 medical term. What does dual-specificity phosphatase MKP-5 mean?
Dual specificity protein phosphatase; active with phosphotyrosine, phosphoserine and phosphothreonine residues. The highest relative activity is toward ERK1.
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Lafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). In the present study, we demonstrate that laforin is a phosphoprotein, as indicated by two-dimensional electrophoresis, and we identify Ser25 as the residue involved in this modification. We also show that Ser25 is phosphorylated both in vitro and in vivo by AMPK. Lastly, we demonstrate that this residue plays a critical role for both the phosphatase activity and the ability of laforin to interact with itself and with previously established binding ...
The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas, and unlike most other members of this family, is localized in the cytoplasm. Two transcript variants encoding different isoforms have been found for this gene ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Protein homeostasis or proteostasis is a fundamental cellular property that encompasses the dynamic balancing of processes in the proteostasis network (PN). Such processes include protein synthesis, folding, and degradation in both non-stressed and stressful conditions. The role of the PN in neurodegenerative disease is well-documented, where it is known to respond to changes in protein folding states or toxic gain-of-function protein aggregation. Dual-specificity phosphatases have recently emerged as important participants in maintaining balance within the PN, acting through modulation of cellular signaling pathways that are involved in neurodegeneration. In this review, we will summarize recent findings describing the roles of dual-specificity phosphatases in neurodegeneration and offer perspectives on future therapeutic directions.
DUSP27 dual specificity phosphatase 27 Proteins available through Novus Biologicals. Browse our DUSP27 dual specificity phosphatase 27 Protein catalog backed by our Guarantee+.
Mutations in Lafora disease genes (laforin and malin) and in Univerricht-Lundborg PME genes (cystatin B) are inherited in an autosomal recessive fashion. The gene EPM2A makes an enzyme called dual specificity protein phosphatase or laforin, and the gene EPM2B makes another enzyme named ubiquitin E3 ligase or malin. Therefore, most cases of Lafora PMEs are enzymopathies, are classified as lysosomal diseases, and produce a system-wide glycogen storage disorder. A minority of cases of Lafora disease are caused by as yet unidentified genes. Cystatin B is a cysteine protease inhibitor and its deficiency causes abnormal activation of cathepsin S. G1qB-chain of complement, beta2-microglubulin, glial fibrillary acidic protein, apolipoprotein D, fibronectin 1, and metallothionein II, which are factors involved in proteolysis, apoptosis, and glial activation (Leiuallen et al., 2001). The lysosome-associated functions of cystatin B are also associated with the pathogenic mutations, suggesting that ...
Sustained activation of extracellular signal-regulated kinase (ERK) has been detected previously in numerous tumors in the absence of RAS-activating mutations. However, the molecular mechanisms responsible for ERK-unrestrained activity independent of RAS mutations remain unknown. Here, we evaluated the effects of the functional interactions of ERK proteins with dual-specificity phosphatase 1 (DUSP1), a specific inhibitor of ERK, and S-phase kinase-associated protein 2 (SKP2)/CDC28 protein kinase 1b (CKS1) ubiquitin ligase complex in human hepatocellular carcinoma (HCC). Levels of DUSP1, as assessed by real-time reverse transcription-PCR and Western blot analysis, were significantly higher in tumors with better prognosis (as defined by the length of patients survival) when compared with both normal and nontumorous surrounding livers, whereas DUSP1 protein expression sharply declined in all HCC with poorer prognosis. In the latter HCC subtype, DUSP1 inactivation was due to either ...
High Unmet Need for this Rare and Fatal Form of Epilepsy -. - Planning Underway for Initiation of Clinical Studies in Lafora Patients -. CONCORD, Mass., Sept. 6, 2017 /PRNewswire/ - Valerion Therapeutics, a clinical-stage biotechnology company that specializes in the development of therapies for orphan genetic diseases, today announced preclinical proof-of-concept results providing early validation of VAL-0417 as a potential treatment for Lafora disease, a rare and fatal genetic form of epilepsy, characterized by an accumulation of aberrant glycogen-containing deposits known as Lafora bodies. VAL-0417 is a novel fusion protein that combines Valerions delivery antibody (3E10) linked to amylase, to uniquely target Lafora bodies present in all tissues of Lafora disease patients. Data from this study were presented at the 2017 Lafora Disease Workshop, a satellite symposium of the 32nd International Epilepsy Congress being held September 2-6, 2017 in Barcelona, Spain.. "Current treatments for Lafora ...
DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages, and that its deficiency in mice promotes tolerance to LPS-induced endotoxin shock and to polymicrobial septic shock after cecal ligation and puncture. By using adoptive transfer experiments, we demonstrate that resistance to endotoxin is macrophage dependent and transferable, and that this protection is associated with a striking increase of M2-like macrophages in DUSP3−/− mice in both the LPS and cecal ligation and puncture models. We show that the altered response of DUSP3−/− mice to sepsis is reflected in decreased TNF production and impaired ERK1/2 activation. Our results demonstrate that DUSP3 plays a key and nonredundant role as a regulator of innate immune responses by mechanisms involving the control of ERK1/2 activation, TNF secretion, and macrophage polarization. ...
An example of a metabolic disease caused by defective enzymes is Lafora disease. Lafora disease, named after Dr. Gonzalo Lafora, is a metabolic disorder that is caused by defective enzymes that controls phosphorylation. It is a neurodegenerative disease caused by insoluble glucan accumulating in the cytoplasm. Glucan is a type of complex carbohydrate that is made up of glucose linked together by glycosidic bonds. Lafora disease not only causes epilepsy, but also progressive central nervous system degenerations. This ultimately results in the death of the patient. It is thought that the compilation of cytoplasmic lipid bodies (LB) trigger neuronal cell death and seizures.. It is recognized that in almost half of Lafora disease cases, the EPM2A (epilepsy, progressive myoclonus 2A) gene is mutated. The EPM2A gene encodes the bimodular protein called laforin. Laforin is associated with regulating glycogen metabolism. Glycogen stores long-term energy. Furthermore, about 20% if Lafora disease cases ...
By reversing the phosphorylation of key regulatory proteins mediated by protein kinases, phosphatases serve as an important complement to kinases and attenuate activated signal transduction pathways. Important classes of phosphatases include both receptor and nonreceptor protein tyrosine phosphatases (PTPs), dual specificity phosphatases (DUSPs), cell cycle regulatory phosphatases, the 4 major serine/threonine protein phosphatase gene families (PP1, PP2A, PP2B, and PP2C), and other increasingly important gene families (PP4, PP5, PP6, and PP7). PTPs regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. DUSPs can dephosphorylate serine and threonine as well as tyrosine residues, primarily targeting MAP kinases. PP1 family members regulate of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. PP2A family members negatively regulate ...
Cell. 1993 Nov 5;75(3):487-93. Research Support, Non-U.S. Govt; Research Support, U.S. Govt, Non-P.H.S.; Research Support, U.S. Govt, P.H.S.
A collection of disease information resources and questions answered by our Genetic and Rare Diseases Information Specialists for Lafora disease
Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is a nuclear, dual-specificity phosphatase that has been shown to dephosphorylate MAP kinases. We used a substrate-trap technique involving a mutation in MKP-1 of the catalytically critical cysteine to a serine residue (CS mutant) to capture novel MKP-1 substrates. We transfected the MKP-1 (CS) mutant and control (wild-type, WT) constructs into phorbol 12-myristate 13-acetate (PMA)-activated COS-1 cells. MKP-1-substrate complexes were immunoprecipitated, which yielded four bands of 17, 15, 14, and 10 kDa with the CS MKP-1 mutant but not the WT MKP-1. The bands were identified by mass spectrometry as histones H3, H2B, H2A, and H4, respectively. Histone H3 was phosphorylated, and purified MKP-1 dephosphorylated histone H3 (phospho-Ser-10) in vitro; whereas, histone H3 (phospho-Thr-3) was unaffected. We have previously shown that thrombin and vascular endothelial growth factor (VEGF) upregulated MKP-1 in human endothelial cells (EC). We now
Muscle biopsy specimens from two patients with progressive myoclonus epilepsy (Lafora type) showed a prominent stippling pattern in muscle fibers with the nicot
Title: Impact of Oncogenic Protein Tyrosine Phosphatases in Cancer. VOLUME: 12 ISSUE: 1. Author(s):Serge Hardy, Sofi G. Julien and Michel L. Tremblay. Affiliation:McGill University, Goodman Cancer Centre 1160 Pine Avenue, Room 601 Montreal, QC, Canada H3A 1A3.. Keywords:Cancer, Inhibitors, dual-specificity phosphatases (DSPs), Oncogene, Protein tyrosine phosphatases, Phosphorylation, Tumor suppressor, G protein-coupled receptors (GPCRs), Amplification, Gynecological Cancers. Abstract: Protein tyrosine phosphatases (PTPs) constitute a large family of enzymes that can exert both positive and negative effects on signaling pathways. They play dominant roles in setting the levels of intracellular phosphorylation downstream of many receptors including receptor tyrosine kinases and G protein-coupled receptors. As observed with kinases, deregulation of PTP activity can also contribute to cancer. This review will examine a broad array of PTP family members that positively affect oncogenesis in human ...
Phosphoprotein phosphatases, which hydrolyze the phosphoester bonds of phosphoserines, phosphothreonines or phosphotyrosines, play an essential role in signal transduction and actively contribute to the regulation of protein phosphorylation. On the basis of their substrate specificity they are usually divided into phosphoserine and phosphothreonine phosphatases on the one hand, and phosphotyrosine and dual-specificity phosphatases, on the other hand. This division corresponds also to different families of enzymes with different catalytic mechanisms. Genes coding for phosphoserine/threonine phosphatases are less numerous in vertebrate genomes than those for serine /threonine kinases, and the complexity of phosphatases function arises in part from the interactions of catalytic subunits with other proteins.. Prior to the knowledge of their sequence, phosphoserine/threonine phosphatases were classified on the basis of their substrate preference and inhibitor sensitivity. Type 1 protein phosphatases ...
Constitutively active Ras negatively regulates Erk MAP kinase through induction of MAP kinase phosphatase 3 (MKP3) in NIH3T3 cells;kpubs;kpubs.org
NIH Rare Diseases : 50 polyglucosan body disease affects the nervous system. individuals with this condition usually begin to show signs of the disorder after the age of 40. signs and symptoms include trouble walking due to decreased sensation in the legs (peripheral neuropathy) and muscle weakness and stiffness (spasticity). individuals may also have trouble controlling bladder function as a result of damage to the nerves of the bladder (neurogenic bladder). approximately half of the individuals with adult polyglucosan body disease also experience some degree of intellectual impairment. mutations in the gbe1 gene can cause adult polyglucosan body disease. in some cases, no mutation can be found and the cause of the disease is not known. adult polyglucosan body disease is thought to be inherited in an autosomal recessive manner. treatment usually involves a team of specialists who can address the specific symptoms such as walking difficulties, incontinence, and intellectual impairment. last ...
Abbreviations: BLMEC, bovine lung microvascular endothelial cell; DUSP, dual-specificity phosphatase; E, embryonic day; eNOS, endothelial nitric oxide synthase; ERK, extracellular-signal-regulated kinase; FGF2, fibroblast growth factor 2; HDMEC, human dermal microvascular endothelial cell; HUVEC, human umbilical vein endothelial cell; KLF, Krüppel-like factor; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEF, myocyte enhancer factor; MEK, MAPK/ERK kinase; MEKK, MEK kinase; MKP, MAPK phosphatase; NF-κB, nuclear factor κB; NLS, nuclear localization signal; NRF2, nuclear erythroid 2-related factor 2; PKB, protein kinase B; RSK, ribosomal S6 kinase; SGK, serum- and glucocorticoid-regulated protein kinase; TNFα, tumour necrosis factor α; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor ...
Innate immune responses mediated by Toll-like receptors (TLRs), a class of pattern-recognition receptors, play a critical role in the defense against microbial pathogens. However, excessive TLR-mediated responses result in sepsis, autoimmunity, and chronic inflammation. To prevent deleterious activation of TLRs, cells have evolved multiple mechanisms that inhibit innate immune reactions. Stimulation of TLRs induces the expression of the gene encoding the mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a nuclear-localized dual-specificity phosphatase that preferentially dephosphorylates p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in the attenuation of TLR-triggered production of proinflammatory cytokines. MKP-1 is posttranslationally modified by multiple mechanisms, including phosphorylation. A study now demonstrates that MKP-1 is also acetylated on a key lysine residue following stimulation of TLRs. Acetylation of MKP-1 promotes the interaction of MKP-1 with its ...
in Circulation (2015), 131(7), 656-68. Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet ... [more ▼]. Background A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function. Methods and Results This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) ...
BioAssay record AID 743310 submitted by Burnham Center for Chemical Genomics: SAR confirmation of uHTS small molecule inhibitors of Low Molecular Weight Protein Tyrosine Phosphatase, LMPTP, in a fluorescence-based, VHR-1 (dual specificity phosphatase 3) selectivity assay.
Cellularization is coordinated with a dramatic increase in inhibitory phosphorylation of the mitotic Cdc2 kinase (Edgar et al., 1994). The grp mutation blocks the increase in Cdc2 phosphorylation that normally accompanies interphase 14 and cellularization, and the Chk1 encoded by grp inhibits Cdc25, a dual specificity phosphatase that activates Cdc2 by reversing this modification (Walworth, 2001). These findings suggest that Chk1 activation leads to increases in Cdc2 phosphorylation during interphase 14, and that this modification may be essential to cellularization (Sibon et al., 1997). We therefore assayed mnk grp double-mutant embryos, which lack Chk1, for Cdc2 phosphorylation. As shown in Fig. 2C, Cdc2 phosphorylation is restored in mnk grp mutants, indicating that this process does not require Chk1 or a functional replication checkpoint. Maternal Cdc25 mRNA and protein, which are encoded by string and twine, are normally degraded early in interphase 14, and these processes require zygotic ...
Dysregulation of cell cycle machinery is implicated in a number of neuronal death contexts, including stroke. Increasing evidence suggests that cyclin-dependent kinases (Cdks) are inappropriately activated in mature neurons under ischemic stress conditions. We previously demonstrated a functional role for cyclin D1/Cdk4/pRb pathway in delayed neuronal death induced by ischemia. However, the molecular signal(s) leading to cyclin D/Cdk4/pRb activation following ischemic insult is presently not clear. Here, we investigate the cell division cycle 25 (Cdc25) dual specificity phosphatases as potential upstream regulators of ischemic neuronal death and Cdk4 activation. We show that a pharmacologic inhibitor of Cdc25 family members (A, B & C) protects mouse primary neurons from hypoxia-induced delayed death. The major contributor to the death process appears to be Cdc25A. shRNA mediated knockdown of Cdc25A protects neurons in a delayed model of hypoxia-induced death in vitro. Similar results were ...
By Vice President for Research Lisa Cassis Thursday. In May, it was my distinct pleasure to present Matthew Gentry with a University Research Professorship award. He was one of 16 faculty, selected by their own colleges, who have demonstrated excellence in scholarship and creative work that addresses scientific, social, cultural and economic challenges in our region and around the world.. Gentry, a professor of molecular and cellular biochemistry in the College of Medicine, has received an NSF Faculty Career Development Award, NIH Pathway to Independence Award, three U.S. patents, and a five-year, $8.5 million NIH grant to pursue a cure for Lafora disease, a deadly congenital form of epilepsy.. His research began with a plant protein that controls the production of biofuels. It turns out mutations in a similar protein in humans result in Lafora disease. He explains, "The discoveries that we made in the plant system were directly applicable to the human system, and that led us down this road now ...
We next addressed the question of whether Pmp1 modulated the level of Pmk1 tyrosine phosphorylation in vivo. As shown in Figure 8B, Pmk1 tyrosine phosphorylation was significantly enhanced in Δpmp1 cells, but almost completely abolished in cells overproducing Pmp1. In sharp contrast, overproduction of catalytically inactive Pmp1C158S resulted in an elevated level of tyrosine‐phosphorylated Pmk1 (Figure 8B).. With the goal of establishing that Pmk1 MAP kinase is a direct target of Pmp1 phosphatase in vivo, we then asked whether Pmp1 and Pmk1 physically interacted. For this, hemagglutinin (HA) epitope‐tagged Pmk1 and GST-Pmp1, GST-Pmp1C158S or unfused GST were co‐expressed in S.pombe, followed by precipitation with glutathione beads. Beads were washed thoroughly and analyzed by immunoblotting using anti‐HA and anti‐GST antibodies. The results obtained (Figure 8C) clearly show that HA‐tagged Pmk1 co‐precipitates with GST-Pmp1, but not with unfused GST. A much larger amount of Pmk1 ...
With the authors permission, heres a particularly insightful post to a DSPS support group. Thanks, V., for letting me use this! _ _ _ _ Its interesting to me when someone comes on and talks about a cure to see the reaction. I think theres way more to this than just…
A GENDA Welcome and Overview of Presentation Whats New in the DSPS FY EOY Expenditures Report Completing the EOY Expenditure Report Demonstration - All Review of Part I-III Review of Part IV-V Q/A & Wrap up
DSPS is where you fall asleep at an inconvenient time and can interfere with your work life and prospects. Sleep pattern out of control? Are you always tired? Get all the answers you need right here
No kind of sex is like an algea test: you cant just start in classroom 203 when the bell goes off and go through the motions to get a passing grade and expect it Here are 50 interesting facts about this award-winning singer. Ed Sheeran Yellow Pages Chords Health lafora disease is a rare genetic disorder marked by the presence of abnormal polyglucosan deposits. Stress getting your erection down? September 1 2013 by Dr Elaine Ryan Leave a Comment. Statin therapy may help prevent erectile dysfunction? Phosphodiesterase inhibitors are drugs or sustances that act on one of the five subtypes of the Ed Balls a former Secretary of State Celeity Bake Off runner-up and current chair treatment to cure impotence yeast red rice of Norwich City FC was rehearsing for Strictly Come Dancing on Saturday as news Ed Sheeran Yellow Pages Chords Health erectile dysfunction pills cheap A recent report from Episodul circula pe internet si este Povestea Episodului Pierdut din Ed Edd si Eddy A woman talks about the ...
Abstract Monocytic adhesion and chemotaxis are regulated by MAPK pathways, which in turn are controlled by redox-sensitive MAPK phosphatases (MKPs). We recently reported that metab..
100158317(ptpn18.S) 100158454(cdc25b.L) 100158455(cdc25b.S) 100337563(cdc25c1) 100380954(ptpn6.L) 100381158(dusp11.L) 100505429 100505440(pten.S) 108695247 108695338 108695998(dusp5.L) 108696044 108696116 108696129 108696416(ubash3b.L) 108696762(ptprh.L) 108697240 108697335(ptpn6.S) 108697391 108697403 108697609(ubash3b.S) 108697805(ptprh.S) 108698701(ptpn21.L) 108700485(ptpn21.S) 108700608 108700974 108701259(ptpn4.L) 108701650(pgp.L) 108701771 108702275(dusp19.S) 108702431 108702587 108702596(ptpn1.S) 108702754 108702927 108703346(dusp13.S) 108703376 108704379(dusp16.L) 108705035 108707492 108707826(dusp27.L) 108708221 108708849 108708878 108709322(mtmr4.S) 108709537 108709564 108710247 108710616 108710688(ptpro.L) 108711100 108711200(ptpn12.L) 108711310 108711853 108712239(dusp4.L) 108712367(ptprr.S) 108712382 108712565(dusp16.S) 108712781(dusp11.S) 108713150 108713433 108713595(ptprg.L) 108713695 108713793(ptpmt1.L) 108713914 108714090 108714619(dusp7.L) 108714727(cdc14b.L) ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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MIDDLETON - Chelsea Marie Merrill, 18, of Middleton, died from Lafora disease Monday, Aug. 18, 2014, at Frisbie Memorial Hospital, with her family and friends beside her.
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Expression of DUSP13 (BEDP, DUSP13A, DUSP13B, FLJ32450, TMDP) in small intestine tissue. Antibody staining with in immunohistochemistry.
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1EBB: Structure and Mechanism of Action of a Cofactor-Dependent Phosphoglycerate Mutase Homolog from Bacillus Stearothermophilus with Broad Specificity Phosphatase Activity.
DUSP23 Human Recombinant produced in E.coli is a single, non-glycosylated polypeptide chain containing 170 amino acids (1-150 a.a) and having a molecular mass of 18.8kDa.
Thats the thing about stab-happy goblins: you can never be sure quite when theyll pop up. Styx was meant to continue his merry little adventures in Styx:
Styx & Don Felder: Renegades in the Fast Lane is a stage production with an exclusive set list. Styx with Tommy Shaw, James JY Young, Lawrence Gowan, Todd Sucherman and Ricky Phillips, plus an occasional surprise appearance by original bassist Chuck Panozzo, is joined by Don Felder-formerly of the Eagles. The show pays tribute to their 45 plus years of rock bands and most illustrious guitar legends.
The Styx series born from Of Orcs and Men is looking to be a much better success than its predecessor. Here is our Styx Shards of Darkness review.
Supporters and owners of dogs affected by Lafora have been busy raising funds and have raised over £800 which will be split equally between research into the condition by the Canadian team and the Dachshund Breed Councils Health Fund. Contributions have come both from cash donations sent as a thank you for information and support,…
Mouse polyclonal antibody raised against a full-length human DUSP22 protein. DUSP22 (NP_064570.1, 1 a.a. ~ 184 a.a) full-length human protein. (H00056940-B01) - Products - Abnova
This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kise (DYRK) family. This member contains a nuclear targeting…
A brain injury involves medical and/or traumatic damage to the brain. An acquired brain injury results in loss of some previously learned skills or knowledge, and creates difficulties with new learning. There can be physical, sensory, cognitive, language, behavioral and/or emotional changes as a result of the injury. Car accidents, falls, strokes, brain tumors, concussions or lack of oxygen are some of the many situations that can injure the brain.. ...
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Fast delivery of DUSP9 knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
HIF-1 target DUSP2 is required for lapatinib resistance(A) Indicated cells were exposed to hypoxia for 6 hrs and cell lysates were collected for immunoblot anal
DUSP7 Polyclonal Antibody from Invitrogen for Western Blot and Immunohistochemistry applications. This antibody reacts with Human samples. Supplied as 400 µL purified antibody (Lot-specific) in PBS with 0.09% sodium azide.
Perform reliable qPCR with Bio-Rads pre-validated DUSP14 primer pair, for the Rabbit genome. Designed for SYBR Green-based detection.
This TSA-friendly travel kit includes six mini essentials all formulated with natural botanicals and nourishing vitamins. Find (MALIN+GOETZ) at Birchbox.
Purpose of log: Track progress on my journey from 173 lbs to 180 lbs. Round 1! Current stats: * Weight: 173 lbs * BF%: 14.8% * Cycle start date:
hi, i really want to lose weight before my birthday...ideally i would like to lose 35-40 lbs...by the end of july. but 25 lbs would be good enough...
This is a guide to EPM in horses. You can read of its prevention, whether it is contagious, which is the prognosis, if its curable and much more.
Hi all, just weighed myself after doing t/s for 2 weeks just 3 shakes a day and about 4ltrs of water daily and ive only lost 5lbs in the whole of 2...
Die LBS Westdeutsche Landesbausparkasse bedient mit ihren Finanzprodukten das Bundesland Nordrhein-Westfalen und ist die größte Landesbausparkasse Deutschlands.
MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression post-transcriptionally through complementary base pairing with thousands of messenger RNAs. Although the target genes and precise biological functions of individual miRNAs remain largely unknown, miRNAs are speculated to play important roles in diverse biological processes in both normal and pathological states. The liver is a vital organ that plays major roles in a number of physiological functions. Recent advances in the study of liver miRNAs using gene-modified mice or in vivo nucleic acid delivery to overexpress specific miRNAs or inhibit miRNA functions have revealed the crucial biological roles of individual miRNAs in physiologically essential liver functions in vivo. Because miRNA-based strategies are being applied to clinical therapeutics, the importance of precise knowledge of miRNA functions cannot be underestimated, not only from a scientific point of view, but also from a clinical perspective to make ...
Cellular microRNAs play an integral part in the post-transcriptional regulation of almost every cellular gene regulatory pathway and it therefore is not amazing that viruses have found ways to subvert this process. right now known that microRNAs (miRNAs) play key functions in the rules of almost every important cellular process in all multicellular eukaryotes3. Human being E-7010 cells encode over 1000 miRNA varieties, and these have been implicated in cellular differentiation, innate immunity, apoptosis and oncogenic transformation, as well as many other cell fate decisions3. Almost all cellular miRNAs are 1st transcribed as capped, polyadenylated main miRNA (pri-miRNA) transcripts that can encompass one or a cluster of ~22-nt miRNAs4. These miRNAs occupy the upper portion of an ~33-bp imperfect stem that is crowned by a large (10 nt) unstructured loop and flanked by solitary stranded RNA. This ~80-nt RNA structure is definitely identified by Rabbit polyclonal to nephrin. the nuclear ...
MicroRNAs are small noncoding RNAs that function by regulating target gene expression posttranscriptionally. They play a critical role in developmental and physiologic processes and are implicated in the pathogenesis of several human diseases including cancer. We examined the expression profiles of 241 human microRNAs in normal tissues and the NCI-60 panel of human tumor-derived cell lines. To quantify microRNA expression, we employed a highly sensitive technique that uses stem-loop primers for reverse transcription followed by real-time PCR. Most microRNAs were expressed at lower levels in tumor-derived cell lines compared with the corresponding normal tissue. Agglomerative hierarchical clustering analysis of microRNA expression revealed four groups among the NCI-60 cell lines consisting of hematologic, colon, central nervous system, and melanoma tumor-derived cell lines clustered in a manner that reflected their tissue of origin. We identified specific subsets of microRNAs that provide ...
Background: Dilated cardiomyopathy (DCM) is the most common heart disease in Doberman Pinschers. MicroRNAs (miRNAs) are short non-coding RNAs playing important roles in gene regulation. Different miRNA expression patterns have been described for DCM in humans and might represent potential diagnostic markers. There are no studies investigating miRNA expression profiles in canine DCM. The aims of this study were to screen the miRNA expression profile of canine serum using miRNA microarray and to compare expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Results: Eight Doberman Pinschers were examined by echocardiography and 24-hour-ECG and classified as healthy (n = 4) or suffering from DCM (n = 4). Total RNA was extracted from serum and hybridized on a custom-designed 8x60k miRNA microarray (Agilent) containing probes for 1368 individual miRNAs. Although total RNA concentrations were very low in serum samples, 404 different miRNAs were detectable with sufficient ...
Background: MicroRNAs are small non-coding RNAs that play crucial roles in the pathogenesis of different cancer types. The aim of this study was to identify miRNAs that are differentially expressed in endometrial adenocarcinoma compared to healthy endometrium. These miRNAs can potentially be used to develop a panel for classification and prognosis in order to better predict the progression of the disease and facilitate the choice of treatment strategy.. Methods Formalin fixed paraffin embedded endometrial tissue samples were collected from the Örebro university hospital. QPCR was used to quantify the expression levels of 742 miRNAs in 30 malignant and 20 normal endometrium samples. After normalization of the qPCR data, miRNAs differing significantly in expression between normal and cancer samples were identified, and hierarchical clustering analysis was used to identify groups of miRNAs with coordinated expression profiles.. Results: In comparisons between endometrial adenocarcinoma and normal ...
microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. Prior studies have shown that they regulate numerous physiological processes critical for normal development, cellular growth control, and organismal behavior. Here, we systematically surveyed 134 different miRNAs for roles in olfactory learning and memory formation using sponge technology to titrate their activity broadly in the Drosophila melanogaster central nervous system. We identified at least five different miRNAs involved in memory formation or retention from this large screen, including miR-9c, miR-31a, miR-305, miR-974, and miR-980. Surprisingly, the titration of some miRNAs increased memory, while the titration of others decreased memory. We performed more detailed experiments on two miRNAs, miR-974 and miR-31a, by mapping their roles to subpopulations of brain neurons and testing the functional involvement in memory of potential mRNA targets through bioinformatics and a RNA interference
article{90157528-095c-47de-87a4-ca0e72eaa265, abstract = {,p,MicroRNAs are small non-coding RNAs, which negatively regulate the expression of target genes. They have emerged as important modulators in beta cell compensation upon increased metabolic demand, failure of which leads to reduced insulin secretion and type 2 diabetes. To elucidate the function of miRNAs in beta cells, insulin-secreting cell lines, such as the rat insulinoma INS-1 832/13 and the human EndoC-βH1, are widely used. Previous studies in the cancer field have suggested that miRNA expression is influenced by confluency of adherent cells. We therefore aimed to investigate whether one of the most enriched miRNAs in the pancreatic endocrine cells, miR-375, and two of its validated targets in mouse, Cav1 and Aifm1, were differentially-expressed in cell cultures with different confluences. Additionally, we measured the expression of other miRNAs, such as miR-152, miR-130a, miR-132, miR-212 and miR-200a, with known roles in beta ...
The role of obesity in regulation of microRNA (miRNA) expression in distal and proximal colon was assessed: 1) isolation and quantification methods for miRNAs were established in rat liver tissue; 2) miRNA expression patterns were compared using miRNA PCR arrays in lean proximal and distal colonic tissue; and 3) the influence of obesity on miRNA expression in these colonic regions was investigated by screening cancer miRNA coding genes in colonic mucosal samples from Zucker obese and lean rats. Up-regulation of 20 miRNAs was observed in obese liver tissue. Colonic mucosal miRNA expression patterns and abundance differed for distal and proximal colonic regions in both lean and obese tissue. Obesity exerted a profound region-specific effect on miRNA expression patterns and levels indicating biologically distinct tissue in distal and proximal colon. Obesity markedly affects miRNA gene regulation, and miRNA is a key molecular player in the genesis of colon cancer.
MicroRNAs (miRNAs) are endogenously expressed single-stranded ∼21-23 nucleotide RNAs that inhibit gene expression post-transcriptionally by binding imperfectly to elements usually within the 3′untranslated region (3′UTR) of mRNAs. Small interfering RNAs (siRNAs) mediate site-specific cleavage by binding with perfect complementarity to RNA. Here, a cell-based miRNA reporter system was developed to screen for compounds from marine and plant extracts that inhibit miRNA or siRNA activity. The daphnane diterpenoid genkwanine M (GENK) isolated from the plant Wikstroemia polyantha induces an early inflammatory response and can moderately inhibit miR-122 activity in the liver Huh-7 cell line. GENK does not alter miR-122 levels nor does it directly inhibit siRNA activity in an in vitro cleavage assay. Finally, we demonstrate that GENK can inhibit HCV infection in Huh-7 cells. In summary, the development of the cell-based miRNA sensor system should prove useful in identifying compounds that affect miRNA
Hantaviruses cause serious human diseases, Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS), depending on the virus type. Currently no vaccine exists and the existing drug therapy for hantavirus infections is mainly supportive. MicroRNAs are short non-coding RNAs that regulate gene expression. They play important roles in many biological processes, including cell differentiation, development and diseases like cancer. miRNAs have also been found to be involved in viral infections. The aim of this project was to investigate the miRNA expression during Hantavirus infection, and analyze the difference in miRNA expression between pathogenic hantaviruses (Hantaan virus), non-pathogenic (Prospect Hill virus), and mock-infected cells. Aberrantly expressed miRNAs could have potential as therapeutic targets.Focus assay was used to quantify the virus, and a stay in Berlin was organized to get instructions from Dr. Rang. However, the optimization of the assay was not ...
Although microRNAs (miRNAs) play an important role in liver homeostasis, the extent to which they can be altered by Toxoplasma gondii infection is unknown. Here, we utilized small RNA sequencing and bioinformatic analyses to characterize miRNA expression profiles in the liver of domestic cats at 7 days after oral infection with T. gondii (Type II) strain. A total of 384 miRNAs were identified and 82 were differentially expressed, of which 33 were up-regulated and 49 down-regulated. Also, 5690 predicted host gene targets for the differentially expressed miRNAs were identified using the bioinformatic algorithm miRanda. Gene ontology analysis revealed that the predicted gene targets of the dysregulated miRNAs were significantly enriched in apoptosis. Kyoto Encyclopedia of Genes and Genomes analysis showed that the predicted gene targets were involved in several pathways, including acute myeloid leukemia, central carbon metabolism in cancer, choline metabolism in cancer, estrogen signaling pathway, ...
Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. ...
Background MicroRNAs (miRNAs) are small non-coding RNAs (18-24 nucleotides) that have recently been shown to regulate gene expression during cancer progression. Dicer, a central enzyme in the multi-component miRNA biogenesis pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence shows that Dicer expression is deregulated in some human malignancies and it correlates with tumor progression, yet this role has not yet been investigated in skin cancers. Methods and Findings Using an anti-human monoclonal antibody against Dicer and immunohistochemistry, we compared the expression of Dicer protein among 404 clinically annotated controls and skin tumors consisting of melanocytic nevi (n = 71), a variety of melanomas (n = 223), carcinomas (n = 73) and sarcomas (n = 12). Results showed a cell-specific up-regulated Dicer in 81% of cutaneous, 80% of acrolentiginous and 96% of metastatic melanoma specimens compared to carcinoma or sarcoma specimens (P|0.0001
In this study, we demonstrated that serum levels of the microRNAs, miR-192, miR-194, and miR-34a, are upregulated as early as a median of 18 days after AMI onset in patients who survived AMI but experienced development of HF within 1 year. Furthermore, circulating miR-194 and miR-34a levels in the convalescent stage of AMI were associated with left ventricular diastolic dimension. Thus, these p53-responsive microRNAs may be useful for stratifying the risk of future ischemic HF events and cardiac remodeling in post-AMI patients.. Because the expression levels of the 3 identified microRNAs were well-correlated with each other, it is conceivable that their expression was coordinately upregulated in a single cascade. One of the most likely candidates for an inducer of this coordinated expression is the tumor suppressor p53, because all 3 microRNAs are reported to be induced by the direct binding of p53 to the promoter regions of the corresponding genes.8,9 In particular, it was recently demonstrated ...
MicroRNAs (miRNAs) play essential roles in muscle cell proliferation and differentiation. The muscle-specific miRNAs miR-1 and miR-206 have been shown to regulate muscle development and promote myogenic differentiation; however, it is likely that a number of other miRNAs play important roles in regulating myogenesis as well. microRNA-128 (miR-128) has been reported to be highly expressed in brain and skeletal muscle, and we found that miR-128 is also up-regulated during bovine skeletal muscle satellite cell differentiation using microarray analysis and qRT-PCR. However, little is known about the functions of miR-128 in bovine skeletal muscle satellite cell development. In this study, we investigated the biological functions of miR-128 in bovine skeletal muscle cell development. Using a dual-luciferase reporter assay, we confirmed that miR-128 regulates the Sp1 gene. Over-expression of miR-128 reduced Sp1 protein levels and inhibited muscle satellite cell proliferation and differentiation. ...
MicroRNAs (miRNAs) represent a group of small, non-coding RNA molecules that have been shown to regulate gene expression at the translational level by interfering with the 3 untranslated region of messenger RNAs. Gene silencing through miRNA interference is one epigenetic mechanism impacting the development and homeostasis of the organism. MiRNAs are critical for regulation of several biological processes, cellular function, the cell cycle, differentiation and apoptosis. Deregulation of miRNAs was confirmed in several pathologies including cancer (in lung cancer among others), asthma, COPD, diabetes and cardiovascular diseases. In mice models of asthma it has been found that increased levels of miR-21 and miR-126, and decreased levels of miR-672 and miR-143 are associated with regulation of cytokines involved in inflammation and remodeling, namely Il-13, Il-12, Il-10 and matrix metalloproteinase-12 (MMP-12). In lung cancer, overexpression of several miRNAs (miR-155, miR21, miR-17-92, ...
Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is a major public health problem in poor and developing countries of the Americas, Africa, and Asia. MicroRNAs (miRNAs), which are small non-coding RNAs (18-24 nucleotides), play an important role in regulating cell and tissue homeostasis through translational downregulation of messenger RNAs. Deregulation of miRNA expression is important for the pathogenesis of a wide variety of neoplastic and non-neoplastic diseases, and has been the focus of many publications; however, studies on the expression of miRNAs in leprosy are rare. Herein, an extensive evaluation of differentially expressed miRNAs was performed on leprosy skin lesions using microarrays. Leprosy patients, classified according to Ridley & Joplings classification or reactional states (R1 and R2), and healthy controls (HC) were included. Punch biopsies were collected from the borders of leprosy lesions (10 tuberculoid, 10 borderline tuberculoid, 10 borderline borderline, 10
To gain a comprehensive understanding of tumorigenesis, it is critical to integrate findings on factors that regulate the transcriptome, such as microRNAs, with genomic analysis. This is especially pertinent in the case of pediatric CNS tumors, which have fewer mutational events than their adult counterparts [48, 54]. MicroRNAs are highly regulated and have essential functions in brain development [23, 30], and certain microRNAs are enriched or specifically expressed in the adult brain [49]. Here, we profiled microRNA and gene expression in a cohort of pediatric brain tumors, and then focused on the potential role of microRNAs in pilocytic astrocytomas.. The mitogen-activated protein kinase (MAPK) signaling cascade is the main molecular pathway that is deregulated in pilocytic astrocytomas [56]. BRAF-gene fusions and, in rare cases, BRAF V600E mutations give rise to constitutively active BRAF, which in turn activates the MAPK pathway. Furthermore, BRAF activation has been shown to cause ...
Scientists from the Department of Neuroscience, Area Drug and Child Health (NEUROFARBA) at the University of Florence and Chiesi Pharmaceuticals report that extra virgin olive oil rich in polyphenols was associated with "strong" improvements in coordination, memory, and anxiety-related behavior in older lab mice.. The polyphenol-rich olive oil was found to change the expression of micro RNA (miRNA) - a small non-coding RNA molecule that plays a role in gene expression - and produce profiles similar to those observed in young mice, according to data published in the European Journal of Nutrition​​.. "In a nutraceutical perspective, the long-term treatment with olive oil phenols could become part of a neuroprotective strategy for the prevention of brain aging, mediated by the induction of health-promoting genes and the coordinated modulation of miRNA profiles,"​ wrote the authors, led by Dr Cristina Luceri.. Study details​. Dr Luceri and her co-workers used 10 month old (middle-aged) lab ...
Researchers recently studied a highly sophisticated cellular machine that acts as a guard for the genome against harmful mutations and that evolution cannot explain.1. Humans have two sets of 23 chromosomes, and a mutational deletion in chromosome 22 causes a disease called DiGeorge syndrome in which heart and immune system defects occur, in addition to learning difficulties, mental retardation, and psychiatric disorders. The deletion eliminates a protein and stops the formation of a key piece of cellular machinery called a microprocessor.. The microprocessor is actually a working complex of two important proteins called Drosha and DGCR8 (DiGeorge syndrome critical region 8). The mutation causing the microprocessor to be defective affects DGCR8.2 The microprocessor protein complex itself gets its name from the fact that it processes an important group of molecules called microRNAs. MicroRNAs are small molecules that help regulate gene expression.3. It turns out that the microprocessor does ...
Micro-RNAs (miRNAs) belong to a class of small non-coding messenger RNA species that have emerged as potent regulators of a variety of biological processes including oncogenesis. They serve as master regulators with a single miRNA capable of regulating as many as 100 different target genes. Thyroid carcinomas encompass a wide spectrum ranging from well-differentiated thyroid carcinomas to poorly differentiated and anaplastic carcinoma. Currently, a considerable degree of interobserver variability exists in the morphological diagnosis of certain types of thyroid carcinomas especially the follicular pattern neoplasm. The prediction of progression of these differentiated carcinoma to more aggressive forms like poorly differentiated and anaplastic types is of considerable interest to physicians and pathologists for determining prognosis and making therapeutic decisions. Several investigators have proposed a more cohesive approach to thyroid cancer diagnosis incorporating molecular and proteomics ...
MicroRNAs (miRNAs) play key roles in regulating zinc (Zn) toxicity tolerance in plants. Solanum nigrum is a typical Zn/Cd-accumulating plant that has a high Zn/Cd tolerance. Despite their importance, no miRNAs have been identified from S. nigrum thus far. In this study, small RNA sequencing was used to identify Zn-responsive miRNAs in S. nigrum roots. We identified 176 differentially expressed miRNAs in S. nigrum roots in response to Zn toxicity. We also found that all these differentially expressed Zn-miRNAs simultaneously respond to the exogenous NO donor sodium nitroprusside (SNP), indicating that NO is involved in Zn-mediated miRNA expression in S. nigrum. These differentially expressed miRNAs are involved in regulating the following processes in S. nigrum roots: phenylpropanoid catabolic and metabolic processes; lignin catabolic and metabolic processes; and programmed cell death in response to ROS. These results suggest that these miRNAs play key roles in the Zn toxicity tolerance of S. ...
by Chun Zhao, Jing Dong, Tao Jiang, Zhonghua Shi, Bin Yu, Yunlong Zhu, Daozhen Chen, Junrong Xu, Ran Huo, Juncheng Dai, Yankai Xia, Shiyang Pan, Zhibin Hu, Jiahao Sha. Background Gestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM.. Methodology/Principal Findings We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our ...
Wnt signaling through β-catenin and the lymphoid-enhancing factor 1/T-cell factor (LEF1/TCF) family of transcription factors maintains stem cell properties in both normal and malignant tissues; however, the underlying molecular pathway involved in this process has not been completely defined. Using a microRNA microarray screening assay, we identified the let-7 miRNAs as downstream targets of Wnt/β-catenin pathway. Expression studies indicated that Wnt/β-catenin pathway suppresses mature let-7 miRNAs but not the primary transcripts, which suggests a posttranscriptional regulation of repression. Furthermore, we identified Lin28, a negative let-7 biogenesis regulator, as a novel direct downstream target of Wnt/β-catenin pathway. Loss of function of Lin28 impairs the Wnt/β-catenin pathway-mediated let-7 inhibition and breast cancer stem cell expansion; enforced expression of let-7 blocks the Wnt/β-catenin pathway-stimulated breast cancer stem cell phenotype. Finally, we demonstrated that ...
Ionizing radiation (IR) is widely used in cancer treatment and in biological studies. It disrupts cellular homeostasis through multiple mechanisms including changes of the expression profile of genes. Although microRNAs (miRNAs) have recently been recognized as important post-transcriptional regulators and are involved in various biological processes, whether miRNAs play any roles in the cellular response to IR, is not well examined. We investigated the profile of miRNA expression following IR in the human lung carcinoma cell line A549, and the expression profiles of IR-responsive miRNAs were confirmed by qRT-PCR. The target mRNAs of IR-responsive miRNAs were predicted with a target prediction tool. Microarray analysis identified 12 and 18 miRNAs in 20- and 40 Gy-exposed A549 cells, respectively, that exhibited more than 2-fold changes in their expression levels. Of these, four were changed in only 20-Gy-treated cells, ten only in 40-Gy-treated cells, and eight miRNAs were found to change after ...
Extracellular microRNAs (miRNAs) are promising biomarkers of the inherited muscle wasting condition Duchenne muscular dystrophy, as they allow non-invasive monitoring of either disease progression or response to therapy. In this study, serum miRNA profiling reveals a distinct extracellular miRNA signature in dystrophin-deficient mdx mice, which shows profound dose-responsive restoration following dystrophin rescue. Extracellular dystrophy-associated miRNAs (dystromiRs) show dynamic patterns of expression that mirror the progression of muscle pathology in mdx mice. Expression of the myogenic miRNA, miR-206 and the myogenic transcription factor myogenin in the tibialis anterior muscle were found to positively correlate with serum dystromiR levels, suggesting that extracellular miRNAs are indicators of the regenerative status of the musculature. Similarly, extracellular dystromiRs were elevated following experimentally-induced skeletal muscle injury and regeneration in non-dystrophic mice. Only a minority
MicroRNAs (miRNAs) are a class of small non-coding RNAs that, in general, negatively regulate gene expression. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. Some miRNA genes harboring CpG islands undergo methylation-mediated silencing, a characteristic of many tumor suppressor genes. To identify such miRNAs in hepatocellular carcinoma (HCC), we first examined the methylation status of 43 loci containing CpG islands around 39 mature miRNA genes in a panel of HCC cell lines and non-cancerous liver tissues as controls. Among 11 miRNA genes frequently methylated in HCC cell lines but not in non-cancerous liver tissues, three miRNA genes, i.e. miR-124, miR-203 and miR-375, were selected as silenced miRNAs through CpG-island methylation by comparing methylation and expression status and evaluating restored expression after treatment with 5-aza-2′-deoxycytidine. In primary tumors of HCC with paired non-tumorous ...
Using gene expression analyses, overexpression of the cyclin D genes seems to be one possible unifying event that is seen in almost all multiple myeloma cases with or without an immunoglobulin translocation as compared with normal plasma cells (30). IgH translocations directly dysregulate cyclin D1 or D3 [t(11;14) and t(6;14), respectively] and the C-MAF or MAFB transcription factors dysregulate cyclin D2 [t(14;16) and t(14;20); ref. 31]. In this study, 12 MGUS samples had a similar pattern of cyclin D dysregulation despite a lower proliferative index, suggesting that cyclin D perturbation may indeed be an early and unifying event in plasma cell dyscrasias.. MicroRNAs (miRNA) are single-stranded RNA molecules that regulate gene expression posttranscriptionally and are being implicated in a large number of cancers (32). A study comparing miRNA profiles of normal plasma cells (PC), MGUS, SMM, and multiple myeloma found overexpression of mir-21, mir-106∼25, and mir181a, and mir-181b in MGUS and ...
Purpose: : FGF signaling controls numerous processes during cell lineage specification, organogenesis and terminal differentiation. In lens, FGF signaling was implicated as the key pathway that controls lens fiber cell differentiation, but little is known about its nuclear components such as DNA-binding transcription factors and its cross-talk with other signaling pathways that function downstream and/or in parallel with FGF signaling. Methods: : We employed a rat lens epithelial explant system and performed integrated RNA and microRNA expression profiling in cells induced to differentiate by FGF2 (100 ng/ml). The RNAs were isolated at 2, 4, 12 and 24 hours following the treatment. RNA expression profiling was conducted using rat Affymetrix 230 2.0 arrays. MicroRNA profiling was conducted using the rodent TaqMan Low Density Array v2 ABI system. Candidate microRNA targets were identified through a combination of TargetScan 5.0 and integrated prediction databases in miRWalk and by inverse ...
Volatile organic compounds (VOCs) are one of main pollutants indoors. Exposure to VOCs is associated with cancer, asthma disease, and multiple chemical allergies. Despite the adverse health effects of VOCs, the molecular mechanisms underlying VOCs-induced disease remain largely unknown. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, may influence cellular disease state. To investigate whether lung miRNA expression profiles in mice are modified by VOCs mixture exposure, 44 male Kunming mice were exposed in 4 similar static chambers, 0 (control) and 3 different doses of VOCs mixture (groups 1¡V3). The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 3.0 + 3.3 + 6.0 + 6.0 mg/m3, 5.0 + 5.5 + 10.0 + 10.0 mg/m3, 10.0 + 11.0 + 20.0 + 20.0 mg/m3, respectively, which corresponded to 30, 50, and 100 times of indoor air quality standard in China, after exposure to 2 weeks (2 h/day, 5 days/week). Small RNAs in lung and protein ...
In this study we characterized miRNA expression profiles in equine epiphyseal cartilage and subchondral bone using NGS analysis. We identified 609 and 622 miRNAs expressed in cartilage and bone, respectively, including about 300 novel miRNAs. Recently, Sun et al., described the use of a Solexa-based deep sequencing approach to identify miRNAs profiles of articular cartilage from rat femoral head cartilage. This study made it possible to highlight 310 known miRNAs as well as 86 novel miRNAs candidates [32]. Since 215 miRNA are found in common with the present study, our results extend the repertoire of miRNA expressed in cartilage by adding 111 additional miRNAs. We provide a comprehensive repertoire of miRNAs expressed in both cartilage and bone samples collected in vivo. In particular, our results highlighted numerous new putative highly expressed miRNAs based on a high confidence RNA-fold score. Most of these also display orthologous precursor sequences in at least one other mammalian genome. ...
Development of resistance to androgen deprivation therapy (ADT) is a major obstacle for the management of advanced prostate cancer. Therapies with androgen receptor (AR) antagonists and androgen withdrawal initially result in tumor regression but development of compensatory mechanisms including AR bypass signaling leads to tumor re-growth, independent of circulating androgens. The result is the emergence of castration resistant prostate cancer (CRPC), a highly morbid disease exhibiting aberrant expression of many protein-coding and non-coding genes. Under the umbrella of non-coding RNAs is a class of small regulatory RNAs referred to as microRNAs (miRNAs). MicroRNAs are believed to function in the maintenance of cell homeostasis but are often differentially expressed in many different types of cancer including CRPC. In this study, the association of genome wide miRNA expression (1113 unique miRNAs) with development of resistance to ADT was determined. Androgen sensitive prostate cancer cells that
The microRNA (miRNA) pathway is well established to be involved in host-pathogen interactions. As key insect pollinators, bees are suffering from widely spreading viruses, especially honeybees and bumblebees. In order to better understand bee-virus interaction, we comparatively analyzed the involvement of the bumblebee miRNA pathway upon infection by two different viruses. In our setup, an avirulent infection is induced by slow bee paralysis virus (SBPV) and a virulent infection is induced by Israeli acute paralysis virus (IAPV). Our results showed the increased expressions of dicer-1 and ago-1 upon SBPV infection. There were 17 and 12 bumblebee miRNAs differentially expressed upon SBPV and IAPV infections, respectively. These results may indicate the involvement of the host miRNA pathway in bumblebee-virus interaction. However, silencing of dicer-1 did not influence the genome copy number of SBPV. Target prediction for these differentially expressed miRNAs showed their possible involvement in ...
Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling. Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both. miR-17-3p ... read more promoted cardiomyocyte hypertrophy, proliferation, and survival. TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p. Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation. Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury. Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling. miR-17-3p may ...
Autologous hematopoietic stem cell transplantation (aHSCT) has been used as a therapeutic approach in multiple sclerosis (MS). However, it is still unclear if the immune system that emerges from autologous CD34+ hematopoietic progenitor cells (HPC) of MS patients is pre-conditioned to re-develop the proinflammatory phenotype. The objective of this article is to compare the whole genome gene and microRNA expression signature in CD34+ HPC of MS patients and healthy donors (HD). CD34+ HPC were isolated from peripheral blood of eight MS patients and five HD and analyzed by whole genome gene expression and microRNA expression microarray. Among the differentially expressed genes (DEGs) only TNNT1 reached statistical significance (logFC=3.1, p,0.01). The microRNA expression was not significantly different between MS patients and HD. We did not find significant alterations of gene expression or microRNA profiles in CD34+ HPCs of MS patients. Our results support the use of aHSCT for treatment of MS. ...
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Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease which is associated with pulmonary arterial endothelial cells (PAEC) dysfunction and pulmonary arterial smooth muscle cells proliferation. Moreover, inflammation is contributing a critical role in EC dysfunction and remains elusive. Nuclear factor-kappa B (NF-κB) is a master transcriptional regulator in various cardiovascular pathologies; but, NF-κBs role in EC dysfunction in unknown. Our previous study using cardiac and lung specific IκBα mutant mice (3M and IKBM) showed that PAH induced right ventricular hypertrophy (RVH) was prevented in monocrotaline (MCT) treated 3M and IKBM mice, compared to the wild-type mice. Recently, microRNAs (miRNAs) have emerged as a new class of post-transcriptional regulators in vascular remodeling; but, NF-κB regulated miRNA modulation in EC dysfunction is unknown. Using miRNA array analysis, we identified miR-130a which is upregulated in MCT-induced PAH mouse model, as a ...
Small interfering RNAs (siRNAs), microRNAs (miRNAs), and piRNAs (piRNA) are conserved classes of small single-stranded ~21-30 nucleotide (nt) RNA guides that repress eukaryotic gene expression using distinct RNA Induced Silencing Complexes (RISCs). At its core, RISC is composed of a single-stranded small RNA guide bound to a member of the Argonaute protein family, which together bind and repress complementary target RNA. miRNAs target protein coding mRNAs-a function essential for normal development and broadly involved in pathways of human disease; small interfering RNAs (siRNA) defend against viruses, but can also be engineered to direct experimental or therapeutic gene silencing; piwi associated RNAs (piRNAs) protect germline genomes from expansion of parasitic nucleic acids such as transposons. Using the fruit fly, Drosophila melanogaster, as a model organism we seek to understand how small silencing RNAs are made and how they function. In Drosophila, miRNAs and siRNAs are proposed to have parallel,
Researchers at Duke University Medical Center may finally have discovered why people with sickle cell disease get milder cases of malaria than individuals who have normal red blood cells.. The paper shows that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. ". "One of the most interesting findings in our study is that the human microRNA found in sickle red cells directly participate in the gene regulation of malaria parasites," said Dr. Jen-Tsan Chi, M.D., Ph.D., senior author and associate professor in the Duke Institute for Genome Sciences and Policy and Department of Molecular Genetics and Microbiology. "These microRNAs enriched in the sickle red cells reduce the parasites ability to propagate, so that certain people stay more protected.". During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and ...
Bone marrow-derived endothelial progenitor cells (EPC) contribute to the angiogenesis-dependent growth of tumors in mice and humans. EPCs regulate the angiogenic switch via paracrine secretion of proangiogenic growth factors and by direct luminal incorporation into sprouting nascent vessels. miRNAs have emerged as key regulators of several cellular processes including angiogenesis; however, whether miRNAs contribute to bone marrow-mediated angiogenesis has remained unknown. Here, we show that genetic ablation of miRNA-processing enzyme Dicer, specifically in the bone marrow, decreased the number of circulating EPCs, resulting in angiogenesis suppression and impaired tumor growth. Furthermore, genome-wide deep sequencing of small RNAs revealed tumor EPC-intrinsic miRNAs including miR-10b and miR-196b, which have been previously identified as key regulators of HOX signaling and adult stem cell differentiation. Notably, we found that both miR-10b and miR-196b are responsive to vascular endothelial growth
Introduction: Recent studies suggest an association between changes in platelet-specific microRNAs (miRs) and changes in platelet reactivity. However, molecular pathways that govern platelet reactivity are incompletely characterized. We hypothesize that miRs expressed in plasma are associated with measured platelet reactivity in the TRILOGY-ACS cohort and highlight the genomic regulatory architecture of platelet reactivity.. Methods: The study included 712 patients with non-ST elevation acute coronary syndrome (NSTEACS) enrolled in the TRILOGY-ACS trial. Plasma samples collected prior to anti-platelet therapy randomization were used to determine P2Y12 Reaction Units (PRU) measured on the VerifyNow system as well as the concentration of 35 miR species known to be involved in cardiovascular development and disease. We tested for association between PRU and miR expression using multivariable linear regression, adjusting for age, sex, race, prior clopidogrel and aspirin status, diabetes and ...
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Argonaute 1 (Ago1) is a member of the Argonaute/PIWI protein family involved in small RNA-mediated gene regulation. In . Drosophila, Ago1 plays a specific role in microRNA (miRNA) biogenesis and function. Previous studies have demonstrated that Ago1 regulates the fate of germline stem cells. However, the function of Ago1 in other aspects of oogenesis is still elusive. Here we report the function of Ago1 in developing egg chambers. We find that Ago1 protein is enriched in the oocytes and is also highly expressed in the cytoplasm of follicle cells. Clonal analysis of multiple . ago1 mutant alleles shows that many mutant egg chambers contain only 8 nurse cells without an oocyte which is phenocopied in . dicer-1, . pasha and . drosha mutants. Our results suggest that Ago1 and its miRNA biogenesis partners play a role in oocyte determination and germline cell division in . Drosophila. © 2012.
NanoStringNorm: an extensible R package for the pre-processing of NanoString mRNA and miRNA data: Motivation: The NanoString nCounter Platform is a new and promising technology for measuring nucleic acid abundances. It has several advantages over PCR-based techniques, including avoidance of amplification, direct sequence interrogation and digital detection for absolute quantification. These features minimize aspects of experimental error and hold promise for dealing with challenging experimental conditions such as archival formalin-fixed paraffin-embedded samples. However, systematic inter-sample technical artifacts caused by variability in sample preservation, bio-molecular extraction and platform fluctuations must be removed to ensure robust data.. Results: To facilitate this process and to address these issues for NanoString datasets, we have written a pre-processing package called NanoStringNorm in the R statistical language. Key features include an extensible environment for method ...
PHILADELPHIA and REHOVOT, Israel, Feb. 7, 2013 /PRNewswire/ -- Rosetta Genomics Ltd. , a leading developer and provider of microRNA-based molecular diagnostics, today announced that data from a study demonstrating the ability of microRNA expression to serve as a biomarker to predict the progression of bladder urothelial carcinoma were published online in the British Journal of Urology International, in an article entitled, Predicting progression of bladder urothelial carcinoma using microRNA
Breast cancer is one of the most common solid tumors in women involving multiple subtypes. However, the mechanism for subtypes of breast cancer is still complicated and unclear. Recently, several studies indicated that long non-coding RNAs (lncRNAs) could act as sponges to compete miRNAs with mRNAs, participating in various biological processes.. Researchers at the Nanjing University of Aeronautics and Astronautics concentrated on the competing interactions between lncRNAs and mRNAs in four subtypes of breast cancer (basal-like, HER2+, luminal A and luminal B), and analyzed the impacts of competing endogenous RNAs (ceRNAs) on each subtype systematically. They constructed four breast cancer subtype-related lncRNA-mRNA ceRNA networks by integrating the miRNA target information and the expression data of lncRNAs, miRNAs and mRNAs.. The research team constructed the ceRNA network for each breast cancer subtype. Functional analysis revealed that the subtype-related ceRNA networks were enriched in ...
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: A Cancer Journal for Clinicians. 2016;66:7-30 2. Eddy SR. Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2001;2:919-29 3. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843-54 4. Sai Lakshmi S, Agrawal S. piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Research. 2008;36:D173-D7 5. Scott MS, Ono M, Yamada K, Endo A, Barton GJ, Lamond AI. Human box C/D snoRNA processing conservation across multiple cell types. Nucleic Acids Research. 2011;40:3676-88 6. Cao J. The functional role of long non-coding RNAs and epigenetics. Biological Procedures Online. 2014;16:11 7. Moyano M, Stefani G. piRNA involvement in genome stability and human cancer. Journal of Hematology & Oncology. 2015:8 8. Thomson T, Lin H. The Biogenesis and Function PIWI Proteins and piRNAs: Progress and Prospect. Annual ...
Certain microRNAs (miRs) have important roles in the maintenance of bone development and metabolism, and a variety of miRs are known to be deregulated in diabetes. The present study investigated the role of miR‑203‑3p in the regulation of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The results indicated that miR‑203‑3p inhibited osteogenesis in the jaws of diabetic rats and in rat bone marrow mesenchymal stem cells cultured in high‑glucose medium. A luciferase re-porter assay was used to verify the bioinformatics prediction that miR‑203‑3p targets the 3‑untranslated region of Smad1, which is an important mediator of the bone morphogenetic protein (BMP)/Smad pathway ...
MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family was also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b, and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB, and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3,
Prostate removal is widely utilized to treat men with early-stage disease. However, up to 30-40% of patients experience rising PSA levels, which are currently used as indicators of tumor recurrence, following surgery. These patients are commonly treated with radiation therapy.. The researchers analyzed tumor samples taken from 43 prostate cancer patients who all later received radiation therapy after rising PSA levels were detected following prostatectomy.. The study indicated that a pattern of miRNAs in tumor cells might allow successful prediction of patients responses to radiation therapy. Two miRNAs in particular, termed miR-4516 and miR-601, were highlighted as potentially useful for identifying patients who might experience rising PSA following radiation therapy, along with Gleason score and lymph node status.. "This study is the first to demonstrate that miRNA expression in tumor cells correlates with outcome after salvage radiation therapy, paving the way for the potential use of miRNA ...
Investigation of the molecular signatures of primary human breast cancers has identified distinct subtypes that include the basal-like subtype, which is aggressive, poorly differentiated, associated with poor clinical outcomes, and contribute disproportionately to breast cancer mortality. These cancers are associated with a high likelihood of relapse, and lack targeted therapeutic approaches. Recent studies from our laboratory found that most basal-like breast cancers express a hypermethylation defect that involves hyperactivity of the DNA methylation machinery and overexpression of DNA methyltransferase 3b (DNMT3b). We hypothesize that the unique clinical features of basal-like breast cancers may be a direct consequence of aberrant gene expression patterns resulting from methylation-dependent gene silencing events. The mechanisms that govern dysregulation of DNMT3b in breast cancer are unknown. However, studies in other tumor systems suggest strongly that alterations in regulatory microRNAs can ...
A personal computers microprocessor is time-shared to provide the functions formerly provided by a microprocessor dedicated to a modem. This technique is transparent to software applications programs which interact with a modem. The personal computer utilizes an operating system, such as the Microsoft Windows operating system, in which a portion of the operating system, known as the communications driver, provides the interface between the operating system and the personal computers serial and parallel communication ports. All communications between the communications driver and the rest of the operating system are examined. Those communications destined for a particular port associated with a modem not having a dedicated microprocessor are redirected while other communications destined for other ports are passed to the Microsoft Windows communications driver. The redirected communications are coupled to a software application program which utilizes the PC microprocessor to carry out the functions
Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene (nuclear receptor subfamily 1, group H, member 3). miRNA has-miR-613 autoregulates the human LXRα gene by targeting the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3′-untranslated region. LXRα autoregulates its own suppression via induction of SREBP1c which upregulates miRNA has-miR-613. The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases. The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with ...
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At this time, the available peer-reviewed published literature addressing the clinical benefit of a microprocessor controlled lower limb prostheses is mostly limited to nonrandomized controlled clinical trials, and case series of limited size. Additionally, the majority of these studies have involved highly selected subjects who were otherwise in good health. Microprocessor Controlled Knee Prosthesis One publication by Hafner and others (2007) reports the findings of a small, nonrandomized, cross-over controlled design study in which each subject was exposed to two different prosthetic limb conditions (mechanical and microprocessor controlled C-Leg) twice during the trial. This study included 21 subjects, each of whom used both a standard mechanical knee and lower limb prosthesis and the C-Leg microprocessor controlled prosthesis. Subjects were recruited for participation from a local amputee population. Seventeen subjects completed the study. Subjects were told at the time of enrollment that ...
Parasitic infections remain one of the most pressing global health concerns of our day, affecting billions of people and producing unsustainable economic burdens. The rise of drug-resistant parasites has created an urgent need to study their biology in hopes of uncovering new potential drug targets. It has been established that disrupting gene expression by interfering with lysine acetylation is detrimental to survival of apicomplexan (Toxoplasma gondii and Plasmodium spp.) and kinetoplastid (Leishmania spp. and Trypanosoma spp.) parasites. As "readers" of lysine acetylation, bromodomain proteins have emerged as key gene expression regulators and a promising new class of drug target. Here we review recent studies that demonstrate the essential roles played by bromodomain-containing proteins in parasite viability, invasion, and stage switching and present work showing the efficacy of bromodomain inhibitors as novel antiparasitic agents. In addition, we performed a phylogenetic analysis of ...
Most prokaryotes and archaeans use the same RNA polymerase to transcribe mRNA and functional non-coding RNAs (e.g. ribosomal RNAs or transfer RNAs). Whereas eukaryotes (organisms in which the genetic material is contained within a nucleus) use specialized RNAPs, each responsible for transcribing different classes of RNA. RNA polymerase II (abbreviated RNAP II or RNA Pol II), is the enzyme responsible for transcribing the vast majority of protein-coding genes in eukaryotes. It is also responsible for transcribing the majority of genes encoding short nuclear RNAs (snRNAs) and micro RNAs (miRNAs). As such, RNAP II is the most well-studied and well understood of the eukaryotic RNAPs. Genes transcribed by RNAP II are referred to as "type II genes" and comprise the vast majority of genes present in eukaryotic genomes. RNA polymerase I (RNAP I or RNA Pol I) transcribes most of the ribosomal RNAs in a eukaryotic cell. RNA polymerase III (RNAP III or RNA pol III) transcribes the tRNA precursors, as well ...
The spermatogonial stem cell (SSC), is an adult stem cell capable of both self-renewal and differentiation, thereby playing a critical role in spermatogenesis....
RATIONALE: Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. METHODS: 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. RESULTS: A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B ...
Next Generation Sequencing applications allow biomedical researchers to examine the expression of tens of thousands of genes at once, giving researchers the opportunity to examine expression across entire genomes. RNA Sequencing applications such as Tag Profiling, Small RNA and Whole Transcriptome Analysis can identify and characterize both known and novel transcripts, splice junctions and non-coding RNAs. These sequencing based-applications also allow for the examination of nucleotide variant. Next Generation Sequencing and these RNA applications allow researchers to examine the cancer transcriptome at an unprecedented level. This presentation will provide an overview of the gene expression data analysis process for these applications with an emphasis on identification of differentially expressed genes, identification of novel transcripts and characterization of alternative splicing as well as variant analysis and small RNA expression. Using data drawn from the GEO data repository and the Short ...
Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. LncRNAs have been recently recognized as the hallmark features in various diseases. In hematopoiesis, they regulate development at almost every stage of cell lineage differentiation; therefore, abnormal expression of lncRNAs may lead to different hematopoietic disorders. Until now there has been almost no information available about lncRNA deregulation and role in myelodysplastic syndromes (MDS).. We perform genome-wide screening of lncRNA levels in MDS patients and compare expression profiles between various risk groups of patients and healthy subjects, to find lncRNAs with altered levels in MDS. This knowledge will help us to better understand the pathogenesis of MDS and identify lncRNAs that may represent candidate diagnostic and prognostic molecular markers of the disease.. ...
Caspases are important regulators and executioners in the apoptosis pathways and play crucial roles in carcinogenesis. We tested the hypothesis that functional variants of CASP genes are associated with risk of squamous cell carcinoma of the head and neck (SCCHN) and second primary malignancy (SPM). We genotyped 7 selected, potentially functional single nucleotide polymorphisms (SNPs) located in the microRNA binding sites of the 3 untranslational region (UTR; 2 in CASP3, 1 in CASP6, and 4 in CASP7) and evaluated their associations first with risk of SCCHN in 1066 patients with SCCHN and 1074 cancer-free control subjects and then with SPM in 846 patients in the same non-Hispanic white study population. We found that compared with the CASP3 TT genotype of rs1049253, the variant TC/CC genotypes were associated with significantly increased risk of SCCHN (adjusted odds ratio=1.29 and 95% confidence interval=1.07-1.56) and SPM (adjusted hazard ratio=1.79 and 95% CI=1.02-3.16) and worse SPM-free ...
Adenylosuccinate synthetase isozyme 1  Adenylosuccinate synthetase isozyme 1
This gene encodes a member of the adenylosuccinate synthase family of proteins. The encoded muscle-specific enzyme plays a role ... Recombinant mouse muscle adenylosuccinate synthetase: overexpression, kinetics, and crystal structure.. 1592113. 1992. Cloning ... A novel muscle isozyme of adenylosuccinate synthetase, human AdSSL1, is identified from human bone marrow stromal cells.. ... Molecular cloning and characterization of a novel muscle adenylosuccinate synthetase, AdSSL1, from human bone marrow stromal ...
more infohttps://pharos.nih.gov/idg/targets/Q8N142
Amidophosphoribosyltransferase  Amidophosphoribosyltransferase
Adenylosuccinate Lyase Deficiency 37 Azathioprine Action Pathway 47 Gout or Kelley-Seegmiller Syndrome 37 ... Anthranilate synthase complex 3 Cell 15,807 Cell part 15,807 Cytoplasm 10,353 Cytoplasmic part 7,831 ...
more infohttps://pharos.nih.gov/idg/targets/Q06203
Isozyme Shift of Adenylosuccinate Synthase in Rat and Human Neoplasms | SpringerLink  Isozyme Shift of Adenylosuccinate Synthase in Rat and Human Neoplasms | SpringerLink
Adenylosuccinate synthase (EC 6.3.4.4) catalyzes the first reaction of AMP biosynthesis at IMP branching point. Previous ... Adenylosuccinate synthase (EC 6.3.4.4) catalyzes the first reaction of AMP biosynthesis at IMP branching point. Previous ... separated two isozymes of adenylosuccinate synthase in rat liver and characterized that the acidic isozyme has a lower Km for ... Ikegami T., Natsumeda Y., Weber G. (1989) Isozyme Shift of Adenylosuccinate Synthase in Rat and Human Neoplasms. In: Mikanagi K ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4684-5673-8_68
Adenylosuccinate synthase - Wikipedia  Adenylosuccinate synthase - Wikipedia
Humans express two adenylosuccinate synthase isozymes: Adenylosuccinate synthase at the US National Library of Medicine Medical ... In molecular biology, Adenylosuccinate synthase (or adenylosuccinate synthetase) (EC 6.3.4.4.) is an enzyme that plays an ... Adenylosuccinate synthetase has been characterised from various sources ranging from Escherichia coli (gene purA) to vertebrate ... Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known ...
more infohttps://en.wikipedia.org/wiki/Adenylosuccinate_synthase
Primary antibodies - Page 7 of 481 on u | Genetex Inc.  Primary antibodies - Page 7 of 481 on 'u' | Genetex Inc.
Adenylosuccinate synthase antibody Rabbit Polyclonal Hu, Ms, Rat ICC/IF, IHC-P, WB ...
more infohttp://www.genetex.com/Web/search/Catalog/7?Category=494&Keyword=u
KEGG BRITE: KEGG Orthology (KO) - Cricetulus griseus (Chinese hamster)  KEGG BRITE: KEGG Orthology (KO) - Cricetulus griseus (Chinese hamster)
100767083 Adss; adenylosuccinate synthase 100751825 Adssl1; adenylosuccinate synthase like 1 100689060 Adsl; adenylosuccinate ... adenylosuccinate synthase [EC:6.3.4.4] K01939 purA; adenylosuccinate synthase [EC:6.3.4.4] K01756 purB; adenylosuccinate lyase ... 100758127 Nos1; nitric oxide synthase 1 100760062 Nos2; nitric oxide synthase 2 100769961 Nos3; nitric oxide synthase 3 ... nitric-oxide synthase, brain [EC:1.14.13.39] K13241 NOS2; nitric-oxide synthase, inducible [EC:1.14.13.39] K13242 NOS3; nitric- ...
more infohttp://www.genome.jp/kegg-bin/get_htext?cge00001+100774486
ADE12 | SGD  ADE12 | SGD
Adenylosuccinate synthase involved in purine nucleotide biosynthesis; localized to the cytoplasm, also binds to the DNA ... Adenylosuccinate synthase; catalyzes the first step in synthesis of adenosine monophosphate from inosine 5monophosphate during ...
more infohttps://www.yeastgenome.org/locus/S000005164
KEGG PATHWAY: hsa00230  KEGG PATHWAY: hsa00230
ADSSL1; adenylosuccinate synthase like 1 [KO:K01939] [EC:6.3.4.4]. 159 ADSS; adenylosuccinate synthase [KO:K01939] [EC:6.3.4.4] ... GMPS; guanine monophosphate synthase [KO:K01951] [EC:6.3.5.2]. 2766 GMPR; guanosine monophosphate reductase [KO:K00364] [EC:1.7 ... ADSL; adenylosuccinate lyase [KO:K01756] [EC:4.3.2.2]. 471 ATIC; 5-aminoimidazole-4-carboxamide ribonucleotide ... PFAS; phosphoribosylformylglycinamidine synthase [KO:K01952] [EC:6.3.5.3]. 10606 PAICS; phosphoribosylaminoimidazole ...
more infohttps://www.genome.jp/dbget-bin/www_bget?hsa00230
Principles of Biochemistry/Nucleic acid III: Sythesis of nucleotides - Wikibooks, open books for an open world  Principles of Biochemistry/Nucleic acid III: Sythesis of nucleotides - Wikibooks, open books for an open world
adenylosuccinate synthase converts IMP to adenylosuccinate. *adenylosuccinate lyase converts adenylosuccinate into AMP ... GMP synthase converts XMP into GMP. In enzymology, a GMP synthase (glutamine-hydrolysing) (EC 6.3.5.2) is an enzyme that ... CTPS - CTP synthase 1 CTPS2 - CTP synthase 2 Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid ... CTP synthase. cytidine 5triphosphate(CTP). Glutamine and ATP are used. The first three enzymes are all coded by the same gene ...
more infohttps://en.wikibooks.org/wiki/Principles_of_Biochemistry/Nucleic_acid_III:_Sythesis_of_nucleotides
ADE12 - Adenylosuccinate synthetase - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Bakers yeast) - ADE12 gene &...  ADE12 - Adenylosuccinate synthetase - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) - ADE12 gene &...
adenylosuccinate synthase activity Source: SGD ,p>Inferred from Direct Assay,/p> ,p>Used to indicate a direct assay for the ... "Adenylosuccinate synthase from Saccharomyces cerevisiae: homologous overexpression, purification and characterization of the ... "Adenylosuccinate synthase from Saccharomyces cerevisiae: homologous overexpression, purification and characterization of the ... "Adenylosuccinate synthase from Saccharomyces cerevisiae: homologous overexpression, purification and characterization of the ...
more infohttp://www.uniprot.org/uniprot/P80210
Recombinant Human ADSSL1 protein (ab165184) | Abcam  Recombinant Human ADSSL1 protein (ab165184) | Abcam
Adenylosuccinate synthase like 1. *Adenylosuccinate synthetase. *Adenylosuccinate synthetase isozyme 1. *AdSS 1 ...
more infohttps://www.abcam.com/recombinant-human-adssl1-protein-ab165184.html
ENSDARG00000002071 - Zebrafish Mutation Project - Wellcome Sanger Institute  ENSDARG00000002071 - Zebrafish Mutation Project - Wellcome Sanger Institute
adenylosuccinate synthase [Source:HGNC Symbol;Acc:292]. Mouse Orthologue:. Adss. Mouse Description:. adenylosuccinate ... Adenylosuccinate synthetase isozyme 2 [Source:UniProtKB/Swiss-Prot;Acc:Q568F6]. Human Orthologue:. ADSS. Human Description:. ...
more infohttps://www.sanger.ac.uk/sanger/Zebrafish_Zmpgene/ENSDARG00000002071
purA - Adenylosuccinate synthetase - Haemophilus influenzae (strain PittGG) - purA gene & protein  purA - Adenylosuccinate synthetase - Haemophilus influenzae (strain PittGG) - purA gene & protein
adenylosuccinate synthase activity Source: UniProtKB-UniRule. *GTP binding Source: UniProtKB-UniRule. *magnesium ion binding ... IPR042109 Adenylosuccinate_synth_dom1. IPR042110 Adenylosuccinate_synth_dom2. IPR042111 Adenylosuccinate_synth_dom3. IPR001114 ... IPR042109 Adenylosuccinate_synth_dom1. IPR042110 Adenylosuccinate_synth_dom2. IPR042111 Adenylosuccinate_synth_dom3. IPR001114 ... Adenylosuccinate lyase (CGSHiGG_06455). This subpathway is part of the pathway AMP biosynthesis via de novo pathway, which is ...
more infohttps://www.uniprot.org/uniprot/A5UIZ2
Gene expression profiling of postnatal lung development in the marsupial gray short-tailed opossum ( Monodelphis domestica)...  Gene expression profiling of postnatal lung development in the marsupial gray short-tailed opossum ( Monodelphis domestica)...
Adenylosuccinate synthase like 1. AGER. Advanced glycosylation end-product specific receptor. AKAP5. A-kinase anchoring protein ...
more infohttps://rd.springer.com/article/10.1186%2Fs12864-018-5102-2
SCHLOSSER MYC TARGETS REPRESSED BY SERUM  SCHLOSSER MYC TARGETS REPRESSED BY SERUM
adenylosuccinate synthase. 33247_at. 10213. PSMD14. proteasome (prosome, macropain).... 33332_at. 33394_at. 55308. DDX19A. DEAD ...
more infohttp://software.broadinstitute.org/gsea/msigdb/cards/SCHLOSSER_MYC_TARGETS_REPRESSED_BY_SERUM.html
KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM  KEGG ALANINE ASPARTATE AND GLUTAMATE METABOLISM
carbamoyl-phosphate synthase 1, mitochondrial. 158. 158. ADSL. adenylosuccinate lyase. 159. 159. ADSS. adenylosuccinate ...
more infohttp://software.broadinstitute.org/gsea/msigdb/cards/KEGG_ALANINE_ASPARTATE_AND_GLUTAMATE_METABOLISM.html
adssl1 - PCR Primer Pair - SYBR | PrimePCR | Bio-Rad  adssl1 - PCR Primer Pair - SYBR | PrimePCR | Bio-Rad
Adenylosuccinate synthase like 1. Aliases:. Not Available. RefSeq:. NM_214820. Ensembl:. ENSDARG00000009867 ...
more infohttp://www.bio-rad.com/en-us/prime-pcr-assays/assay/qdrecid0016268-primepcr-sybr-green-assay-adssl1-zebrafish
Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular...  Homocysteine thiolactone and N-homocysteinylated protein induce pro-atherogenic changes in gene expression in human vascular...
Mudd SH et al (1985) The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 37:1- ... Albertini E, Koziel R, Durr A, Neuhaus M, Jansen-Durr P (2012) Cystathionine beta synthase modulates senescence of human ... Zhao JY et al (2012) A functional variant in the cystathionine beta-synthase gene promoter significantly reduces congenital ... Akahoshi N et al (2014) Neutral aminoaciduria in cystathionine beta-synthase-deficient mice; an animal model of homocystinuria ...
more infohttps://rd.springer.com/article/10.1007/s00726-015-1956-7
Human Metabolome Database: Showing metabocard for Inosinic acid (HMDB0000175)  Human Metabolome Database: Showing metabocard for Inosinic acid (HMDB0000175)
2. Adenylosuccinate synthetase isozyme 1. General function:. Involved in adenylosuccinate synthase activity. Specific function: ...
more infohttp://www.hmdb.ca/metabolites/HMDB00175
Human Metabolome Database: Showing metabocard for Adenylsuccinic acid (HMDB0000536)  Human Metabolome Database: Showing metabocard for Adenylsuccinic acid (HMDB0000536)
2. Adenylosuccinate synthetase isozyme 2. General function:. Involved in adenylosuccinate synthase activity. Specific function: ... 3. Adenylosuccinate synthetase isozyme 1. General function:. Involved in adenylosuccinate synthase activity. Specific function: ... 1. Adenylosuccinate lyase. General function:. Involved in catalytic activity. Specific function:. Not Available. Gene Name:. ... parallel deficiency with adenylosuccinate and succinyl-AICAR in profoundly retarded patients and non-parallel deficiency in a ...
more infohttp://www.hmdb.ca/metabolites/HMDB0000536
  • Structures of adenylosuccinate synthetase from Triticum aestivum and Arabidopsis thaliana when compared with the known structures from E. coli reveals that the overall fold is very similar to that of the E. coli protein. (wikipedia.org)