Sample records for human hypoxanthine phosphoribosyltransferase

  1. Human hypoxanthine-guanine phosphoribosyltransferase. Tryptic peptides and post-translational modification of the erythrocyte enzyme.

    PubMed

    Wilson, J M; Landa, L E; Kobayashi, R; Kelley, W N

    1982-12-25

    We describe the isolation and characterization of tryptic peptides of human erythrocyte hypoxanthine-guanine phosphoribosyltransferase. The digest was separated by reverse-phase high pressure liquid chromatography into 30 peaks, 26 of which contained purified peptides. The four complex peaks were resolved by high pressure liquid chromatography with a different reverse-phase column. Each peptide predicted from the recently described amino acid sequence of human erythrocyte hypoxanthine-guanine phosphoribosyltransferase was isolated from this peptide map. Sequence analysis of the purified peptides identified two peptides, 14 and 14d, that differed by an Asn/Asp heterogeneity at the position corresponding to residue 106 of the intact protein. Additional studies indicate that this heterogeneity is due to deamidation of the protein in vivo. This post-translational modification appears to be responsible for some of the electrophoretic heterogeneity observed in the normal erythrocyte enzyme. PMID:7174669

  2. Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase

    PubMed Central

    Clinch, Keith; Crump, Douglas R.; Evans, Gary B.; Hazleton, Keith Z.; Mason, Jennifer M.; Schramm, Vern L.

    2013-01-01

    The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C- nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. PMID:23810424

  3. Crystal structures of free, IMP-, and GMP-bound Escherichia coli hypoxanthine phosphoribosyltransferase

    PubMed Central

    Guddat, Luke W.; Vos, Siska; Martin, Jennifer L.; Keough, Dianne T.; de Jersey, John

    2002-01-01

    Crystal structures have been determined for free Escherichia coli hypoxanthine phosphoribosyltransferase (HPRT) (2.9 ? resolution) and for the enzyme in complex with the reaction products, inosine 5`-monophosphate (IMP) and guanosine 5`-monophosphate (GMP) (2.8 ? resolution). Of the known 6-oxopurine phosphoribosyltransferase (PRTase) structures, E. coli HPRT is most similar in structure to that of Tritrichomonas foetus HGXPRT, with a rmsd for 150 C? atoms of 1.0 ?. Comparison of the free and product bound structures shows that the side chain of Phe156 and the polypeptide backbone in this vicinity move to bind IMP or GMP. A nonproline cis peptide bond, also found in some other 6-oxopurine PRTases, is observed between Leu46 and Arg47 in both the free and complexed structures. For catalysis to occur, the 6-oxopurine PRTases have a requirement for divalent metal ion, usually Mg2+ in vivo. In the free structure, a Mg2+ is coordinated to the side chains of Glu103 and Asp104. This interaction may be important for stabilization of the enzyme before catalysis. E. coli HPRT is unique among the known 6-oxopurine PRTases in that it exhibits a marked preference for hypoxanthine as substrate over both xanthine and guanine. The structures suggest that its substrate specificity is due to the modes of binding of the bases. In E. coli HPRT, the carbonyl oxygen of Asp163 would likely form a hydrogen bond with the 2-exocyclic nitrogen of guanine (in the HPRT-guanine-PRib-PP-Mg2+ complex). However, hypoxanthine does not have a 2-exocyclic atom and the HPRT-IMP structure suggests that hypoxanthine is likely to occupy a different position in the purine-binding pocket. PMID:12070315

  4. Yeast GMP kinase mutants constitutively express AMP biosynthesis genes by phenocopying a hypoxanthine-guanine phosphoribosyltransferase defect.

    PubMed Central

    Lecoq, K; Konrad, M; Daignan-Fornier, B

    2000-01-01

    We have characterized a new locus, BRA3, leading to deregulation of the yeast purine synthesis genes (ADE genes). We show that bra3 mutations are alleles of the GUK1 gene, which encodes GMP kinase. The bra3 mutants have a low GMP kinase activity, excrete purines in the medium, and show vegetative growth defects and resistance to purine base analogs. The bra3 locus also corresponds to the previously described pur5 locus. Several lines of evidence indicate that the decrease in GMP kinase activity in the bra3 mutants results in GMP accumulation and feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), encoded by the HPT1 gene. First, guk1 and hpt1 mutants share several phenotypes, such as adenine derepression, purine excretion, and 8-azaguanine resistance. Second, overexpression of HPT1 allows suppression of the deregulated phenotype of the guk1 mutants. Third, we show that purified yeast HGPRT is inhibited by GMP in vitro. Finally, incorporation of hypoxanthine into nucleotides is similarly diminished in hpt1 and guk1 mutants in vivo. We conclude that the decrease in GMP kinase activity in the guk1 mutants results in deregulation of the ADE gene expression by phenocopying a defect in HGPRT. The possible occurrence of a similar phenomenon in humans is discussed. PMID:11063676

  5. Identification of a single nucleotide change in a mutant gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor)

    Microsoft Academic Search

    Shin Fujimori; Yuji Hidaka; Beverly L. Davidson; Thomas D. Palella; William N. Kelley

    1988-01-01

    HPRTAnn Arbor is a variant of hypoxanthine (guanine) phosphoribosyl-transferase (HPRT: EC 2.4.2.8), which was identified in two brothers with hyperuricemia and nephrolithiasis. In previous studies, this mutant enzyme was characterized by an increased Km for both substrates, a normal Vmax, a decreased intracellular concentration of enzyme protein, a normal subunit molecular weight and an acidic isoelectric point under native isoelectric

  6. Substrate inhibition of adenosine phosphorylation in adenosine deaminase deficiency and adenosine-mediated inhibition of PP-ribose-P dependent nucleotide synthesis in hypoxanthine phosphoribosyltransferase deficient erythrocytes

    Microsoft Academic Search

    F. F. Snyder; C. Dyer; J. E. Seegmiller; R. M. Goldblum; G. C. Mills; F. C. Schmalstieg

    1988-01-01

    Summary The metabolism of adenosine and its effects on phosphoribosylpyrophosphate, PP-ribose-P, dependent nucleotide synthesis were studied using erythrocytes from patients with adenosine deaminase and hypoxanthine phosphoribosyltransferase deficiency as models. The phosphorylation of adenosine was progressively inhibited by concentrations of adenosine greater than 1 µmol L-1 for control and ADA deficient erythrocytes. There was essentially no initial rate of phosphorylation at

  7. Elevated frequencies of hypoxanthine phosphoribosyltransferase lymphocyte mutants are detected in Russian liquidators 6 to 10 years after exposure to radiation from the Chernobyl nuclear power plant accident

    Microsoft Academic Search

    Cynthia B Thomas; David O Nelson; Pavel Pleshanov; Irina Vorobstova; Ludmila Tureva; Ronald Jensen; Irene M Jones

    1999-01-01

    This study was conducted to determine whether the frequency of hypoxanthine phosphoribosyltransferase (HPRT) deficient lymphocyte mutants would detect an effect of radiation exposure in a population of Russians who were exposed to low levels of radiation while working in 1986 and 1987 as liquidators cleaning up after the Chernobyl nuclear power reactor accident. The HPRT lymphocyte cloning assay was performed

  8. Phenotypic Variation Among Seven Members of One Family with Deficiency of Hypoxanthine-Guanine Phosphoribosyltransferase

    PubMed Central

    Ceballos-Picot, Irène; Augé, Franck; Fu, Rong; Olivier-Bandini, Anne; Cahu, Julie; Chabrol, Brigitte; Aral, Bernard; de Martinville, Bérengère; Lecain, Jean-Paul; Jinnah, H. A.

    2013-01-01

    We describe a family of seven boys affected by Lesch-Nyhan disease with various phenotypes. Further investigations revealed a mutation c.203T>C in the gene encoding HGprt of all members, with substitution of leucine to proline at residue 68 (p.Leu68Pro). Thus patients from this family display a wide variety of symptoms although sharing the same mutation. Mutant HGprt enzyme was prepared by site-directed mutagenesis and the kinetics of the enzyme revealed that the catalytic activity of the mutant was reduced, in association with marked reductions in the affinity towards phosphoribosylpyrophosphate (PRPP). Its Km for PRPP was increased 215-fold with hypoxanthine as substrate and 40-fold with guanine as substrate with associated reduced catalytic potential. Molecular modeling confirmed that the most prominent defect was the dramatically reduced affinity towards PRPP. Our studies suggest that the p.Leu68Pro mutation has a strong impact on PRPP binding and on stability of the active conformation. This suggests that factors other than HGprt activity per se may influence the phenotype of Lesch-Nyhan patients. PMID:24075303

  9. Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase.

    PubMed

    Ceballos-Picot, Irène; Augé, Franck; Fu, Rong; Olivier-Bandini, Anne; Cahu, Julie; Chabrol, Brigitte; Aral, Bernard; de Martinville, Bérengère; Lecain, Jean-Paul; Jinnah, H A

    2013-11-01

    We describe a family of seven boys affected by Lesch-Nyhan disease with various phenotypes. Further investigations revealed a mutation c.203T>C in the gene encoding HGprt of all members, with substitution of leucine to proline at residue 68 (p.Leu68Pro). Thus patients from this family display a wide variety of symptoms although sharing the same mutation. Mutant HGprt enzyme was prepared by site-directed mutagenesis and the kinetics of the enzyme revealed that the catalytic activity of the mutant was reduced, in association with marked reductions in the affinity towards phosphoribosylpyrophosphate (PRPP). Its Km for PRPP was increased 215-fold with hypoxanthine as substrate and 40-fold with guanine as substrate with associated reduced catalytic potential. Molecular modeling confirmed that the most prominent defect was the dramatically reduced affinity towards PRPP. Our studies suggest that the p.Leu68Pro mutation has a strong impact on PRPP binding and on stability of the active conformation. This suggests that factors other than HGprt activity per se may influence the phenotype of Lesch-Nyhan patients. PMID:24075303

  10. Engineered delta ribozymes can simultaneously knock down the expression of the genes encoding uracil phosphoribosyltransferase and hypoxanthine–xanthine–guanine phosphoribosyltransferase in Toxoplasma gondii

    Microsoft Academic Search

    J Sheng; F Al-Anouti; S Ananvoranich

    2004-01-01

    Engineered delta ribozymes or HDV ribozymes were used as gene expression modulators in Toxoplasma gondii. The substrate recognition sequence of the trans-acting delta ribozyme, which was derived from the self-cleaving motif located on the antigenomic strand of the hepatitis delta virus genome, was modified to target T. gondii transcripts. The mRNA encoding two well-documented genes, namely uracil phosphoribosyltransferase (UPRT) and

  11. Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

    PubMed

    Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

    2014-09-01

    Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn?HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite. PMID:24923662

  12. Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases*

    PubMed Central

    Zhang, Yong; Evans, Gary B.; Clinch, Keith; Crump, Douglas R.; Harris, Lawrence D.; Fröhlich, Richard F. G.; Tyler, Peter C.; Hazleton, Keith Z.; Cassera, María B.; Schramm, Vern L.

    2013-01-01

    The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nm. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5?-phosphate bound to OPRTs with Kd values near 40 nm. Analogues designed with a C5-pyrimidine carbon–carbon bond to ribocation mimics gave Kd values in the range of 80–500 nm. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5?-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

  13. Transition state analogues of Plasmodium falciparum and human orotate phosphoribosyltransferases.

    PubMed

    Zhang, Yong; Evans, Gary B; Clinch, Keith; Crump, Douglas R; Harris, Lawrence D; Fröhlich, Richard F G; Tyler, Peter C; Hazleton, Keith Z; Cassera, María B; Schramm, Vern L

    2013-11-29

    The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nM. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5'-phosphate bound to OPRTs with Kd values near 40 nM. Analogues designed with a C5-pyrimidine carbon-carbon bond to ribocation mimics gave Kd values in the range of 80-500 nM. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5'-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

  14. Structural complexes of human adenine phosphoribosyltransferase reveal novel features of the APRT catalytic mechanism.

    PubMed

    Silva, Carlos H T P; Silva, Mario; Iulek, Jorge; Thiemann, Otavio H

    2008-06-01

    Adenine phosphoribosyltransferase (APRT) is an important enzyme component of the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida are unable to synthesize purines de novo and use the salvage pathway for the synthesis of purine bases rendering this biosynthetic pathway an attractive target for antiparasitic drug design. The recombinant human adenine phosphoribosyltransferase (hAPRT) structure was resolved in the presence of AMP in the active site to 1.76 A resolution and with the substrates PRPP and adenine simultaneously bound to the catalytic site to 1.83 A resolution. An additional structure was solved containing one subunit of the dimer in the apo-form to 2.10 A resolution. Comparisons of these three hAPRT structures with other 'type I' PRTases revealed several important features of this class of enzymes. Our data indicate that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and PRPP. Comparative analyses presented here provide structural evidence to propose the role of Glu104 as the residue that abstracts the proton of adenine N9 atom before its nucleophilic attack on the PRPP anomeric carbon. This work leads to new insights to the understanding of the APRT catalytic mechanism. PMID:18399692

  15. Pyrophosphate interactions at the transition states of Plasmodium falciparum and human orotate phosphoribosyltransferases.

    PubMed

    Zhang, Yong; Schramm, Vern L

    2010-06-30

    Orotate phosphoribosyltransferases from Plasmodium falciparum and human sources (PfOPRT and HsOPRT) use orotidine as a slow substrate in the pyrophosphorolysis reaction. With orotidine, intrinsic kinetic isotope effects (KIEs) can be measured for pyrophosphorolysis, providing the first use of pyrophosphate (PPi) in solving an enzymatic transition state. Transition-state structures of PfOPRT and HsOPRT were solved through quantum chemical matching of computed and experimental intrinsic KIEs and can be compared to transition states solved with pyrophosphate analogues as slow substrates. PfOPRT and HsOPRT are characterized by late transition states with fully dissociated orotate, well-developed ribocations, and weakly bonded PPi nucleophiles. The leaving orotates are 2.8 A distant from the anomeric carbons at the transition states. Weak participation of the PPi nucleophiles gives C1'-O(PPi) bond distances of approximately 2.3 A. These transition states are characterized by C2'-endo ribosyl pucker, based on the beta-secondary [2'-(3)H] KIEs. The geometry at the 5'-region is similar for both enzymes, with C3'-C4'-C5'-O5' dihedral angles near -170 degrees . These novel phosphoribosyltransferase transition states are similar to but occur earlier in the reaction coordinate than those previously determined with orotidine 5'-monophosphate and phosphonoacetic acid as substrates. The similarity between the transition states with different substrate analogues supports similar transition state structures imposed by PfOPRT and HsOPRT even with distinct reactants. We propose that the transition state similarity with different nucleophiles is determined, in part, by the geometric constraints imposed by the catalytic sites. PMID:20527751

  16. Metabolomics Analysis of Metabolic Effects of Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibition on Human Cancer Cells

    PubMed Central

    Tolstikov, Vladimir; Nikolayev, Alexander; Dong, Sucai; Zhao, Genshi; Kuo, Ming-Shang

    2014-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide–consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry–based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer) and HCT-116 (colorectal cancer) cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA), and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC)-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level. PMID:25486521

  17. GENETIC ASSAY FOR ANEUPLOIDY: QUANTITATION OF CHROMOSOME LOSS USING A MOUSE/HUMAN MONOCHROMOSOMAL HYBRID CELL LINE (JOURNAL VERSION)

    EPA Science Inventory

    A genetic assay is described in which a mouse/human hybrid cell line R3-5 containing a single human chromosome (a monochromosomal hybrid) is used to detect chemically induced aneuploidy. The hybrid cells are deficient in hypoxanthine guanine phosphoribosyltransferase (HGPRT) and ...

  18. Adenoviral-mediated transfer of Escherichia coli uracil phosphoribosyltransferase ( UPRT) gene to modulate the sensitivity of the human colon cancer cells to 5-fluorouracil

    Microsoft Academic Search

    F Koyama; H Sawada; H Fujii; H Hamada; T Hirao; M Ueno; H Nakano

    2000-01-01

    5-Fluorouracil (5-FU) has been used as a chemotherapeutic drug for colorectal cancer. Escherichia coli uracil phosphoribosyltransferase (UPRT), a pyrimidine salvage enzyme, converts 5-FU into 5-fluorouridine monophosphate (5-FUMP) at the initial step of 5-FU activation. We investigated the effects of adenoviral-mediated transfer of the E. coliUPRT gene into human colon cancer cells on 5-FU metabolism and 5-FU chemosensitivity. Three cell lines

  19. DELETION MUTATIONS IN THE HPRT GENE OF T-LYMPHOCYTES AS A BIOMARKER FOR GENOMIC REARRANGEMENTS IMPORTANT IN HUMAN CANCERS

    EPA Science Inventory

    The DNA sequence of 11 in vivo-arising intragenic deletion breaksite junctions occurring in the hypoxanthine guanine phosphoribosyltransferase gene of human T-lymphocytes was determined and deletions ranged in size from 16 bp to 4057 bp. o extensive homology was found at the dele...

  20. MULTIPLEX PCR ANALYSIS OF IN VIVO-ARISING DELETION MUTATIONS IN THE HPRT GENE OF HUMAN T-LYMPHOCYTES

    EPA Science Inventory

    A multiplex polymerase chain reaction (PCR) procedure was adapted for the rapid and efficient evaluation of the hypoxanthine guanine phosphoribosyltransferase (hprt) gene in human T-lymphocytes for deletions. he hprt clonal assay was used to isolate in-vivo-arising hprt-deficient...

  1. Inhibition of Nicotinamide Phosphoribosyltransferase

    PubMed Central

    Pittelli, Maria; Formentini, Laura; Faraco, Giuseppe; Lapucci, Andrea; Rapizzi, Elena; Cialdai, Francesca; Romano, Giovanni; Moneti, Gloriano; Moroni, Flavio; Chiarugi, Alberto

    2010-01-01

    The NAD rescue pathway consists of two enzymatic steps operated by nicotinamide phosphoribosyltransferase (Nampt) and nicotinamide mononucleotide adenylyltransferases. Recently, the potent Nampt inhibitor FK866 has been identified and evaluated in clinical trials against cancer. Yet, how Nampt inhibition affects NAD contents and bioenergetics is in part obscure. It is also unknown whether NAD rescue takes place in mitochondria, and FK866 alters NAD homeostasis within the organelle. Here, we show that FK866-dependent reduction of the NAD contents is paralleled by a concomitant increase of ATP in various cell types, in keeping with ATP utilization for NAD resynthesis. We also show that poly- and mono(ADP-ribose) transferases rather than Sirt-1 are responsible for NAD depletion in HeLa cells exposed to FK866. Mass spectrometry reveals that the drug distributes in the cytosolic and mitochondrial compartment. However, the cytoplasmic but not the mitochondrial NAD pool is reduced upon acute or chronic exposure to the drug. Accordingly, Nampt does not localize within the organelles and their bioenergetics is not affected by the drug. In the mouse, FK866-dependent reduction of NAD contents in various organs is prevented by inhibitors of poly(ADP-ribose) polymerases or the NAD precursor kynurenine. For the first time, our data indicate that mitochondria lack the canonical NAD rescue pathway, broadening current understanding of cellular bioenergetics. PMID:20724478

  2. A survey of splice variants of the human hypoxanthine phosphoribosyl transferase and DNA polymerase beta genes: products of alternative or aberrant splicing?

    PubMed

    Skandalis, Adonis; Uribe, Elke

    2004-01-01

    Errors during the pre-mRNA splicing of metazoan genes can degrade the transmission of genetic information, and have been associated with a variety of human diseases. In order to characterize the mutagenic and pathogenic potential of mis-splicing, we have surveyed and quantified the aberrant splice variants in the human hypoxanthine phosphoribosyl transferase (HPRT) and DNA polymerase beta (POLB) in the presence and the absence of the Nonsense Mediated Decay (NMD) pathway, which removes transcripts with premature termination codons. POLB exhibits a high frequency of splice variants (40-60%), whereas the frequency of HPRT splice variants is considerably lower (approximately 1%). Treatment of cells with emetine to inactivate NMD alters both the spectrum and frequency of splice variants of POLB and HPRT. It is not certain at this point, whether POLB and HPRT splice variants are the result of regulated alternative splicing processes or the result of aberrant splicing, but it appears likely that at least some of the variants are the result of splicing errors. Several mechanisms that may contribute to aberrant splicing are discussed. PMID:15601998

  3. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

    PubMed Central

    Torres, Rosa J; Puig, Juan G

    2007-01-01

    Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent). Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay), and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts) and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15–18 weeks' gestation, or chorionic villus cells obtained at about 10–12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The lack of precise understanding of the neurological dysfunction has precluded development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation, including management of dysarthria and dysphagia, special devices to enable hand control, appropriate walking aids, and a programme of posture management to prevent deformities are recommended. Self-injurious behaviour must be managed by a combination of physical restraints, behavioural and pharmaceutical treatments. PMID:18067674

  4. INDUCTION OF MUTATIONS BY CHEMICAL AGENTS AT THE HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE LOCUS IN HUMAN EPITHELIAL TERATOMA CELLS

    EPA Science Inventory

    Induction of 6-thioguanine (TG) resistance by chemical mutagens was examined in a line of cells derived from a human epithelial teratocarcinoma cell clone. The cells, designated as P3 cells, have a stable diploid karyotype with 46(XX) chromosomes, including a translocation betwee...

  5. Prospects for cellular mutational assays in human populations

    SciTech Connect

    Mendelsohn, M.L.

    1984-06-29

    Practical, sensitive, and effective human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis studies. Such assays would fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. This paper discusses the following possible human cellular assays: (1) HPRT (hypoxanthine phosphoribosyltransferase) somatic cell mutation based on 6-thioguanine resistance; (2) hemoglobin somatic cell mutation assay; (3) glycophorin somatic cell mutation assay; and (4) LDH-X sperm cell mutation assay. 18 references.

  6. Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)\\/pre-B cell colony (PBEF)\\/visfatin linking obesity and inflammation in humans

    Microsoft Academic Search

    D. Friebe; M. Neef; J. Kratzsch; S. Erbs; K. Dittrich; A. Garten; S. Petzold-Quinque; S. Blüher; T. Reinehr; M. Stumvoll; M. Blüher; W. Kiess; A. Körner

    2011-01-01

    Aims\\/hypothesis  Nicotinamide phosphoribosyltransferase (NAMPT) is a multifunctional protein potentially involved in obesity and glucose metabolism.\\u000a We systematically studied the association between circulating NAMPT, obesity, interventions and glucose metabolism and investigated\\u000a potential underlying inflammatory mechanisms.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Fasting morning NAMPT serum levels were measured in cohorts of lean vs obese children, cohorts of intervention by lifestyle,\\u000a exercise and bariatric surgery, and during an OGTT.

  7. Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis

    PubMed Central

    Ceballos-Picot, Irene; Mockel, Lionel; Potier, Marie-Claude; Dauphinot, Luce; Shirley, Thomas L.; Torero-Ibad, Raoul; Fuchs, Julia; Jinnah, H.A.

    2009-01-01

    Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in Lesch-Nyhan disease (LND), where affected individuals exhibit a characteristic neurobehavioral disorder that has been linked with dysfunction of dopaminergic pathways of the basal ganglia. Since the functions of HPRT, a housekeeping enzyme responsible for recycling purines, have no direct relationships with the dopaminergic pathways, the mechanisms whereby HPRT deficiency affect them remain unknown. The current studies demonstrate that HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype, using several different cell models for HPRT deficiency. Microarray methods and quantitative PCR were applied to 10 different HPRT-deficient (HPRT?) sublines derived from the MN9D cell line. Despite the variation inherent in such mutant sublines, several consistent abnormalities were evident. Most notable were increases in the mRNAs for engrailed 1 and 2, transcription factors known to play a key role in the specification and survival of dopamine neurons. The increases in mRNAs were accompanied by increases in engrailed proteins, and restoration of HPRT reverted engrailed expression towards normal levels, demonstrating a functional relationship between HPRT and engrailed. The functional relevance of the abnormal developmental molecular signature of the HPRT? MN9D cells was evident in impoverished neurite outgrowth when the cells were forced to differentiate chemically. To verify that these abnormalities were not idiosyncratic to the MN9D line, HPRT? sublines from the SK-N-BE(2) M17 human neuroblastoma line were evaluated and an increased expression of engrailed mRNAs was also seen. Over-expression of engrailed occurred even in primary fibroblasts from patients with LND in a manner that suggested a correlation with disease severity. These results provide novel evidence that HPRT deficiency may affect dopaminergic neurons by influencing early developmental mechanisms. PMID:19342420

  8. Interactions at the Dimer Interface Influence the Relative Efficiencies for Purine Nucleotide Synthesis and Pyrophosphorolysis in a Phosphoribosyltransferase

    SciTech Connect

    Canyuk, Bhutorn; Medrano, Francisco J.; Wenck, MaryAnne; Focia, Pamela J.; Eakin, Ann E.; Craig III, Sydney P. (UNC); (Connecticut)

    2010-03-05

    Enzymes that salvage 6-oxopurines, including hypoxanthine phosphoribosyltransferases (HPRTs), are potential targets for drugs in the treatment of diseases caused by protozoan parasites. For this reason, a number of high-resolution X-ray crystal structures of the HPRTs from protozoa have been reported. Although these structures did not reveal why HPRTs need to form dimers for catalysis, they revealed the existence of potentially relevant interactions involving residues in a loop of amino acid residues adjacent to the dimer interface, but the contributions of these interactions to catalysis remained poorly understood. The loop, referred to as active-site loop I, contains an unusual non-proline cis-peptide and is composed of residues that are structurally analogous with Leu67, Lys68, and Gly69 in the human HPRT. Functional analyses of site-directed mutations (K68D, K68E, K68N, K68P, and K68R) in the HPRT from Trypanosoma cruzi, etiologic agent of Chagas disease, show that the side-chain at position 68 can differentially influence the K{sub m} values for all four substrates as well as the k{sub cat} values for both IMP formation and pyrophosphorolysis. Also, the results for the K68P mutant are inconsistent with a cis-trans peptide isomerization-assisted catalytic mechanism. These data, together with the results of structural studies of the K68R mutant, reveal that the side-chain of residue 68 does not participate directly in reaction chemistry, but it strongly influences the relative efficiencies for IMP formation and pyrophosphorolysis, and the prevalence of lysine at position 68 in the HPRT of the majority of eukaryotes is consistent with there being a biological role for nucleotide pyrophosphorolysis.

  9. Regulation of hypoxanthine transport in Neurospora crassa

    E-print Network

    Sabina, Richard Lee

    1976-01-01

    the adenine auxotrophic strains, ad-l, ad-8, and the double mutant strain, ad-1;ad-8. Normal (or wild-type) hypoxanthine transport capacity was found in the ad-1 conidia, whereas the ad-8 strain failed to take up any hypoxanthine. The double mutant strains... showed intermediate transport capacities. Similar results were obtained for IMP:pyrophosphorylase activity as- sayed in germinated conidia, The ad-1 strain showed greatest activ- ity, the ad-8 strain showed the least activity, and the double mutant...

  10. In vivo footprint analysis and genomic sequencing of the human hypoxanthine-phosphoribosyl transferase (HPRT) 5 prime region on the active and inactive X chromosome

    SciTech Connect

    Hornstra, I.K.; Yang, T.P. (Univ. of Florida, Gainesville (United States))

    1991-03-11

    In female placental mammals, one of the two X chromosome in each somatic cell is randomly inactivated during female embryogenesis as a mechanism for dosage compensation. Once a given X chromosome is inactivated, all mitotic progeny maintain the same X chromosome in the inactive state. DNA-protein interactions and DNA methylation are hypothesized to maintain this allele-specific system of differential gene expression. Ligation-mediated polymerase chain reaction (LMPCR) in vivo footprinting and genomic sequencing were used to study DNA-protein interactions and DNA-methylation within the 5{prime} region of the X-linked human HPRT gene on the active and inactive X chromosomes. In vivo footprint analysis reveals at least one DNA-protein interaction specific to the active HPRT allele in human male fibroblast cells and hamster-human hybrid cells containing only the active human X chromosome. In the region examined, all CpG dinucleotides are methylated on the inactive HPRT allele and unmethylated on the active X allele in hamster-human hybrid cells carrying either the inactive or active human X chromosome, respectively. Thus, DNA-methylation may be mediating the differential binding of sequence-specific DNA-binding proteins to the active or inactive HPRT alleles.

  11. Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

    PubMed Central

    Mateos, F A; Puig, J G; Jiménez, M L; Fox, I H

    1987-01-01

    We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria. PMID:3818951

  12. Regulation of hypoxanthine phosphoribosyltransferase, glyceraldehyde?3?phosphate dehydrogenase and ??actin mRNA expression in porcine immune cells and tissues

    Microsoft Academic Search

    Dennis L. Foss; Mary Jo Baarsch; Michael P. Murtaugh

    1998-01-01

    Various “housekeeping” genes are often used as endogenous controls in gene expression experiments. We have cloned from swine, three genes commonly used as endogenous controls in other species and have characterized their relative levels of expression in various porcine tissues and their response to various cell activators. Glyceraldehyde?3?phosphate dehydrogenase (GAPDH) and ??actin were readily detected by northern hybridization in various

  13. V(D)J RECOMBINASE-MEDIATED DELETION OF THE HPRT GENE IN T-LYMPHOCYTES FROM ADULT HUMANS

    EPA Science Inventory

    The hprt T-cell cloning assay allows the detection of mutations occurring in vivo in the hypoxanthine guanine phosphoribosyltransferase (hprt) gene of T-lymphocytes. e have shown previously that the illegitimate activity of V(D)J recombinase accounts for about 40% of the hprt mut...

  14. Adenine phosphoribosyltransferase (APRT) deficiency: identification of a novel nonsense mutation

    PubMed Central

    2014-01-01

    Background Adenine phosphoribosyltransferase deficiency (APRTD) is an under estimated genetic form of kidney stones and/or kidney failure, characterized by intratubular precipitation of 2,8-dihydroxyadenine crystals (2,8-DHA). Currently, five pathologic allelic variants have been identified as responsible of the complete inactivation of APRT protein. Case presentation In this study, we report a novel nonsense mutation of the APRT gene from a 47- year old Italian patient. The mutation, localized in the exon 5, leads to the replacement of a cytosine with a thymine (g.2098C?>?T), introducing a stop codon at amino acid position 147 (p.Gln147X). This early termination was deleterious for the enzyme structural and functional integrity, as demonstrated by the structure analysis and the activity assay of the mutant APRT protein. Conclusion These data revealed that the p.Gln147X mutation in APRT gene might be a new cause of APRT disease. PMID:24986359

  15. Properties of Pea Seedling Uracil Phosphoribosyltransferase and Its Distribution in Other Plants 1

    PubMed Central

    Bressan, Ray A.; Murray, Michael G.; Gale, James M.; Ross, Cleon W.

    1978-01-01

    A uracil phosphoribosyltransferase (UMP-pyrophosphorylase) was found in several angiosperms and was partially purified from epicotyls of pea (Pisum sativum L. cv. Alaska) seedlings. Its pH optimum was about 8.5; its required approximately 0.3 mm MgCl2 for maximum activity but was inhibited by MnCl2; its molecular weight determined by chromatography on Sephadex G-150 columns was approximately 100,000; its Km values for uracil and 5-phosphorylribose 1-pyrophosphate were 0.7 ?m and 11 ?m; and it was partially resolved from a similar phosphoribosyltransferase converting orotic acid to orotodine 5?-phosphate. Enzyme fractions containing both uracil phosphoribosyl transferase and orotate phosphoribosyltransferase converted 6-azauracil and 5-fluorouracil to products with chromatographic properties of 6-azauradine 5?-phosphate and 5-fluorouridine 5?-phosphate. Uracil phosphoribosyltransferase probably functions in salvage of uracil for synthesis of pyrimidine nucleotides. PMID:16660311

  16. Biochemical Characterization of Uracil Phosphoribosyltransferase from Mycobacterium tuberculosis

    PubMed Central

    Villela, Anne Drumond; Ducati, Rodrigo Gay; Rosado, Leonardo Astolfi; Bloch, Carlos Junior; Prates, Maura Vianna; Gonçalves, Danieli Cristina; Ramos, Carlos Henrique Inacio; Basso, Luiz Augusto; Santos, Diogenes Santiago

    2013-01-01

    Uracil phosphoribosyltransferase (UPRT) catalyzes the conversion of uracil and 5-phosphoribosyl-?-1-pyrophosphate (PRPP) to uridine 5?-monophosphate (UMP) and pyrophosphate (PPi). UPRT plays an important role in the pyrimidine salvage pathway since UMP is a common precursor of all pyrimidine nucleotides. Here we describe cloning, expression and purification to homogeneity of upp-encoded UPRT from Mycobacterium tuberculosis (MtUPRT). Mass spectrometry and N-terminal amino acid sequencing unambiguously identified the homogeneous protein as MtUPRT. Analytical ultracentrifugation showed that native MtUPRT follows a monomer-tetramer association model. MtUPRT is specific for uracil. GTP is not a modulator of MtUPRT ativity. MtUPRT was not significantly activated or inhibited by ATP, UTP, and CTP. Initial velocity and isothermal titration calorimetry studies suggest that catalysis follows a sequential ordered mechanism, in which PRPP binding is followed by uracil, and PPi product is released first followed by UMP. The pH-rate profiles indicated that groups with pK values of 5.7 and 8.1 are important for catalysis, and a group with a pK value of 9.5 is involved in PRPP binding. The results here described provide a solid foundation on which to base upp gene knockout aiming at the development of strategies to prevent tuberculosis. PMID:23424660

  17. Insight into the roles of hypoxanthine and thydimine on cultivating antibody-producing CHO cells: cell growth, antibody production and long-term stability

    Microsoft Academic Search

    Fei Chen; Li Fan; Jiaqi Wang; Yan Zhou; Zhaoyang Ye; Liang Zhao; Wen-Song Tan

    The potential of hypoxanthine and thymidine (H&T) to promote growth of CHO cells and production of monoclonal antibody (mAb)\\u000a was explored in this study. It was demonstrated that H&T stimulated the initial cell growth and enhanced volumetric production\\u000a of anti-human CD20 mAb by 22%, mainly through the elevated integrated viable cell concentration (IVCC). The moderate alteration\\u000a in cell cycle distribution

  18. Nicotinamide phosphoribosyltransferase (NAMPT) activity is essential for survival of resting lymphocytes.

    PubMed

    Pittelli, Maria; Cavone, Leonardo; Lapucci, Andrea; Oteri, Claudia; Felici, Roberta; Niccolai, Elena; Amedei, Amedeo; Chiarugi, Alberto

    2014-02-01

    NAD biosynthesis is emerging as a key regulator of immune cell functions. Accordingly, inhibitors of the NAD-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT) have anti-inflammatory effects, counteract hematological malignancies and are being tested in clinical trials. Still, their effect on different cell types still waits to be fully investigated. Here we show that the NAMPT inhibitor FK866 induces NAD depletion in various mouse organs but selectively causes dramatic atrophy of the spleen red pulp. Accordingly, in cultured mouse lymphocytes exposed to FK866, NAD contents drop to 50% of basal values within 2 days, a condition sufficient to prompt complete cell death. Cultures of human lymphocytes are more resistant to FK866 and sustain a 50% NAD reduction for 5 days before dying. Death of both cell types can be prevented by different NAD precursors, indicating critical NAD homeostasis in lymphocytes. Indeed, inhibition of the NAD-consuming enzyme poly(ADP-ribose) polimerase-1 suffices to prevent FK866-induced NAD depletion and death of both lymphocyte types. Poly(ADP-ribose) polymerase-1-null lymphocytes also undergo lower NAD depletion and reduced cell death when exposed to the drug. At variance with other cell types, neither apoptosis nor autophagy are exclusively responsible for lymphocyte death by FK866, consistent with a general impairment of lymphocyte homeostasis following NAD depletion. Data demonstrate a unique sensitivity of resting lymphocytes to NAD-depleting agents, providing new hints of relevance to lymphocyte biology and therapeutic interventions with NAMPT inhibitors. PMID:24275857

  19. Prognostic value of serum nicotinamide phosphoribosyltransferase in patients with bladder cancer

    PubMed Central

    Zhang, Kui; Zhou, Bin; Zhang, Peng; Zhang, Zhu; Chen, Peng; Pu, Yan; Song, Yaping; Zhang, Lin

    2014-01-01

    Aim To analyze the serum nicotinamide phosphoribosyltransferase (Nampt) level and its prognostic value in bladder cancer (BC). Methods The study included 131 patients with transitional cell BC and 109 healthy controls from the West China Hospital of Sichuan University in the period between 2007 and 2013. Nampt concentration in serum was measured by commercial ELISA kits for human Nampt. Results The serum Nampt protein level in patients with BC (mean?±?standard deviation, 16.02?±?7.95 ng/mL) was significantly higher than in the control group (6.46?±?2.08 ng/mL) (P?14.74 ng/mL) indicating shorter recurrence-free survival rate (hazard ratio?=?2.85, 95% confidence interval, 1.01-8.06; P?=?0.048). Conclusion Our results suggest that serum Nampt level may serve as a biomarker of BC and an independent prognostic marker of non-muscle-invasive BC. PMID:25358883

  20. Preparation and screening of an arrayed human genomic library generated with the P1 cloning system.

    PubMed Central

    Shepherd, N S; Pfrogner, B D; Coulby, J N; Ackerman, S L; Vaidyanathan, G; Sauer, R H; Balkenhol, T C; Sternberg, N

    1994-01-01

    We describe here the construction and initial characterization of a 3-fold coverage genomic library of the human haploid genome that was prepared using the bacteriophage P1 cloning system. The cloned DNA inserts were produced by size fractionation of a Sau3AI partial digest of high molecular weight genomic DNA isolated from primary cells of human foreskin fibroblasts. The inserts were cloned into the pAd10sacBII vector and packaged in vitro into P1 phage. These were used to generate recombinant bacterial clones, each of which was picked robotically from an agar plate into a well of a 96-well microtiter dish, grown overnight, and stored at -70 degrees C. The resulting library, designated DMPC-HFF#1 series A, consists of approximately 130,000-140,000 recombinant clones that were stored in 1500 microtiter dishes. To screen the library, clones were combined in a pooling strategy and specific loci were identified by PCR analysis. On average, the library contains two or three different clones for each locus screened. To date we have identified a total of 17 clones containing the hypoxanthine-guanine phosphoribosyltransferase, human serum albumin-human alpha-fetoprotein, p53, cyclooxygenase I, human apurinic endonuclease, beta-polymerase, and DNA ligase I genes. The cloned inserts average 80 kb in size and range from 70 to 95 kb, with one 49-kb insert and one 62-kb insert. Images PMID:8146166

  1. A novel human artificial chromosome gene expression system using herpes simplex virus type 1 vectors

    PubMed Central

    Moralli, Daniela; Simpson, Kirsty M; Wade-Martins, Richard; Monaco, Zoia Larin

    2006-01-01

    Human artificial chromosome (HAC) vectors are an important gene transfer system for expression and complementation studies. We describe a significant advance in HAC technology using infectious herpes simplex virus type 1 (HSV-1) amplicon vectors for delivery. This highly efficient method has allowed gene-expressing HACs to be established in glioma-, kidney- and lung-derived cells. We also developed an HSV-1 hypoxanthine phosphoribosyltransferase (HPRT) HAC vector, which generated functional HPRT-expressing HACs that complemented the genetic deficiency in human cells. The transduction efficiency of the HSV-1 HAC amplicons is several orders of magnitude higher than lipofection-mediated delivery. Studies on HAC stability between cell types showed important differences that have implications for HAC development and gene expression in human cells. This is the first report of establishing gene-expressing HACs in human cells by using an efficient, high-capacity viral vector and by identifying factors that are involved in cell-type-specific HAC instability. The work is a significant advance for HAC technology and the development of HAC gene expression systems in human cells. PMID:16906131

  2. Nicotinamide phosphoribosyltransferase can affect metastatic activity and cell adhesive functions by regulating integrins in breast cancer.

    PubMed

    Santidrian, Antonio F; LeBoeuf, Sarah E; Wold, Erik D; Ritland, Melissa; Forsyth, Jane S; Felding, Brunhilde H

    2014-11-01

    NAD(+) metabolism is an essential regulator of cellular redox reactions, energy pathways, and a substrate provider for NAD(+) consuming enzymes. We recently demonstrated that enhancement of NAD(+)/NADH levels in breast cancer cells with impaired mitochondrial NADH dehydrogenase activity, through augmentation of complex I or by supplementing tumor cell nutrients with NAD(+) precursors, inhibits tumorigenicity and metastasis. To more fully understand how aberrantly low NAD(+) levels promote tumor cell dissemination, we here asked whether inhibition of NAD(+) salvage pathway activity by reduction in nicotinamide phosphoribosyltransferase (NAMPT) expression can impact metastasis and tumor cell adhesive functions. We show that knockdown of NAMPT, the enzyme catalyzing the rate-limiting step of the NAD(+) salvage pathway, enhances metastatic aggressiveness in human breast cancer cells and involves modulation of integrin expression and function. Reduction in NAMPT expression is associated with upregulation of select adhesion receptors, particularly ?v?3 and ?1 integrins, and results in increased breast cancer cell attachment to extracellular matrix proteins, a key function in tumor cell dissemination. Interestingly, NAMPT downregulation prompts expression of integrin ?v?3 in a high affinity conformation, known to promote tumor cell adhesive interactions during hematogenous metastasis. NAMPT has been selected as a therapeutic target for cancer therapy based on the essential functions of this enzyme in NAD(+) metabolism, cellular redox, DNA repair and energy pathways. Notably, our results indicate that incomplete inhibition of NAMPT, which impedes NAD(+) metabolism but does not kill a tumor cell can alter its phenotype to be more aggressive and metastatic. This phenomenon could promote cancer recurrence, even if NAMPT inhibition initially reduces tumor growth. PMID:25263164

  3. Analysis of the structural integrity of YACs comprising human immunoglobulin genes in yeast and in embryonic stem cells

    SciTech Connect

    Mendez, M.J.; Abderrahim, H.; Noguchi, M. [Cell Genesys, Inc., Foster City, CA (United States)] [and others] [Cell Genesys, Inc., Foster City, CA (United States); and others

    1995-03-20

    With the goal of creating a strain of mice capable of producing human antibodies, we are cloning and reconstructing the human immunoglobulin germline repertoire in yeast artificial chromosomes (YACs). We describe the identification of YACs containing variable and constant region sequences from the human heavy chain (IgH) and kappa light chain (IgK) loci and the characterization of their integrity in yeast and in mouse embryonic stem (ES) cells. The IgH locus-derived YAC contains five variable (V{sub H}) genes, the major diversity (D) gene cluster, the joining (J{sub H}) genes, the intronic enhancer (E{sub H}), and the constant region genes, mu (C{mu}) and delta (C{delta}). Two IgK locus-derived YACs each contain three variable (V{kappa}) genes, the joining (J{kappa}) region, the intronic enhancer (E{kappa}), the constant gene (C{kappa}), and the kappa deleting element (kde). The IgH YAC was unstable in yeast, generating a variety of deletion derivatives, whereas both IgK YACs were stable. YACs encoding heavy chain and kappa light chain, retrofitted with the mammalian selectable marker, hypoxanthine phosphoribosyltransferase (HPRT), were each introduced into HPRT-deficient mouse ES cells. Analysis of YAC integrity in ES cell lines revealed that the majority of DNA inserts were integrated in substantially intact form. 78 refs., 7 figs.

  4. Flow-injection analysis for hypoxanthine in meat with dissolved oxygen detector and enzyme reactor.

    PubMed

    Numata, M; Funazaki, N; Ito, S; Asano, Y; Yano, Y

    1996-12-01

    A low cost flow-injection analysis (FIA) with a dissolved oxygen (DO) detector and a xanthine oxidase immobilized column for the analysis of hypoxanthine as an index to determine degree of aging in meat was developed for quality control in the food industry. In this system, hypoxanthine is oxidized by an enzyme reaction with xanthine oxidase immobilized on the column to produce xanthine. Then the catalytic reaction between hypoxanthine and DO with xanthine oxidase proceeds with the DO concentration decreasing in the stream of the flow system. Decrease in the DO concentration was monitored by a DO detector located downstream of the flow system. This decrease in DO concentration was proportional to the hypoxanthine concentration. For detecting the decreased DO concentration efficiently a flow-through cell with a polarographic-type DO sensor was specially designed. As a result, a linear working curve was obtained from 3.68 x 10(-5) to 1.84 x 10(-3) M hypoxanthine concentrations with this FIA system. We applied the present system with a DO detector for the determination of hypoxanthine in meat samples and compared the results with those obtained by the conventional HPLC method. The data obtained with the present FIA method were in fairly good agreement with those obtained by the conventional HPLC method for the meat samples. Correlation factor and regression line between the two methods were 0.998 and Y= 1.51X-32.64 respectively. We concluded that the present FIA system with a DO detector was suitable as a simple, easy to handle and reliable instrument for quality control in the food industry. PMID:18966697

  5. The effect of nitroglycerin on myocardial release of inosine, hypoxanthine and lactate during pacing-induced angina

    Microsoft Academic Search

    G. Kugler

    1978-01-01

    Summary The efficacy of nitroglycerin as an antianginal drug has been evaluated by calculation of myocardial extraction and production values of lactate and the adenosine triphosphate (ATP) catabolites inosine and hypoxanthine. Coronary venous and arterial blood was sampled at rest, during pacing-induced angina and 4–6 min after nitroglycerin at identical paced heart rates for enzymatic assay of inosine and hypoxanthine

  6. Hypoxanthine-DNA glycosylase from Escherichia coli. Partial purification and properties.

    PubMed

    Harosh, I; Sperling, J

    1988-03-01

    Hypoxanthine-DNA glycosylase from Escherichia coli was partially purified by ammonium sulfate fractionation and by chromatography on Sephacryl S-200, DEAE-cellulose, and phosphocellulose P-11 columns. Analysis of the enzymatic reaction products was carried out on a minicolumn of DEAE-cellulose and/or by paper chromatography, by following the release of the free base [3H]hypoxanthine from [3H]dIMP-containing phi X174 DNA. In native conditions, the enzyme has a molecular mass of 60 +/- 4 kDa, as determined by gel filtration on Sephadex G-150 and Sephacryl S-200 columns. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed a major polypeptide band of an apparent molecular mass of 56 kDa, and glycerol gradient centrifugation indicated a sedimentation coefficient of 4.0 S. Hypoxanthine-DNA glycosylase from E. coli has an obligatory requirement for Mg2+ and is totally inhibited in the presence of EDTA. Co2+ can only partially replace Mg2+. The enzyme is inhibited by hypoxanthine which at 4 mM causes 85% inhibition. The optimal pH range of the enzymatic activity is 5.5-7.8, and the apparent Km value is 2.5 x 10(-7) M. PMID:2963824

  7. [Catalytic spectrophotometric quantitation for hypoxanthine by conjugating xanthine oxidase with horseradish peroxidase].

    PubMed

    Li, Zhong-qin; Xu, Xiao-ping; Wang, Wu

    2008-09-01

    A novel technology to determine the concentration of hypoxanthine through the chromogenic reaction of phenic acid (PA), 4-aminoantipyrine (AAP) and hydrogen peroxide (H2O2), which was produced via the oxidation of hypoxanthine catalyzed by xanthine oxidase (XO), under the help of horseradish peroxidase (HRP) was proposed in the present paper, according to the reaction of molybdoenzyme xanthine oxidase (XOD, EC 1.2.3.22) which mainly catalyzes the conversion of hypoxanthine and xanthine to xanthine and uric acid, respectively, and is capable of reducing oxygen to generate the reactive oxygen species (ROS), superoxide and hydrogen peroxide. The influences of temperature and pH on the system were investigated. The optimal conditions to determine the concentration of hypoxanthine were obtained as follows: XO (0.32 U x mL(-1)), HRP (7.0 U x mL(-1)), 4-Aminoantipyrine (1 mmol x L(-1)), and phenic acid (6 mmol x L(-1)) were dissolved in 100 mmol x L(-1) Tris-HCl buffer solution (pH 8.3), and the reaction system was incubated in thermostat of 37 degrees C for 8 min, the absorptive wave length was 508 nm. Under the conditions mentioned above, the linear range of calibration curve was between 0.2 and 3.0 mmol x L(-1), the correlation coefficient was 0.9979, and the limit of detection was 0.05 mmol x L(-1). All these show that this technology is a potential alternative method to determine the concentration of hypoxanthine in areas like for example in laboratory or clinical serum diagnosis. PMID:19093586

  8. Nicotinamide phosphoribosyltransferase promotes epithelial-to-mesenchymal transition as a soluble factor independent of its enzymatic activity.

    PubMed

    Soncini, Debora; Caffa, Irene; Zoppoli, Gabriele; Cea, Michele; Cagnetta, Antonia; Passalacqua, Mario; Mastracci, Luca; Boero, Silvia; Montecucco, Fabrizio; Sociali, Giovanna; Lasigliè, Denise; Damonte, Patrizia; Grozio, Alessia; Mannino, Elena; Poggi, Alessandro; D'Agostino, Vito G; Monacelli, Fiammetta; Provenzani, Alessandro; Odetti, Patrizio; Ballestrero, Alberto; Bruzzone, Santina; Nencioni, Alessio

    2014-12-01

    Boosting NAD(+) biosynthesis with NAD(+) intermediates has been proposed as a strategy for preventing and treating age-associated diseases, including cancer. However, concerns in this area were raised by observations that nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in mammalian NAD(+) biosynthesis, is frequently up-regulated in human malignancies, including breast cancer, suggesting possible protumorigenic effects for this protein. We addressed this issue by studying NAMPT expression and function in human breast cancer in vivo and in vitro. Our data indicate that high NAMPT levels are associated with aggressive pathological and molecular features, such as estrogen receptor negativity as well as HER2-enriched and basal-like PAM50 phenotypes. Consistent with these findings, we found that NAMPT overexpression in mammary epithelial cells induced epithelial-to-mesenchymal transition, a morphological and functional switch that confers cancer cells an increased metastatic potential. However, importantly, NAMPT-induced epithelial-to-mesenchymal transition was found to be independent of NAMPT enzymatic activity and of the NAMPT product nicotinamide mononucleotide. Instead, it was mediated by secreted NAMPT through its ability to activate the TGF? signaling pathway via increased TGF?1 production. These findings have implications for the design of therapeutic strategies exploiting NAD(+) biosynthesis via NAMPT in aging and cancer and also suggest the potential of anticancer agents designed to specifically neutralize extracellular NAMPT. Notably, because high levels of circulating NAMPT are found in obese and diabetic patients, our data could also explain the increased predisposition to cancer of these subjects. PMID:25331943

  9. Targeted disruption of the mouse adenine phosphoribosyltransferase (aprt) gene and the production of APRT-deficient mice

    SciTech Connect

    Engle, S.J.; Chen, J.; Tischfield, J.A. [Indiana Univ., School of Medicine, Indianapolis, IN (United States)] [and others

    1994-09-01

    Adenine phosphoribosyltransferase (APRT: EC 2.4.2.7), a ubiquitously expressed purine salvage enzyme, catalyzes the synthesis of AMP and inorganic pyrophosphate from existing adenine and 5-phosphoribosyl-1-pyrophosphate. Deficiency of this enzyme in humans results in the accumulation of 2,8-dihydroxyadenine leading to crystalluria and nephrolithiasis. In order to facilitate our study of this rare, autosomal recessive disorder, we applied the advances in gene targeting technology and mouse embryonic stem (ES) cell culture to the production of APRT-deficient mice. A positive-negative targeting strategy was used. The tageting vector contain 5.6 kb of the mouse APRT gene, a neomycin resistance gene in exon 3 as a positive selection marker, and a HSV thymidine kinase gene at the 3{prime} end of the homology as a negative selection marker. The vector was introduced into D3 ES cells by electroporation and the cells were selected for G418 and ganciclovir (GANC) resistance. G418-GANC resistant clones were screened by Southern blot. One of several correctly targeted clones was expanded and used for blastocyst microinjection to produce chimeric mice. Chimeric animals were bred and agouti progeny heterozygous for the targeted allele were obtained. Heterozygous animals have been bred to produce APRT-deficient animals. Matings are currently underway to determine the phenotype of APRT/HPRT-deficient animals.

  10. Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA

    E-print Network

    Pang, Bo

    Deamination of nucleobases in DNA and RNA results in the formation of xanthine (X), hypoxanthine (I), oxanine, and uracil, all of which are miscoding and mutagenic in DNA and can interfere with RNA editing and function. ...

  11. Thirdhand smoke causes DNA damage in human cells

    PubMed Central

    Hang, Bo

    2013-01-01

    Exposure to thirdhand smoke (THS) is a newly described health risk. Evidence supports its widespread presence in indoor environments. However, its genotoxic potential, a critical aspect in risk assessment, is virtually untested. An important characteristic of THS is its ability to undergo chemical transformations during aging periods, as demonstrated in a recent study showing that sorbed nicotine reacts with the indoor pollutant nitrous acid (HONO) to form tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The goal of this study was to assess the genotoxicity of THS in human cell lines using two in vitro assays. THS was generated in laboratory systems that simulated short (acute)- and long (chronic)-term exposures. Analysis by liquid chromatography–tandem mass spectrometry quantified TSNAs and common tobacco alkaloids in extracts of THS that had sorbed onto cellulose substrates. Exposure of human HepG2 cells to either acute or chronic THS for 24h resulted in significant increases in DNA strand breaks in the alkaline Comet assay. Cell cultures exposed to NNA alone showed significantly higher levels of DNA damage in the same assay. NNA is absent in freshly emitted secondhand smoke, but it is the main TSNA formed in THS when nicotine reacts with HONO long after smoking takes place. The long amplicon–quantitative PCR assay quantified significantly higher levels of oxidative DNA damage in hypoxanthine phosphoribosyltransferase 1 (HPRT) and polymerase ? (POLB) genes of cultured human cells exposed to chronic THS for 24h compared with untreated cells, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity. The findings of this study demonstrate for the first time that exposure to THS is genotoxic in human cell lines. PMID:23462851

  12. Genetic Regulation of Charged Particle Mutagenesis in Human Cells

    NASA Technical Reports Server (NTRS)

    Kronenberg, Amy; Gauny, S.; Cherbonnel-Lasserre, C.; Liu, W.; Wiese, C.

    1999-01-01

    Our studies use a series of syngeneic, and where possible, isogenic human B-lymphoblastoid cell lines to assess the genetic factors that modulate susceptibility apoptosis and their impact on the mutagenic risks of low fluence exposures to 1 GeV Fe ions and 55 MeV protons. These ions are representative of the types of charged particle radiation that are of particular significance for human health in the space radiation environment. The model system employs cell lines derived from the male donor WIL-2. These cells have a single X chromosome and they are hemizygous for one mutation marker, hypoxanthine phosphoribosyltransferase (HPRT). TK6 and WTK1 cells were each derived from descendants of WIL-2 and were each selected as heterozygotes for a second mutation marker, the thymidine kinase (TK) gene located on chromosome 17q. The HPRT and TK loci can detect many different types of mutations, from single basepair substitutions up to large scale loss of heterozygosity (LOH). The single expressing copy of TK in the TK6 and WTKI cell lines is found on the same copy of chromosome 17, and this allele can be identified by a restriction fragment length polymorphism (RFLP) identified when high molecular weight DNA is digested by the SacI restriction endonuclease and hybridized against the cDNA probe for TK. A large series of polymorphic linked markers has been identified that span more than 60 cM of DNA (approx. 60 megabasepairs) and distinguish the copy of chromosome 17 bearing the initially active TK allele from the copy of chromosome 17 bearing the silent TK allele in both TK6 and WTKI cells. TK6 cells express normal p53 protein while WTKI cells express homozygous mutant p53. Expression of mutant p53 can increase susceptibility to x-ray-induced mutations. It's been suggested that the increased mutagenesis in p53 mutant cells might be due to reduced apoptosis.

  13. Mutagenesis in human cells with accelerated H and Fe ions

    NASA Technical Reports Server (NTRS)

    Kronenberg, Amy

    1994-01-01

    The overall goals of this research were to determine the risks of mutation induction and the spectra of mutations induced by energetic protons and iron ions at two loci in human lymphoid cells. During the three year grant period the research has focused in three major areas: (1) the acquisition of sufficient statistics for human TK6 cell mutation experiments using Fe ions (400 MeV/amu), Fe ions (600 MeV/amu) and protons (250 MeV/amu); (2) collection of thymidine kinase- deficient (tk) mutants or hypoxanthine phosphoribosyltransferase deficient (hprt) mutants induced by either Fe 400 MeV/amu, Fe 600 MeV/amu, or H 250 MeV/amu for subsequent molecular analysis; and (3) molecular characterization of mutants isolated after exposure to Fe ions (600 MeV/amu). As a result of the shutdown of the BEVALAC heavy ion accelerator in December 1992, efforts were rearranged somewhat in time to complete our dose-response studies and to complete mutant collections in particular for the Fe ion beams prior to the shutdown. These goals have been achieved. A major effort was placed on collection, re-screening, and archiving of 3 different series of mutants for the various particle beam exposures: tk-ng mutants, tk-sg mutants, and hprt-deficient mutants. Where possible, groups of mutants were isolated for several particle fluences. Comparative analysis of mutation spectra has occured with characterization of the mutation spectrum for hprt-deficient mutants obtained after exposure of TK6 cells to Fe ions (600 MeV/amu) and a series of spontaneous mutants.

  14. Photoion mass spectroscopy and valence photoionization of hypoxanthine, xanthine and caffeine

    NASA Astrophysics Data System (ADS)

    Feyer, Vitaliy; Plekan, Oksana; Richter, Robert; Coreno, Marcello; Prince, Kevin C.

    2009-03-01

    Photoionization mass spectra of hypoxanthine, xanthine and caffeine were measured using the photoelectron-photoion coincidence technique and noble gas resonance radiation at energies from 8.4 to 21.2 eV for ionization. The fragmentation patterns for these compounds show that hydrogen cyanide is the main neutral loss species at higher photon energies, while photoionization below 16.67 eV led predominantly to the parent ion. The valence photoelectron spectra of this family of molecules were measured over an extended energy range, including the inner C, N and O 2s valence orbitals. The observed ion fragments were related to ionization of the valence orbitals.

  15. Comparison between yeast orotate - and hypoxanthine/guanine-phosphoribosyltransferase activities: NMR studies of the conformations of free and bound 5'-phosphoribosyl-. cap alpha. -1-pyrophosphate. Kinetic inhibition studies with Cr(III) pyrophosphate

    SciTech Connect

    Syed, D.B.

    1986-01-01

    This thesis describes the elucidation of Mn(II)-PRibPP conformations free in solution as well as bound to OPRTase and HGPRTase from yeast using /sup 1/H and /sup 31/P magnetic relaxation rate measurements. The eight PRibPP metal-to-nucleus distances determined were used to resolve the conformation of the binary Mn(II)-PRibPP, ternary OPRTase-Mn(II)-PRibPP and HGPRTase-Mn(II)-PRibPP complexes. In the case of the binary, Mn(II)-PRibPP complex, all the phosphates interact with the metal ion. The ..cap alpha..- and ..beta..-phosphates were observed to be directly coordinated, in a bidentate fashion, while 5'-PO/sub 4/ might be coordinated via axial oxygen. In this conformation the ..beta..-position of the C-1 carbon of ribose is essentially unavailable for on-line substitutions. The ribose ring of HGPRTase-bound PRibPP was also observed to position itself further away from the metal ion by a distance of 0.7 A. The new PRibPP conformation thus created would seem to allow for on-line displacement at the HGPRTase active site. Also described in this dissertation are the inhibition studies carried out on these enzyme activities with Cr(III)PP/sub i/ and Na(I)PP/sub i/ in the presence of 1-2mM Mg(II) ion. Based upon the elucidated conformations of PRibPP when bound to these enzymes. Upon inhibition studies with Cr(III)PP/sub i/ and Na(I)PP/sub i/ in presence of Mg(II) and upon previous kinetic and metal activation studies, the authors propose that one difference between the HGPRTase and OPRTase catalyzed reactions is how these enzymes make use of several metal-ions at their active sites to perform aspects of the catalysis.

  16. Dynamic architecture of the purinosome involved in human de novo purine biosynthesis.

    PubMed

    Kyoung, Minjoung; Russell, Sarah J; Kohnhorst, Casey L; Esemoto, Nopondo N; An, Songon

    2015-01-27

    Enzymes in human de novo purine biosynthesis have been demonstrated to form a reversible, transient multienzyme complex, the purinosome, upon purine starvation. However, characterization of purinosomes has been limited to HeLa cells and has heavily relied on qualitative examination of their subcellular localization and reversibility under wide-field fluorescence microscopy. Quantitative approaches, which are particularly compatible with human disease-relevant cell lines, are necessary to explicitly understand the purinosome in live cells. In this work, human breast carcinoma Hs578T cells have been utilized to demonstrate the preferential utilization of the purinosome under purine-depleted conditions. In addition, we have employed a confocal microscopy-based biophysical technique, fluorescence recovery after photobleaching, to characterize kinetic properties of the purinosome in live Hs578T cells. Quantitative characterization of the diffusion coefficients of all de novo purine biosynthetic enzymes reveals the significant reduction of their mobile kinetics upon purinosome formation, the dynamic partitioning of each enzyme into the purinosome, and the existence of three intermediate species in purinosome assembly under purine starvation. We also demonstrate that the diffusion coefficient of the purine salvage enzyme, hypoxanthine phosphoribosyltransferase 1, is not sensitive to purine starvation, indicating exclusion of the salvage pathway from the purinosome. Furthermore, our biophysical characterization of nonmetabolic enzymes clarifies that purinosomes are spatiotemporally different cellular bodies from stress granules and cytoplasmic protein aggregates in both Hs578T and HeLa cells. Collectively, quantitative analyses of the purinosome in Hs578T cells led us to provide novel insights for the dynamic architecture of the purinosome assembly. PMID:25540829

  17. Somatic cell gene mutations in humans: biomarkers for genotoxicity.

    PubMed Central

    Albertini, R J; Nicklas, J A; O'Neill, J P

    1993-01-01

    Somatic cell gene mutations arising in vivo in humans provide biomarkers for genotoxicity. Four assays, each measuring changes in a different "recorder" gene, are available for detecting mutations of the hemoglobin (Hb) and glycophorin A (gpa) genes in red blood cells and the hypoxanthine-guanine phosphoribosyltransferase (hprt) and HLA genes in T-lymphocytes. Mean adult background mutant frequencies have been established; i.e., approximately 4 x 10(-8) (Hb), 5-10 x 10(-6) (hprt), 10-20 x 10(-6) (gpa) and 30 x 10(-6) (HLA). All the assays have now been used in studies of individuals exposed to physical and/or chemical genotoxic agents, and all have shown elevated values following exposures; examples are presented. In addition to quantitation, the lymphocyte assays allow molecular analyses of in vivo mutations, the definition of background and induced mutational spectra, and the search for unique changes for characterizing specific mutagens. The HPRT system currently has the largest database in this regard. Approximately 15% of adult background hprt mutations are due to gross structural alterations (primarily deletions) having random breakpoints; 85% result from "point" changes detected only by sequencing. In contrast, a specific intragenic deletion due to DNA cleavage at specific sites characterizes fetal hprt mutations, implicating a developmental mistake in their genesis. (This kind of developmental mistake in other genes is frequently observed in lymphoid malignancies.) Mutational spectra are just beginning to be defined for induced hprt mutations, e.g., ionizing radiation produces large deletions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8143616

  18. Validation of adequate endogenous reference genes for the normalisation of qPCR gene expression data in human post mortem tissue

    Microsoft Academic Search

    Antje Koppelkamm; Benedikt Vennemann; Tony Fracasso; Sabine Lutz-Bonengel; Ulrike Schmidt; Marielle Heinrich

    2010-01-01

    Gene expression analyses based on messenger RNA (mRNA) profiling require accurate data normalisation. When using endogenous\\u000a reference genes, these have to be validated carefully. Therefore, we examined the transcript stability of 10 potential reference\\u000a genes using quantitative real-time polymerase chain reaction: beta actin, 18S rRNA, glyceraldehyde-3-phosphate dehydrogenase,\\u000a TATA box-binding protein, hypoxanthine phosphoribosyl-transferase I, beta-2-microglobulin, hydroxymethylbilane synthase, succinate\\u000a dehydrogenase complex, subunit

  19. Evaluating reference genes to normalize gene expression in human epileptogenic brain tissues.

    PubMed

    Wierschke, Stephan; Gigout, Sylvain; Horn, Peter; Lehmann, Thomas-Nicolas; Dehnicke, Christoph; Bräuer, Anja U; Deisz, Rudolf A

    2010-12-17

    Several reference genes have been used to quantify gene expression in human epilepsy surgery tissue. However, their reliability has not been validated in detail, although this is crucial in interpreting epilepsy-related changes of gene expression. We evaluated 12 potential reference genes in neocortical tissues resected from patients with temporal lobe epilepsy (TLE) with either few or many seizures (n=6 each) and post mortem controls (n=6) using geNorm and NormFinder algorithms. For all candidate reference genes threshold cycle (C(T)) values were measured. geNorm analysis revealed that the expression of e.g. glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and hypoxanthine phosphoribosyl-transferase (HPRT) is unstable, whereas synaptophysin (SYP) and neuron-specific enolase (NSE)/mitochondrial 39S ribosomal protein L28 (MRPL) are most stably expressed. The geometric mean of SYP, NSE and MRPL levels is recommended as normalization factor (NF). NormFinder analysis, in contrast, indicated HPRT as the most stable single gene and recommended the geometric mean of TATA-box binding protein (TBP) and NSE levels as NF. Different values of upregulation of glial fibrillary protein (GFAP) expression were found in TLE tissue compared to control tissue depending on the NF used: 4.5-fold (geNorm-NF), 4.7-fold (NormFinder-NF), 4.2-fold (vs. GAPDH) and 7.8-fold (vs. HPRT). The expression of GABA(A) receptor subunit ?5 (GAR?5) was unaltered in the TLE groups compared to controls (geNorm-NF, NormFinder-NF, vs. GAPDH). However, normalization to HPRT suggests an apparent increase of GAR?5 expression. In conclusion, the geNorm-NF (SYP/NSE/MRPL) and the NormFinder-NF (TBP/NSE) are equally suitable for normalization of gene expression in the human epileptogenic neocortex. In contrast, normalization to single and probably less stably expressed genes may not deliver accurate results. PMID:21081112

  20. IPO8 and FBXL10: new reference genes for gene expression studies in human adipose tissue.

    PubMed

    Hurtado del Pozo, Carmen; Calvo, Rosa M; Vesperinas-García, Gregorio; Gómez-Ambrosi, Javier; Frühbeck, Gema; Corripio-Sánchez, Ramón; Rubio, Miguel A; Obregon, Maria-Jesus

    2010-05-01

    Housekeeping genes frequently used in gene expression studies are highly regulated in human adipose tissue. To ensure a correct interpretation of results, it is critical to select appropriate reference genes. Subcutaneous (SC) and omental (OM) adipose tissue expression was analyzed from lean and obese subjects using whole genome complementary DNA (cDNA) microarrays to identify stably expressed genes and commercial TaqMan low density arrays (LDAs), with 16 common control genes. The best candidate gene from microarrays analysis was F-box and leucine-rich repeat protein-10 (FBXL10) (fold-change 10(-3) P < 0.01), an ubiquitous nucleolar protein evolutionarily conserved. Hypoxanthine phosphoribosyltransferase 1 (HPRT1) and importin 8 (IPO8), were the best reference genes among the 16 genes in the LDAs with coefficient of variation (CV) of 4.51 and 4.55%, respectively. However, when the LDAs data were further analyzed by the geNorm and NormFinder softwares, IPO8, a nuclear protein mediating import of proteins, was the first and the third better reference gene, respectively. IPO8 and FBXL10 were further validated by real-time PCR in additional OM and SC fat samples and primary cultured preadipocytes. According to their CV, IPO8 resulted more suitable than FBXL10 in both adipose tissue depots and SC preadipocytes, whereas FBXL10 performed better than IPO8 in OM cultured preadipocytes. Both genes expression levels did not change throughout adipogenesis. Thus, we provide clear evidence that IPO8 and FBXL10 are good candidates to use as reference genes in gene expression studies in human OM and SC adipose tissues as well as differentiated primary preadipocytes. PMID:19876011

  1. UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells†

    PubMed Central

    Durant, Stephen T.; Paffett, Kimberly S.; Shrivastav, Meena; Timmins, Graham S.; Morgan, William F.; Nickoloff, Jac A.

    2006-01-01

    Ionizing radiation induces delayed genomic instability in human cells, including chromosomal abnormalities and hyperrecombination. Here, we investigate delayed genome instability of cells exposed to UV radiation. We examined homologous recombination-mediated reactivation of a green fluorescent protein (GFP) gene in p53-proficient human cells. We observed an ?5-fold enhancement of delayed hyperrecombination (DHR) among cells surviving a low dose of UV-C (5 J/m2), revealed as mixed GFP+/? colonies. UV-B did not induce DHR at an equitoxic (75 J/m2) dose or a higher dose (150 J/m2). UV is known to induce delayed hypermutation associated with increased oxidative stress. We found that hypoxanthine phosphoribosyltransferase (HPRT) mutation frequencies were ?5-fold higher in strains derived from GFP+/? (DHR) colonies than in strains in which recombination was directly induced by UV (GFP+ colonies). To determine whether hypermutation was directly caused by hyperrecombination, we analyzed hprt mutation spectra. Large-scale alterations reflecting large deletions and insertions were observed in 25% of GFP+ strains, and most mutants had a single change in HPRT. In striking contrast, all mutations arising in the hypermutable GFP+/? strains were small (1- to 2-base) changes, including substitutions, deletions, and insertions (reminiscent of mutagenesis from oxidative damage), and the majority were compound, with an average of four hprt mutations per mutant. The absence of large hprt deletions in DHR strains indicates that DHR does not cause hypermutation. We propose that UV-induced DHR and hypermutation result from a common source, namely, increased oxidative stress. These two forms of delayed genome instability may collaborate in skin cancer initiation and progression. PMID:16880516

  2. Determination of Xanthine in the Presence of Hypoxanthine by Adsorptive Stripping Voltammetry at the Mercury Film Electrode

    PubMed Central

    Farias, Percio Augusto Mardini; Castro, Arnaldo Aguiar

    2014-01-01

    A stripping method for the determination of xanthine in the presence of hypoxanthine at the submicromolar concentration levels is described. The method is based on controlled adsorptive accumulation at the thin-film mercury electrode followed by a fast linear scan voltammetric measurement of the surface species. Optimum experimental conditions were found to be the use of 1.0 × 10?3 mol L?1 NaOH solution as supporting electrolyte, an accumulation potential of 0.00 V for xanthine and ?0.50 V for hypoxanthine–copper, and a linear scan rate of 200 mV second?1. The response of xanthine is linear over the concentration ranges of 20–140 ppb. For an accumulation time of 30 minutes, the detection limit was found to be 36 ppt (2.3 × 10?10 mol L?1). Adequate conditions for measuring the xanthine in the presence of hypoxanthine, copper and other metals, uric acid, and other nitrogenated bases were also investigated. The utility of the method is demonstrated by the presence of xanthine associated with hypoxanthine, uric acid, nitrogenated bases, ATP, and ssDNA. PMID:24940040

  3. Electrochemical sensor for simultaneous determination of uric acid, xanthine and hypoxanthine based on poly (bromocresol purple) modified glassy carbon electrode

    Microsoft Academic Search

    Yan Wang; Li-li Tong

    2010-01-01

    A novel electrochemical sensor based on electroactive-polymerized film of bromocresol purple (BCP) modified on glassy carbon electrode for simultaneous determination of uric acid (UA), xanthine (XA) and hypoxanthine (HX) was presented. The preparation and basic electrochemical performance of poly (BCP) film modified glassy carbon electrode were investigated firstly in details. The electrochemical behaviors of UA, XA and HX at the

  4. Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

    PubMed Central

    K?ikavová, Radka; Hošek, Jan; Van?o, Ján; Hutyra, Jakub; Dvo?ák, Zden?k; Trávní?ek, Zden?k

    2014-01-01

    A series of gold(I) complexes involving triphenylphosphine (PPh3) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HLn) of the general composition [Au(Ln)(PPh3)] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC50 ? 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-? (TNF-?) and interleukin-1? (IL-1?), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study. PMID:25226034

  5. In vivo mutations in human blood cells: Biomarkers for molecular epidemiology

    SciTech Connect

    Albertini, R.J.; Branda, R.F.; O'Neill, J.P. (Univ. of Vermont, Burlington (United States)); Nicklas, J.A.; Fuscoe, J.C. (Environmental Health Research and Testing, Inc., Research Triangle Park, NC (United States)); Skopek, T.R. (Univ. of North Carolina, Chapel Hill (United States))

    1993-03-01

    Mutations arising in vivo in recorder genes of human blood cells provide biomarkers for molecular epidemiology by serving as surrogates for cancer-causing genetic changes. Current markers include mutations of the glycophorin-A (GPA) or hemoglobin (Hb) genes, measured in red blood cells, or mutations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) or HLA genes, measured in T-lymphocytes. Mean mutant frequencies (variant frequencies) for normal young adults are approximately: Hb (4 [times] 10[sup [minus]8]) < hprt (5 [times] 10[sup [minus]6]) = GPA (10 [times] 10[sup [minus]6]) < HLA (30 [times] 10[sup [minus]6]). Mutagen-exposed individuals show decided elevations. Molecular mutational spectra are also being defined. For the hprt marker system, about 15% of background mutations are gross structural alterations of the hprt gene (e.g., deletions); the remainder are point mutations (e.g., base substitutions or frameshifts). Ionizing radiations result in dose-related increases in total gene deletions. Large deletions may encompass several megabases as shown by co-deletions of linked markers. Possible hprt spectra for defining radiation and chemical exposures are being sought. In addition to their responsiveness to environmental mutagens/carcinogens, three additional findings suggest that the in vivo recorder mutations are relevant in vivo surrogates for cancer mutations. First, a large fraction of GPA and HLA mutations show exchanges due to homologous recombination, an important mutational event in cancer. Second, hprt mutations arise preferentially in dividing T-cells, which can accumulate additional mutations in the same clone, reminiscent of the multiple hits required in the evolution of malignancy. Finally, fetal hprt mutations frequently have characteristic deletions of hprt exons 2 and 3, which appear to be mediated by the VDJ recombinase that rearranges the T-cell receptor genes during thymic ontogeny. 60 refs., 3 tabs.

  6. Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients.

    PubMed

    Kamatani, N; Hakoda, M; Otsuka, S; Yoshikawa, H; Kashiwazaki, S

    1992-07-01

    We analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency in Japanese patients. Among 141 defective APRT alleles from 72 different families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and duplication of a 4-bp sequence in exon 3, respectively. The disease-causing mutations of only four (3%) of all the alleles among Japanese remain to be elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient patients by identifying only three disease-causing mutations. All of the different alleles with the same mutation had the same haplotype, except for APRT*J alleles, thereby suggesting that alleles with the same mutation in different families were derived from the same ancestral gene. Evidence for a crossover or gene conversion event within the APRT gene was observed in an APRT*J mutant allele. Distribution of mutant alleles encoding APRT deficiency among the Japanese was similar to that seen in cystic fibrosis genes among Caucasians and Tay-Sachs genes among the Ashkenazi Jews. PMID:1353080

  7. Substrate Orientation and Catalytic Specificity in the Action of Xanthine Oxidase: The Sequential Hydroxylation of Hypoxanthine to Uric Acid

    SciTech Connect

    Cao, Hongnan; Pauff, James M.; Hille, Russ (UCR)

    2010-11-29

    Xanthine oxidase is a molybdenum-containing enzyme catalyzing the hydroxylation of a sp{sup 2}-hybridized carbon in a broad range of aromatic heterocycles and aldehydes. Crystal structures of the bovine enzyme in complex with the physiological substrate hypoxanthine at 1.8 {angstrom} resolution and the chemotherapeutic agent 6-mercaptopurine at 2.6 {angstrom} resolution have been determined, showing in each case two alternate orientations of substrate in the two active sites of the crystallographic asymmetric unit. One orientation is such that it is expected to yield hydroxylation at C-2 of substrate, yielding xanthine. The other suggests hydroxylation at C-8 to give 6,8-dihydroxypurine, a putative product not previously thought to be generated by the enzyme. Kinetic experiments demonstrate that >98% of hypoxanthine is hydroxylated at C-2 rather than C-8, indicating that the second crystallographically observed orientation is significantly less catalytically effective than the former. Theoretical calculations suggest that enzyme selectivity for the C-2 over C-8 of hypoxanthine is largely due to differences in the intrinsic reactivity of the two sites. For the orientation of hypoxanthine with C-2 proximal to the molybdenum center, the disposition of substrate in the active site is such that Arg880 and Glu802, previous shown to be catalytically important for the conversion of xanthine to uric acid, play similar roles in hydroxylation at C-2 as at C-8. Contrary to the literature, we find that 6,8-dihydroxypurine is effectively converted to uric acid by xanthine oxidase.

  8. Clonal Analysis Using Recombinant DNA Probes from the X-Chromosome1

    Microsoft Academic Search

    Bert Vogelstein; Eric R. Fearon; Ann C. Preisinger; Huntington F. VVillard; Alan M. Michelson; Arthur D. Riggs; Stuart H. Orkin

    1987-01-01

    It has been demonstrated that restriction fragment length polymor phisms of X-chromosomegenes can be used in conjunction with methyl- ation patterns to determine the clonal composition of human tumors. In this report, we show that several \\\\-chromosome probes can be used for such analyses. In particular, probes derived from the hypoxanthine phosphoribosyltransferase gene and the phosphoglycerate kinase gene could be

  9. Analysis of kinetics of dihydroethidium fluorescence with superoxide using xanthine oxidase and hypoxanthine assay.

    PubMed

    Chen, Juan; Rogers, Steven C; Kavdia, Mahendra

    2013-02-01

    Superoxide (O(2) (-)) is an important reactive oxygen species (ROS), and has an essential role in physiology and pathophysiology. An accurate detection of O(2) (-) is needed to better understand numerous vascular pathologies. In this study, we performed a mechanistic study by using the xanthine oxidase (XOD)/hypoxanthine (HX) assay for O(2) (-) generation and a O(2) (-) sensitive fluorescent dye dihydroethidium (DHE) for O(2) (-) measurement. To quantify O(2) (-) and DHE interactions, we measured fluorescence using a microplate reader. We conducted a detailed reaction kinetic analysis for DHE-O(2) (-) interaction to understand the effect of O(2) (-) self-dismutation and to quantify DHE-O(2) (-) reaction rate. Fluorescence of DHE and 2-hydroethidium (EOH), a product of DHE and O(2) (-) interaction, were dependent on reaction conditions. Kinetic analysis resulted in a reaction rate constant of 2.169 ± 0.059 × 10(3) M(-1) s(-1) for DHE-O(2) (-) reaction that is ~100× slower than the reported value of 2.6 ± 0.6 × 10(5) M(-1) s(-1). In addition, the O(2) (-) self-dismutation has significant effect on DHE-O(2) (-) interaction. A slower reaction rate of DHE with O(2) (-) is more reasonable for O(2) (-) measurements. In this manner, the DHE is not competing with superoxide dismutase and NO for O(2) (-). Results suggest that an accurate measurement of O(2) (-) production rate may be difficult due to competitive interference for many factors; however O(2) (-) concentration may be quantified. PMID:22965641

  10. Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG)

    E-print Network

    Lee, Chun-Yue I.

    The human 3-methyladenine DNA glycosylase (AAG) recognizes and excises a broad range of purines damaged by alkylation and oxidative damage, including 3-methyladenine, 7-methylguanine, hypoxanthine (Hx), and 1,N[superscript ...

  11. Cytotoxicity of the hypoxanthine-xanthine oxidase system on V79 cells: comparison of the effects of SOD and CuDIPS.

    PubMed

    Tachon, P

    1989-01-01

    The hypoxanthine - xanthine oxidase system generates an extracellular flux of superoxide anion radical (O2.-) and hydrogen peroxide (H2O2). Catalase but not superoxide dismutase (SOD) protects V79 cells exposed to the hypoxanthine - xanthine oxidase system, showing that H2O2 is the major reactive oxygen species involved in the cytotoxicity of such a system. In contrast to SOD, the lipophilic SOD like compound CuII (diisopropylsalicylate)2 (CuDIPS) exhibits some protection at non cytotoxic concentration. It is also found that methanol partially protects cells exposed to the hypoxanthine-xanthine oxidase system. It appears that in our experimental conditions (temperature, ionic strength and pH) the protective effect afforded by methanol and CuDIPS is due to the inhibition of the xanthine oxidase activity. PMID:2583553

  12. Localization of the gene that codes for adenine phosphoribosyltransferase on the genetic map of chromosome 8 of mouse

    SciTech Connect

    Nesterova, T.B.; Borodin, P.M.; Zakiyan, S.M.

    1988-11-01

    Polymorphism of electrophoretic mobility of adenine phosphoribosyltransferase (APRT) was found in Mus musculus bactrianus, a population of domestic mouse. The presence of intraspecies polymorphism allows localization of the gene that codes for this enzyme on the genetic map of the 8th chromosome. Two markers were utilized to map the Aprt gene: the plasmin esterase-1, which is coded by the gene Es-1 located at a distance of 26 morganids from the centromere; and the Robertsonian translocation Rb(8.17)1 Iem, which marks the centromere. Results of the linkage analysis showed the gene Aprt to be located on the genetic map of the 8th chromosome at a distance of 51 morganids from the centromere and 25 morganids distil of the gene Es-1. Also discussed in this work was the influence of emotional stress on the recombination process in the 8th chromosome.

  13. Crystallization and preliminary X-ray crystallographic analysis of quinolinate phosphoribosyltransferase from porcine kidney in complex with nicotinate mononucleotide

    PubMed Central

    Youn, Hyung-Seop; Kim, Mun-Kyoung; Kang, Gil Bu; Kim, Tae Gyun; An, Jun Yop; Lee, Jung-Gyu; Park, Kyoung Ryoung; Lee, Youngjin; Fukuoka, Shin-Ichi; Eom, Soo Hyun

    2012-01-01

    Quinolinate phosphoribosyltransferase (QAPRTase) is a key enzyme in NAD biosynthesis; it catalyzes the formation of nicotinate mononucleotide (NAMN) from quinolinate and 5-phosphoribosyl-1-pyrophosphate. In order to elucidate the mechanism of NAMN biosynthesis, crystals of Sus scrofa QAPRTase (Ss-­QAPRTase) purified from porcine kidney in complex with NAMN were obtained and diffraction data were collected and processed to 2.1?Å resolution. The Ss-QAPRTase–NAMN cocrystals belonged to space group P321, with unit-cell parameters a = 119.1, b = 119.1, c = 93.7?Å, ? = 120.0°. The Matthews coefficient and the solvent content were estimated as 3.10?Å3 Da–1 and 60.3%, respectively, assuming the presence of two molecules in the asymmetric unit. PMID:23192029

  14. Perspectives on fast-neutron mutagenesis of human lymphoblastoid cells.

    PubMed

    Kronenberg, A

    1991-10-01

    The effects of low-fluence exposures to (Pu, Be) neutrons (En = 4.2 MeV) have been studied in a sensitive human B-lymphoblastoid cell line, TK6. Mutations were scored for two genetic loci, hypoxanthine phosphoribosyltransferase (hgprt) and thymidine kinase (tk), as a function of dose and dose rate. For exposures limited to less than one cell cycle, the mutation frequency for the hgprt locus was 1.92 X 10(-7)/cGy. When exposures were protracted over multiple cell generations, mutation yields were increased to 6.07 X 10(-7)/cGy. Similar yields were obtained for the induction of tk-deficient mutants with a normal cell generation time (tk-ng) when exposures were carried out at very low dose rates over multiple cell generations. In the series of data presented here, the results obtained for short-duration neutron exposures are compared with data obtained for monoenergetic heavy charged particles of defined linear energy transfer (LET) produced at the BEVALAC accelerator at Lawrence Berkeley Laboratory. TK6 cells have been exposed to beams ranging in atomic number from 20Ne to 40Ar over an energy range from 330 to 670 MeV/amu. Mutation induction was evaluated for both loci for a subset of these beams. The results obtained with 20Ne ions of 425 MeV/amu (LET = 32 keV/microns) and 28Si ions of 670 MeV/amu (LET = 50 keV/microns) closely resemble the mutation yields obtained for brief exposures to (Pu, Be) neutrons. The nature of alterations in DNA structure induced within the tk locus of tk-ng mutants is reviewed for a series of neutron-induced mutants and a series of mutants induced by exposure to 40Ar ions (470 MeV/amu, LET = 95 keV/microns). The mutational spectra for these two types of mutants were similar and were dominated by allele loss mutations. Multilocus deletions inclusive of the c-erbA1 locus were common among tk-deficient mutants induced by these densely ionizing radiations. For the mutants induced by 40Ar ions, it is likely that the mutations were produced by the traversal of the chromosome by a single particle. PMID:1924755

  15. Passage to Nonselective Media Transiently Alters Growth of Mycophenolic Acid-Resistant Mammalian Cells Expressing the Escherichia coliXanthine–Guanine Phosphoribosyltransferase Gene: Implications for Sequential Selection Strategies

    Microsoft Academic Search

    Reed E. Drews; Mitchell T. Kolker; David S. Sachar; Colin P. Moran; Lowell E. Schnipper

    1996-01-01

    TheEscherichia colixanthine–guanine phosphoribosyltransferase gene (Ecogpt) rescues mammalian cells from inhibition of purine nucleotide biosynthesis by mycophenolic acid (MPA). We usedEcogptand other selectable markers to obtain subclones of NIH 3T3 derivatives (EN\\/NIH) stably expressing transfected genes of interest. In their respective selective mediums, growth of MPA-resistant (MPAR) isolates was indistinguishable from that of aminoglycoside-resistant counterparts expressing selectable marker genes conferring resistance

  16. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells.

    PubMed

    Wang, Jing J; Sanderson, Barbara J S; Wang, He

    2007-04-01

    Titanium dioxide is frequently used in the production of paints, paper, plastics, welding rod-coating material, and cosmetics, because of its low toxicity. However, recent studies have shown that nano-sized or ultrafine TiO(2) (UF-TiO(2)) (<100 nm in diameter) can generate pulmonary fibrosis and lung tumor in rats. Cytotoxicity induced by UF-TiO(2) in rat lung alveolar macrophages was also observed. This generates great concern about the possible adverse effects of UF-TiO(2) for humans. The cytotoxicity and genotoxicity of UF-TiO(2) were investigated using the methyl tetrazolium cytotoxicity (MTT) assay, the population growth assay, the apoptosis assay by flow cytometry, the cytokinesis block micronucleus (CBMN) assay, the comet assay, and the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation assay. WIL2-NS cells were incubated for 6, 24 and 48 h with 0, 26, 65 and 130 microg/ml UF-TiO(2). Significant decreases in viability were seen in the MTT assay at higher doses; for example, 61, 7 and 2% relative viability at 130 microg/ml for 6, 24 and 48-h exposure (P<0.01). A dose-dependent relationship was observed, while a time-dependent relationship was seen only at the highest dose (130 microg/ml) after exposure for 24 and 48 h. Treatment with 130 microg/ml UF-TiO(2) induced approximately 2.5-fold increases in the frequency of micronucleated binucleated cells (P<0.01). In addition, a significant reduction in the cytokinesis block proliferation index was observed by the CBMN assay (P<0.05). In the comet assay, treatment with 65 microg/ml UF-TiO(2) induced approximately 5-fold increases in olive tail moment (P<0.05). In the HPRT mutation assay, treatment with 130 microg/ml UF-TiO(2) induced approximately 2.5-fold increases in the mutation frequency (P<0.05). The results of this study indicate that UF-TiO(2) can cause genotoxicity and cytotoxicity in cultured human cells. PMID:17223607

  17. Bisphosphonates activate the 5-fluorouracil/uracil phosphoribosyltransferase activity present in Saccharomyces cerevisiae cell extracts: implications for tumor treatments.

    PubMed

    Pérez-Zúñiga, Francisco J; Günther Sillero, María A; Sillero, Antonio

    2008-10-01

    Most of the effects described for bisphosphonates (pC(R1)(R2)p) are related, directly or indirectly with a pyrophosphate moiety. Bisphosphonates are (i) analogs of pyrophosphate in the synthesis of ATP derivatives (AppC(R1)(R2)p) catalyzed by ligases and (ii) inhibitors of enzymes of the mevalonate pathway with substrates containing a terminal pyrophosphate. Searching for the role of bisphosphonates on other reactions involving pyrophosphate, we explored their effect on a phosphoribosyltransferase activity, present in Saccharomyces cerevisiae cell extracts, using 5-fluorouracil or uracil as substrates. Unexpectedly, bisphosphonates increased the initial rate of synthesis of 5-FUMP (from 5-fluorouracil and phosphoribosylpyrophosphate): etidronate (2.8+/-0.3 times); pamidronate (2.6+/-0.4 times); alendronate (2.5+/-0.6 times) and clodronate (2.0+/-0.1 times). Similar values for the synthesis of UMP (from uracil and phosphoribosylpyrophosphate) were obtained in the presence of bisphosphonates. The values of the activation constants determined for alendronate and clodronate for the synthesis of UMP were 0.05+/-0.02 mM and 0.32+/-0.22 mM, respectively. These results raise the possibility that bisphosphonates enhance the effect of 5-fluorouracil (or other uracil prodrugs) in the treatment of bone tumors or bone tumor metastases. PMID:18706399

  18. The synthetic substance hypoxanthine 3- N-oxide elicits alarm reactions in zebrafish ( Danio rerio)

    Microsoft Academic Search

    Kevin V. Parra; James C. Adrian Jr.; Robert Gerlai

    2009-01-01

    Zebrafish, one of the preferred study species of geneticists, is gaining increasing popularity in behavioral neuroscience. This small and prolific species may be an excellent tool with which the biological mechanisms of vertebrate brain function and behavior are investigated. Zebrafish has been proposed as a model organism in the analysis of fear responses and human anxiety disorders. Species-specific cues signaling

  19. Biochemical Characterization of Quinolinic Acid Phosphoribosyltransferase from Mycobacterium tuberculosis H37Rv and Inhibition of Its Activity by Pyrazinamide

    PubMed Central

    Kim, Hyun; Shibayama, Keigo; Rimbara, Emiko; Mori, Shigetarou

    2014-01-01

    Quinolinic acid phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) is a key enzyme in the de novo pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis and a target for the development of new anti-tuberculosis drugs. QAPRTase catalyzes the synthesis of nicotinic acid mononucleotide from quinolinic acid (QA) and 5-phosphoribosyl-1-pyrophosphate (PRPP) through a phosphoribosyl transfer reaction followed by decarboxylation. The crystal structure of QAPRTase from Mycobacterium tuberculosis H37Rv (MtQAPRTase) has been determined; however, a detailed functional analysis of MtQAPRTase has not been published. Here, we analyzed the enzymatic activities of MtQAPRTase and determined the effect on catalysis of the anti-tuberculosis drug pyrazinamide (PZA). The optimum temperature and pH for MtQAPRTase activity were 60°C and pH 9.2. MtQAPRTase required bivalent metal ions and its activity was highest in the presence of Mg2+. Kinetic analyses revealed that the Km values for QA and PRPP were 0.08 and 0.39 mM, respectively, and the kcat values for QA and PRPP were 0.12 and 0.14 [s-1], respectively. When the amino acid residues of MtQAPRTase, which may interact with QA, were substituted with alanine residues, catalytic activity was undetectable. Further, PZA, which is an anti-tuberculosis drug and a structural analog of QA, markedly inhibited the catalytic activity of MtQAPRTase. The structure of PZA may provide the basis for the design of new inhibitors of MtQAPRTase. These findings provide new insights into the catalytic properties of MtQAPRTase. PMID:24949952

  20. Interactions at the 2 and 5 positions of 5-phosphoribosyl pyrophosphate are essential in Salmonella typhimurium quinolinate phosphoribosyltransferase†

    PubMed Central

    Bello, Zainab; Stitt, Barbara; Grubmeyer, Charles

    2010-01-01

    Quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) catalyzes an unusual phosphoribosyl transfer that is linked to a decarboxylation reaction to form the NAD precursor nicotinate mononucleotide, carbon dioxide, and pyrophosphate from quinolinic acid (QA) and 5-phosphoribosyl 1-pyrophosphate (PRPP). Structural studies and sequence similarities with other PRTases have implicated Glu214, Asp235, Lys153 and Lys284 in contributing to catalysis through direct interaction with PRPP. The four residues were substituted by site-directed mutagenesis. A nadC deletant form of BL21DE3 was created to eliminate trace contamination by chromosomal QAPRTase. The mutant enzymes were readily purified and retained their dimeric aggregation state on gel filtration. Substitution of Lys153 with Ala resulted in an inactive enzyme, indicating its essential nature. Mutation of Glu214 to Ala or Asp caused at least a 4000-fold reduction in kcat, with 10-fold increases in Km and KD values for PRPP. However, mutation of Glu214 to Gln had only modest effects on ligand binding and catalysis. pH profiles indicated that the deprotonated form of a residue with pKa of 6.9 is essential for catalysis. The WT-like pH-profile of the E214Q mutant indicated that Glu214 is not that residue. Mutation of Asp235 to Ala did not affect ligand binding or catalysis. Mutation of Lys284 to Ala decreased kcat by 30-fold and increased Km and KD values for PRPP by 80-fold and at least 20-fold, respectively. The study suggests that Lys153 is necessary for catalysis and important for PRPP binding, Glu214 provides a hydrogen bond necessary for catalysis but does not act as a base or electrostatically to stabilize the transition state, Lys284 is involved in PRPP binding and Asp235 is not essential. PMID:20047307

  1. Non-invasive molecular and functional imaging of cytosine deaminase and uracil phosphoribosyltransferase fused with red fluorescence protein

    PubMed Central

    XING, LIGANG; DENG, XUELONG; KOTEDIA, KHUSHALI; ACKERSTAFF, ELLEN; PONOMAREV, VLADIMIR; LING, C. CLIFTON; KOUTCHER, JASON A.; LI, GLORIA C.

    2014-01-01

    Introduction Increased expression of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) may improve the antitumoral effect of 5-fluorouracil (5-FU) and 5-fluorocytosine (5-FC), and thereby enhance the potential of gene-directed enzyme prodrug therapy. For the applicability of gene-directed enzyme prodrug therapy in a clinical setting, it is essential to be able to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using magnetic resonance spectroscopy and optical imaging to measure non-invasively CD and UPRT expression and function. Materials and methods Expression vectors of CD or CD/UPRT fused to monomeric DsRed (mDsRed) were constructed and rat prostate carcinoma (R3327-AT) cell lines stably expressing either CD/mDsRed or CD/UPRT/mDsRed were generated. The expression of the fusion proteins was evaluated by flow cytometry, fluorescence microscopy, and Western blot analysis. The function of the fusion protein was confirmed in vitro by assessing 5-FC and 5-FU cytotoxicity. In vivo fluorine-19 magnetic resonance spectroscopy (19F MRS) was used to monitor the conversion of 5-FC to 5-FU in mice bearing the R3327-CD/mDsRed and R3327-CD/UPRT/mDsRed tumor xenografts. Results Sensitivity to 5-FC and 5-FU was higher in cells stably expressing the CD/UPRT/mDsRed fusion gene than in cells stably expressing CD/mDsRed alone or wild-type cells. Whole tumor 19F MRS measurements showed rapid conversion of 5-FC to 5-FU within 20 min after 5-FC was administered intravenously in both CD/mDsRed and CD/UPRT/mDsRed tumors with subsequent anabolism to cytotoxic fluoronucleotides (FNucs). CD/UPRT/mDsRed tumor was more efficient in these processes. Conclusion This study demonstrates the utility of these tumor models stably expressing CD or CD/UPRT to non-invasively evaluate the efficacy of the transgene expression/activity by monitoring drug metabolism in vivo using MRS, with potential applications in preclinical and clinical settings. PMID:18661431

  2. The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

    SciTech Connect

    Mesarosova, Monika; Valovicova, Zuzana; Srancikova, Annamaria [Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia); Krajcovicova, Zdenka [Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia); Alexander Dubcek University of Trencin, Studentska 2, 911 01 Trencin (Slovakia); Milcova, Alena [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20 Prague 4 (Czech Republic); Sokolova, Romana [J. Heyrovsky Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic, Dolejskova 3, 18223 Prague (Czech Republic); Schmuczerova, Jana; Topinka, Jan [Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20 Prague 4 (Czech Republic); Gabelova, Alena, E-mail: alena.gabelova@savba.sk [Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia)

    2011-09-15

    The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). A slight but significant level of gene mutations and DNA adducts detected in V79MZh3A4 cells treated with N-MeDBC, only at the highest concentration (30 {mu}M), revealed that this sarcomagenic carcinogen was also metabolized by hCYP3A4. Surprisingly, DBC increased the frequency of 6-thioguanine resistant (6-TG{sup r}) mutations only at the highest concentration (30 {mu}M), while DiMeDBC failed to increase the frequency of these mutations. The resistance to 6-thioguanine is caused by the mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene. The molecular analysis of the coding region of Hprt gene showed a deletion of the entire exon 8 in DiMeDBC-induced 6-TG{sup r} mutants, while no changes in the nucleotide sequences were identified in 6-TG{sup r} mutants produced by DBC and N-MeDBC. Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism. - Highlights: > DBC activation via CYP3A4 resulted in micronuclei, DNA adduct formation and mutations in V79MZh3A4 cells. > The CYP3A4-mediated DiMeDBC activation caused micronuclei followed by apoptosis in V79MZh3A4 cells. > The genotoxic effects produced by N-MeDBC in V79MZh3A4 cells were negligible. > The hCYP3A4 may play an important role in DBC and DiMeDBC metabolism. > The CYP3A4 might only have a marginal function in N-MeDBC metabolism.

  3. Bilirubin UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Promoter Polymorphisms and HPRT, Glycophorin A, and Micronuclei Mutant Frequencies in Human Blood

    SciTech Connect

    Grant, D; Hall, I J; Eastmond, D; Jones, I M; Bell, D A

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and genetic damage will be needed.

  4. Hypoxanthine uptake by skeletal muscle microvascular endothelial cells from equilibrative nucleoside transporter 1 (ENT1)-null mice: Effect of oxidative stress.

    PubMed

    Bone, D B J; Antic, M; Quinonez, D; Hammond, J R

    2015-03-01

    Adenosine is an endogenous regulator of vascular tone. This activity of adenosine is terminated by its uptake and metabolism by microvascular endothelial cells (MVEC). The predominant transporter involved is ENT1 (equilibrative nucleoside transporter subtype 1). MVEC also express the nucleobase transporter (ENBT1) which is involved in the cellular flux of adenosine metabolites such as hypoxanthine. Changes in either of these transport systems would impact the bioactivity of adenosine and its metabolism, including the formation of oxygen free radicals. MVEC isolated from skeletal muscle of ENT1(+/+) and ENT1(-/-) mice were subjected to oxidative stress induced by simulated ischemia/reperfusion or menadione. The functional activities of ENT1 and ENBT1 were assessed based on zero-trans influx kinetics of radiolabeled substrates. There was a reduction in the rate of ENBT1-mediated hypoxanthine uptake by ENT1(+/+) MVEC treated with menadione or after exposure to conditions that simulate ischemia/reperfusion. In both cases, the superoxide dismutase mimetic MnTMPyP attenuated the loss of ENBT1 activity, implicating superoxide radicals in the response. In contrast, MVEC isolated from ENT1(-/-) mice showed no reduction in ENBT1 activity upon treatment with menadione or simulated ischemia/reperfusion, but they did have a significantly higher level of catalase activity relative to ENT1(+/+) MVEC. These data suggest that ENBT1 activity is decreased in MVEC in response to the increased superoxide radical that is associated with ischemia/reperfusion injury. MVEC isolated from ENT1(-/-) mice do not show this reduction in ENBT1, possibly due to increased catalase activity. PMID:25448155

  5. Comparison of SYBR Green I-, PicoGreen-, and [3H]-hypoxanthine-based assays for in vitro antimalarial screening of plants from Nigerian ethnomedicine.

    PubMed

    Abiodun, Oyindamola O; Gbotosho, Grace O; Ajaiyeoba, Edith O; Happi, Christian T; Hofer, Sandra; Wittlin, Sergio; Sowunmi, Akin; Brun, Reto; Oduola, Ayoade M J

    2010-03-01

    The standard method for in vitro antimalarial drug screening is based on the isotopic assay which is expensive and utilizes radioactive materials with limited availability, safety, and disposal problems in developing countries. The use of non-radioactive DNA stains SYBR Green I (SG) and PICO green (PG) for antimalarial screening had been reported. However, the use of the two DNA stains for antimalarial screening of medicinal plants has not been compared. Thus, this study compared SG, PG with the [(3)H]-hypoxanthine (HP) incorporation assays for in vitro antimalarial screening of medicinal plants. The 50% inhibitory concentration (IC(50)) values obtained using the three methods for antimalarial activity of medicinal plants and standard antimalarial drugs were similar. Data generated from this study suggests that the non-radioactive micro-flourimetric assay is sufficiently sensitive to reproducibly identify plant extracts with antimalarial activity from those lacking activity. The HP-based assay exhibited the most robust signal-to-noise ratio of 100, compared with signal-to-noise ratios of 7 for SG and 8 for PG. The SG-based assay is less expensive than the PG- and HP-based assays. SG appears to be a cost-effective alternative for antimalarial drug screening and a viable technique that may facilitate antimalarial drug discovery process especially in developing countries. PMID:20165881

  6. ANALYSIS OF X-RAY INDUCED HPRT MUTATIONS IN CHO CELLS: INSERTION AND DELETIONS

    EPA Science Inventory

    Molecular alterations were examined in the hypoxanthine guanine phosphoribosyltransferase (hprt) gene of 41 independent X-ray-induced thioguanine-resistant (TGR) Chinese hamster ovary (CHO) cell clones. Rapid screening of the clones by multiplex polymerase chain reaction (PCR) fo...

  7. The Salmonella typhimurium nadC gene: sequence determination by use of Mud-P22 and purification of quinolinate phosphoribosyltransferase.

    PubMed Central

    Hughes, K T; Dessen, A; Gray, J P; Grubmeyer, C

    1993-01-01

    The Salmonella typhimurium nadC gene and its product, quinolinic acid phosphoribosyltransferase (QAPRTase), were characterized at the molecular and biochemical levels. Fusions of Mud-lac elements isolated in the nadC gene were converted to Mud-P22 insertions. Starting with six original Mud-lac fusions, the entire sequence of the nadC gene was readily obtained. The sequence shows a long open reading frame with two potential initiator methionines, one of which is preceded by the Shine-Dalgarno sequence GGAG-7-nucleotide-ATG. The protein predicted from this second open reading frame is 297 residues in length. The nadC gene was subcloned into a T7-based expression system, allowing for facile purification of the QAPRTase (EC 2.4.2.19) protein to homogeneity. Upon gel filtration, the protein gave an M(r) of 72,000, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a subunit M(r) of 35,000. Automated Edman degradation of several tryptic peptides confirmed the amino acid sequence predicted from the DNA sequence. Chromatography of the apparently homogeneous enzyme on reverse-phase high-performance liquid chromatography resolved two protein species. One of these species failed to give an amino-terminal sequence, while the other yielded the amino-terminal sequence predicted by the second open reading frame and lacked the initiator methionine. The mass of the mature protein, predicted from its DNA sequence, was 32,428 Da. Electrospray mass spectrometry gave masses of 32,501 and 32,581 Da for the two peptides. Steady-state kinetics on the purified QAPRTase indicated Km values of 32 microM for 5-phosphoribosyl-1-pyrophosphate and 20 microM for quinolinate. Vmax was 0.9 U/mg, similar to values reported for this enzyme by other sources. Images PMID:8419294

  8. 2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT.

    PubMed

    Deng, L; Yang, M; Fründ, S; Wessel, T; De Abreu, R A; Tischfield, J A; Sahota, A

    2001-03-01

    We have examined the mutational basis of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency (MIM 102600) in a patient of Polish origin who has been passing 2,8-dihydroxyadenine (DHA) stones since birth, but has considerable residual enzyme activity in lymphocyte extracts. The five exons and flanking regions of APRT were amplified by PCR and then sequenced. A single T insertion was identified at the intron 4 splice donor site (TGgtaa to TGgttaa:IVS4+2insT) in one allele from the proband, his mother, and brother. A G-to-T transversion in exon 5 (GTC-to-TTC:c.448G>T, V150F) was identified in the other allele, and this mutation was also present in one allele from the father and the paternal grandmother. Tru91 and AvaII digestions of PCR products spanning exons 4 and 5, respectively, confirmed the mutations. The mother was heterozygous for an intragenic TaqI site, but all other family members were homozygous for the presence of this site. IVS4+2insT, located on the allele containing the TaqI site, has been identified previously in several families from Europe, suggesting a founder effect, but the substitution in exon 5 is a novel mutation. IVS4+2insT is known to result in complete loss of enzyme activity, and our results suggest that V150F produces an enzyme that is nonfunctional in vivo but has considerable residual activity in vitro. PMID:11243733

  9. Human somatic mutation assays as biomarkers of carcinogenesis

    SciTech Connect

    Compton, P.J.E.; Smith, M.T. (Univ. of California, Berkeley (United States)); Hooper, K. (California Dept. of Health Services, Berkeley (United States))

    1991-08-01

    This paper describes four assays that detect somatic gene mutations in humans: the hypoxanthine-guanine phosphoribosyl transferase assay, the glycophorin A assay, the HLA-A assay, and the sickle cell hemoglobin assay. Somatic gene mutations can be considered a biomarker of carcinogenesis, and assays for somatic mutation may assist epidemiologists in studies that attempt to identify factors associated with increased risks of cancer. Practical aspects of the use of these assays are discussed.

  10. Quantitative assay for mutation in diploid human lymphoblasts using microtiter plates

    SciTech Connect

    Furth, E.A.; Thilly, W.G.; Penman, B.W.; Liber, H.L.; Rand, W.M.

    1981-01-01

    A microtiter plating technique which eliminates the need for soft agar and fibroblast feeder layers to determine the colony-forming ability of diploid human lymphoblast lines was described. The calculation of cloning efficiency is based on the Poisson distribution, and a statistical method for calculating confidence intervals is presented. This technique has been applied to the comcomitant examination of induced mutation at the putative loci for hypoxanthine guanine phosphoribosyl transferase, thymidine, kinase, and Na/sup +//K/sup +/ adenosine triphosphatase.

  11. The human ?-amyloid precursor protein: biomolecular and epigenetic aspects.

    PubMed

    Nguyen, Khue Vu

    2015-03-01

    Abstract Beta-amyloid precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. APP plays a central role in Alzheimer's disease (AD) pathogenesis: APP processing generates ?-amyloid (A?) peptides, which are deposited as amyloid plaques in the brains of AD individuals; point mutations and duplications of APP are causal for a subset of early-onset familial AD (FAD) (onset age <65 years old). However, these mutations in FAD represent a very small percentage of cases (?1%). Approximately 99% of AD cases are nonfamilial and late-onset, i.e., sporadic AD (SAD) (onset age >65 years old), and the pathophysiology of this disorder is not yet fully understood. APP is an extremely complex molecule that may be functionally important in its full-length configuration, as well as the source of numerous fragments with varying effects on neural function, yet the normal function of APP remains largely unknown. This article provides an overview of our current understanding of APP, including its structure, expression patterns, proteolytic processing and putative functions. Importantly, and for the first time, my recent data concerning its epigenetic regulation, especially in alternative APP pre-mRNA splicing and in the control of genomic rearrangements of the APP gene, are also reported. These findings may provide new directions for investigating the role of APP in neuropathology associated with a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt) found in patients with Lesch-Nyhan syndrome (LNS) and its attenuated variants (LNVs). Also, these findings may be of significance for research in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases such as autism, fragile X syndrome (FXS) and AD, with its diversity and complexity, SAD in particular. Accurate quantification of various APP-mRNA isoforms in brain tissues is needed, and antisense drugs are potential treatments. PMID:25719338

  12. Functional Identification of the Hypoxanthine/Guanine Transporters YjcD and YgfQ and the Adenine Transporters PurP and YicO of Escherichia coli K-12*

    PubMed Central

    Papakostas, Konstantinos; Botou, Maria; Frillingos, Stathis

    2013-01-01

    The evolutionarily broad family nucleobase-cation symporter-2 (NCS2) encompasses transporters that are conserved in binding site architecture but diverse in substrate selectivity. Putative purine transporters of this family fall into one of two homology clusters: COG2233, represented by well studied xanthine and/or uric acid permeases, and COG2252, consisting of transporters for adenine, guanine, and/or hypoxanthine that remain unknown with respect to structure-function relationships. We analyzed the COG2252 genes of Escherichia coli K-12 with homology modeling, functional overexpression, and mutagenesis and showed that they encode high affinity permeases for the uptake of adenine (PurP and YicO) or guanine and hypoxanthine (YjcD and YgfQ). The two pairs of paralogs differ clearly in their substrate and ligand preferences. Of 25 putative inhibitors tested, PurP and YicO recognize with low micromolar affinity N6-benzoyladenine, 2,6-diaminopurine, and purine, whereas YjcD and YgfQ recognize 1-methylguanine, 8-azaguanine, 6-thioguanine, and 6-mercaptopurine and do not recognize any of the PurP ligands. Furthermore, the permeases PurP and YjcD were subjected to site-directed mutagenesis at highly conserved sites of transmembrane segments 1, 3, 8, 9, and 10, which have been studied also in COG2233 homologs. Residues irreplaceable for uptake activity or crucial for substrate selectivity were found at positions occupied by similar role amino acids in the Escherichia coli xanthine- and uric acid-transporting homologs (XanQ and UacT, respectively) and predicted to be at or around the binding site. Our results support the contention that the distantly related transporters of COG2233 and COG2252 use topologically similar side chain determinants to dictate their function and the distinct purine selectivity profiles. PMID:24214977

  13. Selective removal of ATP degradation products from food matrices II: Rapid screening of hypoxanthine and inosine by molecularly imprinted matrix solid-phase dispersion for evaluation of fish freshness.

    PubMed

    Cela-Pérez, M C; Barbosa-Pereira, L; Vecino, X; Pérez-Ameneiro, M; Lasagabaster Latorre, Aurora; López-Vilariño, J M; González Rodríguez, M V; Moldes, A B; Cruz, J M

    2015-04-01

    A water compatible molecularly imprinted polymer (MIP), synthesized using theophylline (TPH) as dummy-template and acrylamide (AM) as functional monomer, has been employed as supporting material in matrix solid-phase dispersion combined with ultra performance liquid chromatography-photodiode array detection (MSPD-UPLC-PDA) for selective determination of adenosine triphosphate (ATP) derivatives in fish samples. ATP degradation products are used as freshness index for assessment of fish quality. The solid sample was directly blended with MIP in MSPD procedure resulting in sample disruption and subsequent adsorption of the compounds on the MIP. By using n-hexane and ammonium hydroxide aqueous solution at pH 9 as the washing and elution solvent, respectively, satisfactory recoveries and clean chromatograms have been obtained. Good linearity for hypoxanthine (HYP) and inosine (INO) has been observed with correlation coefficients (R(2)) of 0.9987 and 0.9986, respectively. The recoveries of the two ATP derivatives at three different spiked levels ranged from 106.5% to 113.4% for HYP and from 103.1% to 111.2% for INO, with average relative standard deviations lower than 4.2% in both cases. This new method, which is rapid, simple and sensitive, can be used as an alternative tool to conventional tedious methods. PMID:25640126

  14. Lesch-Nyhan syndrome presenting as acute renal failure secondary to obstructive uropathy.

    PubMed

    Ankem, M; Glazier, D B; Barone, J G

    2000-12-20

    Lesch-Nyhan syndrome is a rare genetic disorder characterized by mental retardation, self-mutilation, choreoathetosis, and hyperuricemia. The disease is caused by a mutation in the hypoxanthine-guanine phosphoribosyltransferase gene and is transmitted as a sex-linked recessive disorder. Since hyperuricemia is the primary metabolic problem caused by a hypoxanthine-guanine phosphoribosyltransferase mutation, urologic evaluation and treatment is often necessary for children with this disease. We report a 3-year-old boy who presented with anuric renal failure secondary to bilateral obstructing uric acid calculi. The evaluation of T lymphocytes revealed a hypoxanthine-guanine phosphoribosyltransferase mutation consistent with Lesch-Nyhan syndrome. The diagnosis and urologic management of this disorder is discussed. PMID:11113762

  15. Surface Enhanced Raman Scattering of Whole Human Blood, Blood Plasma and Red Blood Cells: Cellular Processes and Bioanalytical Sensing

    PubMed Central

    Premasiri, W. R.; Lee, J. C.; Ziegler, L. D.

    2013-01-01

    SERS spectra of whole human blood, blood plasma and red blood cells on Au nanoparticle SiO2 substrates excited at 785 nm have been observed. For the sample preparation procedure employed here, the SERS spectrum of whole blood arises from the blood plasma component only. This is in contrast to the normal Raman spectrum of whole blood excited at 785 nm and open to ambient air, which is exclusively due to the scattering of oxyhemoglobin. The SERS spectrum of whole blood shows a storage time dependence that is not evident in the non-SERS Raman spectrum of whole blood. Hypoxanthine, a product of purine degradation, dominates the SERS spectrum of blood after ~10 – 20 hours of storage at 8 °C. The corresponding SERS spectrum of plasma isolated from the stored blood shows the same temporal release of hypoxanthine. Thus, blood cellular components (red blood cells, white blood cells and/or platelets) are releasing hypoxanthine into the plasma over this time interval. The SERS spectrum of red blood cells (RBCs) excited at 785 nm is reported for the first time and exhibits well known heme group marker bands, as well as other bands that may be attributed to cell membrane components or protein denaturation contributions. SERS, as well as normal Raman spectra, of oxy- and met-RBCs are reported and compared. These SERS results can have significant impact in the area of clinical diagnostics, blood supply management and forensics. PMID:22780445

  16. Attenuated Variants of Lesch-Nyhan Disease

    ERIC Educational Resources Information Center

    Jinnah, H. A.; Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David J.; Verdu, Alfonso; Larovere, Laura E.; Chen, Chung-Jen; Cossu, Antonello; Wu, Chien-Hui; Sampat, Radhika; Chang, Shun-Jen; de Kremer, Raquel Dodelson; Nyhan, William; Harris, James C.; Reich, Stephen G.; Puig, Juan G.

    2010-01-01

    Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the…

  17. COMPARISON OF MUTAGENICITY RESULTS FOR NINE COMPOUNDS EVALUATED AT THE HGPRT LOCUS IN THE STANDARD AND SUSPENSION CHO ASSAYS

    EPA Science Inventory

    The Chinese hamster ovary (CHO) assay which measures newly induced mutations at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus has been widely used for mutagenesis testing. he insensitivity of the standard assay to some genotoxic agents has been speculated to be...

  18. MULTIPLE-ENDPOINT MUTAGENESIS WITH CHINESE HAMSTER OVARY (CHO) CELLS: EVALUATION WITH EIGHT CARCINOGENIC AND NON-CARCINOGENIC COMPOUNDS

    EPA Science Inventory

    Using Chinese hamster ovary (CHO) cells in culture, the authors have defined an assay, CHO/HGPRT, to quantify mutagen-induced cytotoxicity and mutations at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus. This assay permits elucidation of the structure-activity r...

  19. Genotoxic effects of sunlight-activated waste water in cultured mammalian cells.

    PubMed

    Strniste, G F; Chen, D J; Okinaka, R T

    1982-07-01

    Cultured Chinese hamster ovary cells were incubated with dilutions of an oil shale retort process water and exposed to nautral sunlight. An enhancement of sevenfold to ninefold was seen in photoinduced cytotoxicity (by a colony-forming assay) and mutagenicity [at the hypoxanthine phosphoribosyltransferase (HPRT) locus] for cells pretreated with the process water compared to effects seen in cells exposed to sunlight only. Significant photoinduced cytotoxicity was also observed in cultured human skin fibroblasts when exposed to the process water before being exposed to near UV (NUV) radiation. The mutation frequencies (determined for the HPRT locus) induced by the process water and NUV radiation were as great as those frequencies seen for far UV light alone. Increases in genotoxicity were observed in excision repair-deficient xeroderma pigmentosum skin fibroblasts when compared to the responses seen in normal cells. Risks to health resulting from the phototransformation of these oil shale retort process waste waters are unassessed at this time. PMID:6954312

  20. A characteristic of mutants induced by the oncogene c-Ha-ras1 and the nature of the mutagenic effect of the oncogene

    SciTech Connect

    Bobrysheva, I.V.; Varshaver, N.B. [Inst. of Molecular Genetics, Moscow (Russian Federation)

    1995-12-01

    Chinese hamster cell clones of independent origin, which were resistant to purine base analogs and induced by the activated c-Ha-ras1 oncogene, were isolated. It was shown that the isolated clones stably retained resistance after cultivation on a medium without an analogy, confirming the mutational nature of the resistance. Most of the clones are able to grow on the HAT medium, retaining partial activity of the hypoxanthine phosphoribosyltransferase enzyme (HPRT); i.e., they are leaky mutants. Analysis by blot-hybridization did not reveal the presence of human ras-sequences in any of the mutants studied. Evidently, the mutagenic action of the oncogene is not insertional, and resistance is not linked to the stably integrated oncogene. The mutagenic effect of c-Ha-ras1 is likely to be of the {open_quotes}hit-and-run{close_quotes} type. 25 refs., 1 fig., 2 tabs.

  1. Small Duplication of HPRT 1 Gene May Be Causative For Lesh-Nyhan Disease in Iranian Patients.

    PubMed

    Boroujerdi, Razieh; Shariati, Mohsen; Naddafnia, Hosein; Rezaei, Hojatolah

    2015-01-01

    Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a rare inborn error of purine metabolism and is characterized by uric acid overproduction along with a variety of neurological manifestations that depend on a degree of the enzymatic deficiency. Inheritance of HPRT deficiency is X-linked recessive; thus, males are generally more affected and heterozygous females are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. More than 300 mutations in the HPRT1 gene have been detected. Diagnosis can be based on clinical and biochemical findings as well as enzymatic and molecular testing. Molecular diagnosis is the best way as it allows for faster and more accurate carrier and prenatal diagnosis. In this report, a new small duplication in the HPRT1 gene was found by sequencing, which has yet to be reported. PMID:25767547

  2. Transport of purines and deoxyadenosine in Escherichia coli.

    PubMed

    Roy-Burman, S; Visser, D W

    1975-12-25

    The characteristics of adenine, guanine, hypoxanthine, xanthine, and uracil uptake in Escherichia coli B show that each base is transported by a specific system. The data support the concept that the transport of guanine, hypoxanthine, xanthine, and uracil function without direct involvement of the respective purine or pyrimidine phosphoribosyltransferase enzymes. Uracil phosphoribosyltransferase is not demonstrable in E. coli B, and large differences are observed in the inhibitory effects of heterologous purines on the uptake of guanine, hypoxanthine, and xanthine as compared to the corresponding inhibitory effects reported for the soluble purine phosphoribosyltransferase enzymes of E. coli B. Additional evidence is provided by the low Km values determined for the transport of adenine, guanine, hypoxanthine, and xanthine relative to the corresponding Km values for the phosphoribosyltransferase enzymes. Data are presented indicating that adenine may be transported without participation of adenine phosphoribosyltransferase. The stimulatory effect of glucose, the inhibitory effect of KCN, and the high intracellular to extracellular concentration gradients of the bases produced in the presence of glucose provide evidence that the transport processes are energy-dependent. The Km values for transport of the purines and uracil range from 10(-7) M to 5 X 10(-7) M. Characteristics of adenine and uracil uptake are similar in E. coli B, E. coli K-12, and a showdomycin-resistant mutant of E. coli B. Adenosine and deoxyadenosine are transported in E. coli B by independent transport systems. Adenine or hypoxanthine does not share the adenosine or deoxyadenosine transport systems as evidence by the mutual lack of competition of free bases and nucleosides on transport. The transport systems for deoxyadenosine and adenosine are defective in the mutant. PMID:1104620

  3. Characterization of a TK6-Bcl-xL gly-159-ala Human Lymphoblast Clone

    SciTech Connect

    Chyall, L.: Gauny, S.; Kronenberg, A.

    2006-01-01

    TK6 cells are a well-characterized human B-lymphoblast cell line derived from WIL-2 cells. A derivative of the TK6 cell line that was stably transfected to express a mutated form of the anti-apoptotic protein Bcl-xL (TK6-Bcl-xL gly-159- ala clone #38) is compared with the parent cell line. Four parameters were evaluated for each cell line: growth under normal conditions, plating efficiency, and frequency of spontaneous mutation to 6?thioguanine resistance (hypoxanthine phosphoribosyl transferase locus) or trifluorothymidine resistance (thymidine kinase locus). We conclude that the mutated Bcl-xL protein did not affect growth under normal conditions, plating efficiency or spontaneous mutation frequencies at the thymidine kinase (TK) locus. Results at the hypoxanthine phosphoribosyl transferase (HPRT) locus were inconclusive. A mutant fraction for TK6?Bcl-xL gly-159-ala clone #38 cells exposed to 150cGy of 160kVp x-rays was also calculated. Exposure to x-irradiation increased the mutant fraction of TK6?Bcl-xL gly-159-ala clone #38 cells.

  4. Monoclonal lupus autoantibody secretion by human-human hybridomas. Selection of hybrids by conventional and novel techniques.

    PubMed Central

    Littman, B H; Muchmore, A V; Steinberg, A D; Greene, W C

    1983-01-01

    Autoantibody-secreting hybridomas were produced by somatic cell fusion of B lymphocytes from a patient with systemic lupus erythematosus with two different human myeloma lines. Selection of hybrids formed from one of these cell lines was performed by using aminopterine-containing culture medium as this cell line was deficient in hypoxanthine-guanine-phosphoribosyl transferase (HGPRT). The second myeloma line was not HGPRT-deficient but instead was treated with diethylpyrocarbonate, which assured death of unfused myeloma cells. This novel technique has wide applicability. Hybridomas were found to secrete antibodies to native DNA and to extractable nuclear antigen. The binding specificities of one IgM anti-DNA antibody was characterized and found to be specific for double-stranded DNA and had particular binding affinity for poly(dG) . poly(dC). PMID:6605979

  5. Dominance of resistance to the alkylating agent 1,2:5,6-dianhydrogalactitol in P388 mouse lymphoma hybrid cells

    Microsoft Academic Search

    István Pályi; Judit Bence; Károly Szikla; Lehel Hullán

    1989-01-01

    Summary Cultured P388\\/S mouse lymphoma cells resistant to 5-bromodeoxyuridine (BUdR) and deficient in thymidine kinase (TK-) were fused with P388\\/DAG cells resistant to 1,2:5,6-dianhydrogalactitol (DAG), an anticancer alkylating agent, and to 6-thioguanine (6-TG) and deficient in hypoxanthine phosphoribosyl-transferase (HPRT-). Sensitivity to DAG in the hybrid line was very close to that in the P388\\/DAG line, which means that resistance to

  6. Lesch–Nyhan disease in a 20-year- old man incorrectly described as developing ‘cerebral palsy’ after general anaesthesia in infancy

    Microsoft Academic Search

    M. A. Chiong; A. Marinaki; J. Duley; B. Bennetts; R. Ouvrier; J. Christodoulou

    2006-01-01

    Summary  Lesch–Nyhan disease (LND) is a rare X-linked recessive genetic disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase\\u000a (HPRT) enzyme. The classic clinical condition is characterized by cognitive impairment, hypotonia at rest, choreoathetosis,\\u000a hyperuricaemia and the hallmark symptom of severe and involuntary self-mutilation. We describe a man with LND who was initially\\u000a thought to have suffered from a dyskinetic cerebral palsy

  7. Molecular Structure of 6-Mercaptopurine

    NSDL National Science Digital Library

    2002-09-12

    Gertrude B. Elion invented 6-mercaptopurine (6MP) in 1954 as a leukemia-fighting drug while she was working on antagonists of nucleic acid building blocks. 6MP is converted to thioinosinic acid by the enzyme hypoxanthine-guanine phosphoribosyltransferase, thus inhibiting RNA synthesis. Mercaptopurine is a drug that is used to treat certain types of cancer and leukemia. There are many side effects to this drug such as reduction of bone marrow, liver function, ulcers, and diarrhea.

  8. Purine oversecretion in cultured murine lymphoma cells deficient in adenylosuccinate synthetase: genetic model for inherited hyperuricemia and gout.

    PubMed Central

    Ullman, B; Wormsted, M A; Cohen, M B; Martin, D W

    1982-01-01

    Alterations in several specific enzymes have been associated with increased rates of purine synthesis de novo in human and other mammalian cells. However, these recognized abnormalities in humans account for only a few percent of the clinical cases of hyperuricemia and gout. We have examined in detail the rates of purine production de novo and purine excretion by normal and by mutant (AU-100) murine lymphoma T cells (S49) 80% deficient in adenylosuccinate synthetase [IMP:L-aspartate ligase (GDP-forming), EC 6.3.4.4]. The intracellular ATP concentration of the mutant cells is slightly diminished, but their GTP is increased 50% and their IMP, four-fold. Compared to wild-type cells, the AU-100 cells excrete into the culture medium 30- to 50-fold greater amounts of purine metabolites consisting mainly of inosine. Moreover, the AU-100 cell line overproduces total purines. In an AU-100-derived cell line, AU-TG50B, deficient in adenylosuccinate synthetase and hypoxanthine/guanine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8), purine nucleoside excretion is increased 50- to 100-fold, and de novo synthesis is even greater than that for AU-100 cells. The overexcretion of purine metabolites by the AU-100 cells seems to be due to the primary genetic deficiency of adenylosuccinate synthetase, a deficiency that requires the cell to increase intracellular IMP in an attempt to maintain ATP levels. As a consequence of elevated IMP pools, large amounts of inosine are secreted into the culture medium. We propose that a similar primary genetic defect may account for the excessive purine excretion in some patients with dominantly inherited hyperuricemia and gout. Images PMID:6957854

  9. Molecular epidemiology studies on occupational and environmental exposure to mutagens and carcinogens, 1997-1999.

    PubMed Central

    Srám, R J; Binková, B

    2000-01-01

    Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure--metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect--chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility--genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens. PMID:10698723

  10. Bacterial delivery of large intact genomic-DNA-containing BACs into mammalian cells

    PubMed Central

    Cheung, Wing; Kotzamanis, George; Abdulrazzak, Hassan; Goussard, Sylvie; Kaname, Tadashi; Kotsinas, Athanassios; Gorgoulis, Vassilis G.; Grillot-Courvalin, Catherine; Huxley, Clare

    2012-01-01

    Efficient delivery of large intact vectors into mammalian cells remains problematical. Here we evaluate delivery by bacterial invasion of two large BACs of more than 150 kb in size into various cells. First, we determined the effect of several drugs on bacterial delivery of a small plasmid into different cell lines. Most drugs tested resulted in a marginal increase of the overall efficiency of delivery in only some cell lines, except the lysosomotropic drug chloroquine, which was found to increase the efficiency of delivery by 6-fold in B16F10 cells. Bacterial invasion was found to be significantly advantageous compared with lipofection in delivering large intact BACs into mouse cells, resulting in 100% of clones containing intact DNA. Furthermore, evaluation of expression of the human hypoxanthine phosphoribosyltransferase (HPRT) gene from its genomic locus, which was present in one of the BACs, showed that single copy integrations of the HPRT-containing BAC had occurred in mouse B16F10 cells and that expression of HPRT from each human copy was 0.33 times as much as from each endogenous mouse copy. These data provide new evidence that bacterial delivery is a convenient and efficient method to transfer large intact therapeutic genes into mammalian cells. PMID:22095052

  11. In Vitro Evaluation of Genotoxic Effects under Magnetic Resonant Coupling Wireless Power Transfer.

    PubMed

    Mizuno, Kohei; Shinohara, Naoki; Miyakoshi, Junji

    2015-01-01

    Wireless power transfer (WPT) technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity. PMID:25853218

  12. Purine salvage pathways among Borrelia species.

    PubMed

    Pettersson, Jonas; Schrumpf, Merry E; Raffel, Sandra J; Porcella, Stephen F; Guyard, Cyril; Lawrence, Kevin; Gherardini, Frank C; Schwan, Tom G

    2007-08-01

    Genome sequencing projects on two relapsing fever spirochetes, Borrelia hermsii and Borrelia turicatae, revealed differences in genes involved in purine metabolism and salvage compared to those in the Lyme disease spirochete Borrelia burgdorferi. The relapsing fever spirochetes contained six open reading frames that are absent from the B. burgdorferi genome. These genes included those for hypoxanthine-guanine phosphoribosyltransferase (hpt), adenylosuccinate synthase (purA), adenylosuccinate lyase (purB), auxiliary protein (nrdI), the ribonucleotide-diphosphate reductase alpha subunit (nrdE), and the ribonucleotide-diphosphate reductase beta subunit (nrdF). Southern blot assays with multiple Borrelia species and isolates confirmed the presence of these genes in the relapsing fever group of spirochetes but not in B. burgdorferi and related species. TaqMan real-time reverse transcription-PCR demonstrated that the chromosomal genes (hpt, purA, and purB) were transcribed in vitro and in mice. Phosphoribosyltransferase assays revealed that, in general, B. hermsii exhibited significantly higher activity than did the B. burgdorferi cell lysate, and enzymatic activity was observed with adenine, hypoxanthine, and guanine as substrates. B. burgdorferi showed low but detectable phosphoribosyltransferase activity with hypoxanthine even though the genome lacks a discernible ortholog to the hpt gene in the relapsing fever spirochetes. B. hermsii incorporated radiolabeled hypoxanthine into RNA and DNA to a much greater extent than did B. burgdorferi. This complete pathway for purine salvage in the relapsing fever spirochetes may contribute, in part, to these spirochetes achieving high cell densities in blood. PMID:17502392

  13. Expression and regulation of INTELECTIN1 in human granulosa-lutein cells: role in IGF-1-induced steroidogenesis through NAMPT.

    PubMed

    Cloix, Lucie; Reverchon, Maxime; Cornuau, Marion; Froment, Pascal; Ramé, Christelle; Costa, Caroline; Froment, Gisèle; Lecomte, Pierre; Chen, Wenyong; Royère, Dominique; Guerif, Fabrice; Dupont, Joëlle

    2014-08-01

    INTELECTIN (ITLN) is an adipokine involved in the regulation of insulin sensitivity and inflammatory and immunity responses. Serum ITLN levels are lower in obese, diabetic, and polycystic ovary syndrome (PCOS) women than in control subjects. ITLN has never been studied in ovarian cells. Here, we identified ITLN1 in human ovarian follicles and investigated the molecular mechanisms involved in the regulation of its expression in response to the insulin sensitizers metformin and rosiglitazone, in human granulosa-lutein cells (hGLCs) and in a human ovarian granulosa-like tumor cell line (KGN). We also studied the effects of human recombinant ITLN1 (hRom1) on steroid production and on the activation of various signaling pathways. Using RT-PCR, immunoblotting, and immunohistochemistry, we found that INTL1 is present in human follicular cells. Using ELISA, we showed that INTL levels are similar in plasma and follicular fluid (FF) in control patients, whereas they are higher in FF than in plasma in PCOS patients. In KGN cells and hGLCs, insulin (10(-8) M), insulin-like growth factor-1 (IGF-1; 10(-8) M), and metformin (10(-2) M or 10(-3) M) increased INTL1 expression (mRNA and protein) after 12 and 24 h of stimulation. For metformin, this effect was mediated by adenosine monophosphate-activated kinase (PRKA). Furthermore, hRom1 increased nicotinamide phosphoribosyltransferase (NAMPT) expression in KGN and hGLCs. We also showed that hRom1 increased IGF-1-induced progesterone and estradiol secretion and this was associated with an increase in the STAR and CYP19A1 protein levels and an increase in IGF-1R signaling. Furthermore, all these data were abolished when NAMPT was knocked down in KGN cells, suggesting that INTL1 improves IGF-1-induced steroidogenesis through induction of NAMPT in hGLCs. PMID:24943040

  14. EGFR Intron Recombination in Human Gliomas: Inappropriate Diversion of V(D)J Recombination?

    PubMed Central

    Fenstermaker, Robert A; Ciesielski, Michael J

    2007-01-01

    The epidermal growth factor receptor (EGFR) is a membrane-bound, 170 kDa, protein tyrosine kinase that plays an important role in tumorigenesis. The EGFR gene, which is composed of over 168 kb of sequence, including a 123-kb first intron, is frequently amplified and rearranged in malignant gliomas leading to the expression of oncogenic deletion (DM) and tandem duplication (TDM) mutants. The most common DM in gliomas is EGFRvIII, which arises from recombination between introns 1 and 7 with deletion of exons 2 through 7 and intervening introns. In addition, some human gliomas express 180- to 190-kDa TDM, which are constitutively active and highly oncogenic. Both DM and TDM arise by recombination of introns that contain sequences with homology to the recombination signal sequence (RSS) heptamers and nonamers present in the V(D)J region of the immunoglobin and T lymphocyte antigen receptor genes. V(D)J RSS have also been identified in certain proto-oncogenes like bcl-2 that are involved in translocations associated with the development of human lymphomas and in other genes such as hypoxanthine-guainine phosphoribosyl transferase (HPRT) in which deletion mutations and intron rearrangements are a common phenomenon. Together with the expression of recombination associated gene (RAG) and nonhomologous end-joining (NHEJ) proteins in gliomas, these observation suggest that aberrant activity of the V(D)J recombinase may be involved in the activation of proto-oncogenes in both liquid and solid tumors. PMID:18645600

  15. Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

    PubMed Central

    Ichida, Kimiyoshi; Amaya, Yoshihiro; Okamoto, Ken; Nishino, Takeshi

    2012-01-01

    Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD+ or O2. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors. PMID:23203137

  16. Crucial involvement of xanthine oxidase in the intracellular signalling networks associated with human myeloid cell function

    PubMed Central

    Abooali, Maryam; Lall, Gurprit S.; Coughlan, Karen; Lall, Harjinder S.; Gibbs, Bernhard F.; Sumbayev, Vadim V.

    2014-01-01

    Xanthine oxidase (XOD) is an enzyme which plays a central role in purine catabolism by converting hypoxanthine into xanthine and then further into uric acid. Here we report that XOD is activated in THP-1 human myeloid cells in response to pro-inflammatory and growth factor stimulation. This effect occurred following stimulation of THP-1 cells with ligands of plasma membrane associated TLRs 2 and 4, endosomal TLRs 7 and 8 as well as stem cell growth factor (SCF). Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) transcription complexes were found to be responsible for XOD upregulation. Importantly, the mammalian target of rapamycin (mTOR), a major myeloid cell translation regulator, was also found to be essential for XOD activation. Specific inhibition of XOD by allopurinol and sodium tungstate led to an increase in intracellular AMP levels triggering downregulation of mTOR activation by phosphorylation of its T2446 residue. Taken together, our results demonstrate for the first time that XOD is not only activated by pro-inflammatory stimuli or SCF but also plays an important role in maintaining mTOR-dependent translational control during the biological responses of human myeloid cells. PMID:25200751

  17. The Human Homolog of Escherichia coli Endonuclease V Is a Nucleolar Protein with Affinity for Branched DNA Structures

    PubMed Central

    Laerdahl, Jon K.; Gran Neurauter, Christine; Heggelund, Julie E.; Thorgaard, Eirik; Strøm-Andersen, Pernille; Bjørås, Magnar; Dalhus, Bjørn; Alseth, Ingrun

    2012-01-01

    Loss of amino groups from adenines in DNA results in the formation of hypoxanthine (Hx) bases with miscoding properties. The primary enzyme in Escherichia coli for DNA repair initiation at deaminated adenine is endonuclease V (endoV), encoded by the nfi gene, which cleaves the second phosphodiester bond 3? of an Hx lesion. Endonuclease V orthologs are widespread in nature and belong to a family of highly conserved proteins. Whereas prokaryotic endoV enzymes are well characterized, the function of the eukaryotic homologs remains obscure. Here we describe the human endoV ortholog and show with bioinformatics and experimental analysis that a large number of transcript variants exist for the human endonuclease V gene (ENDOV), many of which are unlikely to be translated into functional protein. Full-length ENDOV is encoded by 8 evolutionary conserved exons covering the core region of the enzyme, in addition to one or more 3?-exons encoding an unstructured and poorly conserved C-terminus. In contrast to the E. coli enzyme, we find recombinant ENDOV neither to incise nor bind Hx-containing DNA. While both enzymes have strong affinity for several branched DNA substrates, cleavage is observed only with E. coli endoV. We find that ENDOV is localized in the cytoplasm and nucleoli of human cells. As nucleoli harbor the rRNA genes, this may suggest a role for the protein in rRNA gene transactions such as DNA replication or RNA transcription. PMID:23139746

  18. Effects of 8-aminoguanosine and 2'-deoxyguanosine on the human mixed lymphocyte reaction (MLR). I. Description of the inhibition

    SciTech Connect

    Scott, M.E.; Gilbertsen, R.B.

    1986-03-05

    Patients deficient in purine nucleoside phosphorylase (PNP) generally have a pronounced deficiency in T cell function with no deleterious effect on B cell function. It has been demonstrated that high concentrations of 8-amino-guanosine (8-AG), an inhibitor of PNP, in combination with the PNP substrate 2'-deoxyguanosine (dGuo) can inhibit mitogen and antigen responsiveness of human lymphocytes in culture. The studies described here evaluated the effects of 8-AG and dGuo on the human MLR. Normal human lymphocytes were isolated from venous blood using Ficoll-Hypaque gradients. Stimulator cells, pretreated with mitomycin C (50 ..mu..g/ml), were added with an equal number of responder cells (2 x 10/sup 5/) to the wells of flat-bottomed microtiter plates. Cell proliferation was quantitated by the uptake of /sup 3/H-thymidine (TdR) during the final 4 hrs of six-day cultures. dGuo at 10-50 ..mu..M had no effect or stimulated proliferation, while dGuo at > 75 ..mu..M was markedly inhibitory. 8-AG alone at 100 ..mu..M had essentially no effect on TdR uptake. 8-AG (10-100 ..mu..M) plus dGuo (50 ..mu..M) produced a concentration-dependent inhibition of the MLR resulting in 8-AG IC/sub 50/s generally < 60 ..mu..M. Coaddition of 50 ..mu..M 2'-deoxycytidine, hypoxanthine or adenine partially prevented inhibition of the MLR.

  19. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans.

    PubMed

    Cai, Weijing; Uribarri, Jaime; Zhu, Li; Chen, Xue; Swamy, Shobha; Zhao, Zhengshan; Grosjean, Fabrizio; Simonaro, Calogera; Kuchel, George A; Schnaider-Beeri, Michal; Woodward, Mark; Striker, Gary E; Vlassara, Helen

    2014-04-01

    Age-associated dementia and Alzheimer's disease (AD) are currently epidemic. Neither their cause nor connection to the metabolic syndrome (MS) is clear. Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense, is a central feature of AD. Age-related MS and diabetes are also causally associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced glycation end products (AGEs)]. Changes in the modern diet include excessive nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three diets throughout life: low-AGE (MG(-)), MG-supplemented low-AGE (MG(+)), and regular (Reg) chow. Older MG(+)-fed mice, similar to old Reg controls, developed MS, increased brain amyloid-?42, deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotinamide phosphoribosyltransferase, AGE receptor 1, and PPAR?. These changes were not due to aging or caloric intake, as neither these changes nor the MS were present in age-matched, pair-fed MG(-) mice. The mouse data were enhanced by significant temporal correlations between high circulating AGEs and impaired cognition, as well as insulin sensitivity in older humans, in whom dietary and serum MG levels strongly and inversely associated with SIRT1 gene expression. The data identify a specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and inflammation. Because SIRT1 deficiency in humans is both preventable and reversible by AGE reduction, a therapeutic strategy that includes AGE reduction may offer a new strategy to combat the epidemics of AD and MS. PMID:24567379

  20. Membrane permeation characteristics of abacavir in human erythrocytes and human T-lymphoblastoid CD4+ CEM cells: comparison with (-)-carbovir.

    PubMed

    Mahony, William B; Domin, Barbara A; Daluge, Susan M; Zimmerman, Thomas P

    2004-11-01

    Abacavir, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol, is a novel purine carbocyclic nucleoside analogue that has been approved by the FDA for the treatment of HIV (as Ziagen trade mark [abacavir sulfate]). Chemically, abacavir and (-)-carbovir (CBV) differ only at the 6-position of the purine ring; abacavir contains a cyclopropylamino moiety in place of the 6-lactam functionality of CBV. Intracellularly both are ultimately metabolized to CBV triphosphate. We compared the membrane permeation characteristics of these two compounds at 20 degrees C in human erythrocytes and in human T-lymphoblastoid CD4+ CEM cells, using a "papaverine-stop" assay. In erythrocytes, abacavir influx was rapid, nonsaturable (rate constant=200 pmol/s/mM/microl cell water), and unaffected by inhibitors of nucleoside or nucleobase transport. CBV influx was slow, saturable, strongly inhibited by adenine or hypoxanthine, and occurred via both the nucleobase carrier (Vmax=0.67 pmol/s/microl cell water; Km=50 microM) and the nucleoside carrier (Vmax=0.47 pmol/s/microl cell water; Km=440 microM). Similar qualitative results were obtained with CD4+ CEM cells, although CBV influx rates were somewhat higher and abacavir influx rates lower, compared to the corresponding rates in erythrocytes. Equilibrium studies further revealed that both compounds are concentrated intracellularly, but nonmetabolically, in both cell types, apparently due to cytosolic protein binding (absent in erythrocyte ghosts). We conclude that, in both cell types, while CBV influx is slow and carrier-dependent, abacavir influx occurs rapidly by nonfacilitated diffusion. The membrane permeation characteristics of abacavir are consistent with its superior oral bioavailability and its impressive ability to penetrate the central nervous system. PMID:15450945

  1. Attenuated variants of Lesch-Nyhan disease

    PubMed Central

    Ceballos-Picot, Irene; Torres, Rosa J.; Visser, Jasper E.; Schretlen, David J.; Verdu, Alfonso; Laróvere, Laura E.; Chen, Chung-Jen; Cossu, Antonello; Wu, Chien-Hui; Sampat, Radhika; Chang, Shun-Jen; de Kremer, Raquel Dodelson; Nyhan, William; Harris, James C.; Reich, Stephen G.; Puig, Juan G.

    2010-01-01

    Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency. PMID:20176575

  2. Ribavirin uptake by human erythrocytes and the involvement of nitrobenzylthioinosine-sensitive (es)-nucleoside transporters.

    PubMed

    Jarvis, S M; Thorn, J A; Glue, P

    1998-04-01

    1. The major toxicity associated with oral therapy with ribavirin is anaemia, which has been postulated to occur as a result of accumulation of ribavirin triphosphate interfering with erythrocyte respiration. The objective of this study was to determine the mechanism by which ribavirin enters into erythrocytes. 2. Entry into human erythrocytes was examined by measuring influx rates of [3H]-ribavirin alone and with the inhibitor nitrobenzylthioinosine (NBMPR), and by investigating the inhibitory effects of nucleoside and nucleobase permeants on ribavirin transport, by use of inhibitor oil-stop methods. Transport mechanisms were further characterized by assessment of substrates to cause countertransport of ribavirin in preloaded erythrocytes, and by measuring the effects of ribavirin on [3H]-NBMPR binding to erythrocyte membranes. 3. Human erythrocytes had a saturable influx mechanism for ribavirin (Km at 22 degrees C of 440+/-100 microM) which was inhibited by nanomolar concentrations of NBMPR (IC50 0.99+/-0.15 nM). Nucleosides also inhibited the influx of ribavirin (adenosine more effective than uridine) but the nucleobases hypoxanthine and adenine had no effect. In addition, uridine caused the countertransport of ribavirin in human erythrocytes. Entry of ribavirin into horse erythrocytes, a cell type that lacks the NBMPR-sensitive (es) nucleoside transporter, proceeded slowly and via a pathway that was resistant to NBMPR inhibition. Ribavirin was a competitive inhibitor of adenosine influx (mean Ki 0.48+/-0.14 mM) and also inhibited NBMPR binding to erythrocyte membranes (mean Ki 2.2+/-0.39 mM). 4. These data indicate that ribavirin is a transported permeant for the es nucleoside transporter of human erythrocytes. There was no evidence for ribavirin entering cells via a nucleobase transporter. PMID:9605565

  3. Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families.

    PubMed Central

    Suchi, M; Mizuno, H; Kawai, Y; Tsuboi, T; Sumi, S; Okajima, K; Hodgson, M E; Ogawa, H; Wada, Y

    1997-01-01

    Uridine monophosphate (UMP) synthase is a bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC). Loss of either enzymatic activity results in hereditary orotic aciduria, a rare autosomal recessive disorder characterized by retarded growth, anemia, and excessive urinary excretion of orotic acid. We have isolated the UMP synthase chromosomal gene from a lambdaEMBL-3 human genomic library and report a single-copy gene spanning approximately 15 kb. The UMP synthase genomic structure encodes six exons ranging in size from 115 bp to 672 bp, and all splicing junctions adhere to the canonical GT/AG rule. Cognate promoter elements implicated in glucocorticoid- and cAMP-mediated regulation as well as in liver-, myeloid-, and lymphocyte-specific expression are located within the 5' flanking sequence. Molecular investigation of UMP synthase deficiency in a Japanese orotic aciduria patient revealed mutations R96G (A-to-G transition; nt 286) and G429R (G-to-C transversion; nt 1285) in one allele and V109G (T-to-G transversion; nt 326) in the other allele. Expression of human UMP synthase cDNAs containing these mutations in pyrimidine auxotrophic Escherichia coli and in recombinant baculovirus-infected Sf21 cells demonstrates impaired activity presumably associated with the urinary orotic acid substrate accumulations observed in vivo. We further establish the identity of two polymorphisms, G213A (v = .26) and 440Gpoly (v = .27) located in exons 3 and 6, respectively, which did not significantly compromise either OPRT or ODC function. Images Figure 1 Figure 4 Figure 5 PMID:9042911

  4. NAD+ Levels Control Ca2+ Store Replenishment and Mitogen-induced Increase of Cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 Channel Gating in Human T Lymphocytes*

    PubMed Central

    Magnone, Mirko; Bauer, Inga; Poggi, Alessandro; Mannino, Elena; Sturla, Laura; Brini, Marisa; Zocchi, Elena; De Flora, Antonio; Nencioni, Alessio; Bruzzone, Santina

    2012-01-01

    Intracellular NAD+ levels ([NAD+]i) are important in regulating human T lymphocyte survival, cytokine secretion, and the capacity to respond to antigenic stimuli. NAD+-derived Ca2+-mobilizing second messengers, produced by CD38, play a pivotal role in T cell activation. Here we demonstrate that [NAD+]i modifications in T lymphocytes affect intracellular Ca2+ homeostasis both in terms of mitogen-induced [Ca2+]i increase and of endoplasmic reticulum Ca2+ store replenishment. Lowering [NAD+]i by FK866-mediated nicotinamide phosphoribosyltransferase inhibition decreased the mitogen-induced [Ca2+]i rise in Jurkat cells and in activated T lymphocytes. Accordingly, the Ca2+ content of thapsigargin-sensitive Ca2+ stores was greatly reduced in these cells in the presence of FK866. When NAD+ levels were increased by supplementing peripheral blood lymphocytes with the NAD+ precursors nicotinamide, nicotinic acid, or nicotinamide mononucleotide, the Ca2+ content of thapsigargin-sensitive Ca2+ stores as well as cell responsiveness to mitogens in terms of [Ca2+]i elevation were up-regulated. The use of specific siRNA showed that the changes of Ca2+ homeostasis induced by NAD+ precursors are mediated by CD38 and the consequent ADPR-mediated TRPM2 gating. Finally, the presence of NAD+ precursors up-regulated important T cell functions, such as proliferation and IL-2 release in response to mitogens. PMID:22547068

  5. ‘Human, Still Human

    Microsoft Academic Search

    Jérôme Bindé

    2005-01-01

    For more than a century the shifts in western thought have witnessed: the death of God, the demise of political ideologies that appeared to have taken over from ‘divine’ values, and the solitude of the disoriented individual. The individual’s malaise may be the symptom of a questioning of the very notion of being human. Adopting the critique of humanism introduced

  6. Genotoxicity of 2,6- and 3,5-Dimethylaniline in Cultured Mammalian Cells: The Role of Reactive Oxygen Species

    PubMed Central

    Chao, Ming-Wei; Kim, Min Young; Wogan, Gerald N.

    2012-01-01

    Several alkylanilines with structures more complex than toluidines have been associated epidemiologically with human cancer. Their mechanism of action remains largely undetermined, and there is no reported evidence that it replicates that of multicyclic aromatic amines even though the principal metabolic pathways of P450-mediated hydroxylation and phase II conjugation are very similar. As a means to elucidate their mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt +/?) gene induced in several Chinese hamster ovary cell types by 2,6- and 3,5-dimethylaniline (2,6-DMA, 3,5-DMA) and their N- and ring-hydroxyl derivatives (N-OH-2,6-DMA, N-OH-3,5-DMA, 2,6-DMAP, 3,5-DMAP) were assessed. Dose-response relationships were determined in the parental AA8 cell line, its repair-deficient UV5 subclone and other repair-deficient 5P3NAT2 or -proficient 5P3NAT2R9 subclones engineered to express mouse cytochrome P4501A2 (CYP1A2) and human N-acetyltransferase (NAT2), and also in AS52 cells harboring the bacterial guanine-hypoxanthine phosphoribosyltransferase (gpt) gene. Mutations in the gpt gene of AS52 cells were characterized and found to be dominated by G:C to A:T and A:T to G:C transitions. Separately, treatment of AS52 cells with N-OH-2,6-DMA, N-OH-3,5-DMA, 2,6-DMAP, 3,5-DMAP, and 3,5-DMAP led to intracellular production of reactive oxygen species (ROS) for at least 24h after removal of the mutagens in every case. Using the comet assay, DNA strand breaks were observed in a dose-dependent manner in AS52 cells when treated with each of the four N-OH-2,6-DMA, N-OH-3,5-DMA, 2,6-DMAP, and 3,5-DMAP derivatives. Comparative evaluation of the results indicates that the principal mechanism of mutagenic action is likely to be through redox cycling of intracellularly bound aminophenol/quinone imine structures to generate ROS rather than through formation of covalent DNA adducts. PMID:22831970

  7. Adenosine transport in peripheral blood lymphocytes from Lesch-Nyhan patients.

    PubMed Central

    Torres, Rosa J; Deantonio, Isabel; Prior, Carmen; Puig, Juan G

    2004-01-01

    We postulated that adenosine function could be related to some of the neurological features of Lesch-Nyhan syndrome and therefore characterized adenosine transport in PBLs (peripheral blood lymphocytes) obtained from Lesch-Nyhan patients (PBL(LN)) and from controls (PBL(C)). Adenosine transport was significantly lower in PBL(LN) when compared with that in PBL(C) and a significantly lower number of high affinity sites for [(3)H]nitrobenzylthioinosine binding were quantified per cell ( B (max)) in PBL(LN) when compared with that in PBL(C). After incubation with 25 microM hypoxanthine, adenosine transport was significantly decreased in PBL(LN) with respect to PBL(C). Hypoxanthine incubation lowers [(3)H]nitrobenzylthioinosine binding in PBL(C), with respect to basal conditions, but does not affect it in PBL(LN). This indicates that hypoxanthine affects adenosine transport in control and hypoxanthine-guanine phosphoribosyltransferase-deficient cells by different mechanisms. PMID:14572307

  8. Fossil humans 1 Fossil humans

    E-print Network

    Delson, Eric

    , and close extinct rel- atives) recognizes the family Hylobatidae for the gib- bons and Hominidae for humansFossil humans 1 Fossil humans All prehistoric skeletal remains of humans which are archeologically, anatomically modern humans. In this sense, the term "humans" is used broadly to mean all primates related

  9. Silencing expression of the catalytic subunit of DNA-dependent protein kinase by small interfering RNA sensitizes human cells for radiation-induced chromosome damage, cell killing, and mutation

    NASA Technical Reports Server (NTRS)

    Peng, Yuanlin; Zhang, Qinming; Nagasawa, Hatsumi; Okayasu, Ryuichi; Liber, Howard L.; Bedford, Joel S.

    2002-01-01

    Targeted gene silencing in mammalian cells by RNA interference (RNAi) using small interfering RNAs (siRNAs) was recently described by Elbashir et al. (S. M. Elbashir et al., Nature (Lond.), 411: 494-498, 2001). We have used this methodology in several human cell strains to reduce expression of the Prkdc (DNA-PKcs) gene coding for the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) that is involved in the nonhomologous end joining of DNA double-strand breaks. We have also demonstrated a radiosensitization for several phenotypic endpoints of radiation damage. In low-passage normal human fibroblasts, siRNA knock-down of DNA-PKcs resulted in a reduced capacity for restitution of radiation-induced interphase chromosome breaks as measured by premature chromosome condensation, an increased yield of acentric chromosome fragments at the first postirradiation mitosis, and an increased radiosensitivity for cell killing. For three strains of related human lymphoblasts, DNA-PKcs-targeted siRNA transfection resulted in little or no increase in radiosensitivity with respect to cell killing, a 1.5-fold decrease in induced mutant yield in TK6- and p53-null NH32 cells, but about a 2-fold increase in induced mutant yield in p53-mutant WTK1 cells at both the hypoxanthine quanine phosphoribosyl transferase (hprt) and the thymidine kinase loci.

  10. Human Trafficking

    MedlinePLUS

    ... fraud, or coercion for the purpose of commercial sex, debt bondage, or forced labor. They are young children, teenagers, men and ... them. Human Trafficking vs. Human Smuggling Victims are forced, ... Individuals consent to being smuggled. Human trafficking is ...

  11. Human bites

    MedlinePLUS

    Bites - human ... Human bites that break the skin, like all puncture wounds, have a high risk of infection. They ... bite to express anger or other negative feelings. Human bites may be more dangerous than most animal ...

  12. Human Ecology Human ecology Research

    E-print Network

    Wang, Z. Jane

    Human Ecology Impact of Human ecology Research Bonus Issue FROM SCHOLARSHIP TO POLICY MAKING OF HUMAN ECOLOGY APRIL 2005/VOLUME 33, NUMBER 1 #12;Human Ecology Volume 33, Number 1 April 2005 The New York State College of Human Ecology at Cornell University Lisa Staiano-Coico, Ph.D. Rebecca Q

  13. Humanity and human DNA.

    PubMed

    Mattei, Jean-François

    2012-10-01

    Genetics has marked the second half of the 20th century by addressing such formidable problems as the identification of our genes and their role, their interaction with the environment, and even their therapeutic uses. The identification of genes raises questions about differences between humans and non-humans, as well as about the evolution towards trans-humanism and post-humanism. In practise, however, the main question concerns the limits of prenatal genetic diagnosis, not only on account of the seriousness of the affections involved but also because of the choice to be made between following-up the medical indication and engaging in a systematic public health strategy aimed at eliminating children with certain handicaps. History reminds us that genetic science has already been misused by political forces influenced by the ideas of eugenics, particularly in the Nazi period. We may wonder whether it is reasonable to formulate a judgement on the life of a child yet to be born, merely on the basis of a DNA analysis. My experience as a practising geneticist and my involvement in French politics forces me to stress the dangers of a new eugenics hiding behind a medical mask. As demonstrated by epigenetics, human beings cannot be reduced to their DNA alone. In our society, one of the problems concerns individuals whose lives may be considered by some as simply not worth living. Another problem is the place and the social significance of the handicapped amongst us. Fortunately, recent progresses in gene therapy, biotherapy, and even pharmacology, appear to be opening up promising therapeutic perspectives. We should bear in mind that the chief vocation of medical genetics, which fully belongs to the art of medicine, is to heal and to cure. This is precisely where genetics should concentrate its efforts software. PMID:22705070

  14. Description and partial characterization of a nucleolar RNA-associated autoantigen defined by a human monoclonal antibody

    PubMed Central

    1987-01-01

    B lymphocytes from a patient with systemic lupus erythematosus (SLE) and several circulating autoantibodies (including antinucleolar antibodies) were immortalized by fusion with a hypoxanthine/guanine phosphoribosyl transferase (HGPRT)-deficient human B cell line. Multiple human monoclonal antibodies (mAb) were obtained which, in solid-phase enzyme immunoassay, were reactive with DNA. One mAb was of special interest because it reacted strongly with both single-stranded DNA and an extractable nuclear antigen found in rabbit thymus extract (RTE). In an immunofluorescent assay using fixed human cells, the latter mAb also bound predominantly to cell nucleoli. A combination of enzyme digestion and metabolic inhibitor studies of the target cells in this immunofluorescent assay suggested that the antigen(s) bound by the mAb was an RNA-associated protein or a ribonucleoprotein that is distinct from intact RNA polymerase I and not associated with the transcriptional units of the nucleolus. In other experiments, using fractions of RTE isolated by ion-exchange chromatography, the antigens bound by the mAb were shown to be highly negatively charged molecules. Immunoprecipitation and SDS-PAGE analyses of labeled cell extracts bound by the mAb revealed a doublet of 17 and 18 kD. Since the original patient's serum autoantibodies also bound to both an RNase-sensitive, acidic, extractable nuclear antigen and to nucleoli, and immunoprecipitated proteins of similar molecular masses in SDS-PAGE, it appears that the described mAb is a product of an immortalized autoantibody-producing B cell clone from the SLE patient's peripheral blood. This mAb probably defines a novel RNA-associated autoantigen residing predominantly in the nucleolus or, less likely, a variant of either RNA polymerase I or the ribosomal autoantigens (P proteins). PMID:2435834

  15. Genetic Manipulation in ?ku80 Strains for Functional Genomic Analysis of Toxoplasma gondii

    PubMed Central

    Rommereim, Leah M.; Hortua Triana, Miryam A.; Falla, Alejandra; Sanders, Kiah L.; Guevara, Rebekah B.; Bzik, David J.; Fox, Barbara A.

    2013-01-01

    Targeted genetic manipulation using homologous recombination is the method of choice for functional genomic analysis to obtain a detailed view of gene function and phenotype(s). The development of mutant strains with targeted gene deletions, targeted mutations, complemented gene function, and/or tagged genes provides powerful strategies to address gene function, particularly if these genetic manipulations can be efficiently targeted to the gene locus of interest using integration mediated by double cross over homologous recombination. Due to very high rates of nonhomologous recombination, functional genomic analysis of Toxoplasma gondii has been previously limited by the absence of efficient methods for targeting gene deletions and gene replacements to specific genetic loci. Recently, we abolished the major pathway of nonhomologous recombination in type I and type II strains of T. gondii by deleting the gene encoding the KU80 protein1,2. The ?ku80 strains behave normally during tachyzoite (acute) and bradyzoite (chronic) stages in vitro and in vivo and exhibit essentially a 100% frequency of homologous recombination. The ?ku80 strains make functional genomic studies feasible on the single gene as well as on the genome scale1-4. Here, we report methods for using type I and type II ?ku80?hxgprt strains to advance gene targeting approaches in T. gondii. We outline efficient methods for generating gene deletions, gene replacements, and tagged genes by targeted insertion or deletion of the hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) selectable marker. The described gene targeting protocol can be used in a variety of ways in ?ku80 strains to advance functional analysis of the parasite genome and to develop single strains that carry multiple targeted genetic manipulations. The application of this genetic method and subsequent phenotypic assays will reveal fundamental and unique aspects of the biology of T. gondii and related significant human pathogens that cause malaria (Plasmodium sp.) and cryptosporidiosis (Cryptosporidium). PMID:23892917

  16. A study of allelic polymorphism of four short tandem repeats in the population of northwestern Russia

    SciTech Connect

    Aseev, M.V.; Skakun, V.N.; Baranov, V.S. [Ott Institute of Obstetrics and Gynecology, St. Petersburg (Russian Federation)

    1995-06-01

    Characteristics of the allelic polymorphisms of the trimeric AGC repeat of the androgen receptor gene (Xq11-12), exon 1 (AR); the tetrameric ATCT repeat of the von Willebrand factor gene (12p12), intron 40 (vWF); the AGAT repeat of the hypoxanthine phosphoribosyltransferase gene (Xq26) (HPRT); and the AGAT repeat of anonymous DNA sequences of the short arm of chromosome X (STRX1) were studied in 160 DNA samples from unrelated inhabitants of northwestern Russia using the method of polymerase chain reaction. Seventeen, ten, eight, and nine alleles were revealed electrophoretically for short tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The heterozygosity indices for these repeats were 0.80, 0.70, 0.54, and 0.58, respectively. The values for AR and vWF correlated with those expected according to the Hardy-Weinberg equilibrium, whereas the values for HPRT and STRX1 differed significantly from those theoretically expected. The individualization potentials were 0.045, 0.135, 0.095, and 0.061 for the short tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The distribution of genotypes for the set of these four loci in the population studied was determined. The possibilities of using the studied polymorphic marker systems in molecular diagnosis of the corresponding monogenic diseases - spinal and bulbar muscle atrophy (AR), Lesch-Nyhan disease (HPRT), and von Willebrand disease (vWF) - as well as in population human genetics, testing of personal identity, and molecular approaches to the estimation of mutagenic activity are discussed. 17 refs., 2 figs., 6 tabs.

  17. Severe pyridine nucleotide depletion in fibroblasts from Lesch-Nyhan patients.

    PubMed Central

    Fairbanks, Lynette D; Jacomelli, Gabriella; Micheli, Vanna; Slade, Tina; Simmonds, H Anne

    2002-01-01

    The relationship between a complete deficiency of the purine enzyme hypoxanthine-guanine phosphoribosyltransferase and the neurobehavioural abnormalities in Lesch-Nyhan disease remains an enigma. In vitro studies using lymphoblasts or fibroblasts have evaluated purine and pyrimidine metabolism with conflicting results. This study focused on pyridine nucleotide metabolism in control and Lesch-Nyhan fibroblasts using radiolabelled salvage precursors to couple the extent of uptake with endocellular nucleotide concentrations. The novel finding, highlighted by specific culture conditions, was a marked NAD depletion in Lesch-Nyhan fibroblasts. ATP and GTP were also 50% of the control, as reported in lymphoblasts. A 6-fold greater incorporation of [(14)C]nicotinic acid into nicotinic acid- adenine dinucleotide by Lesch-Nyhan fibroblasts, with no unmetabolized substrate (20% in controls), supported disturbed pyridine metabolism, NAD depletion being related to utilization by poly(ADP-ribose) polymerase in DNA repair. Although pyrimidine nucleotide concentrations were similar to controls, Lesch-Nyhan cells showed reduced [(14)C]cytidine/uridine salvage into UDP sugars. Incorporation of [(14)C]uridine into CTP by both was minimal, with more than 50% [(14)C]cytidine metabolized to UTP, indicating that fibroblasts, unlike lymphoblasts, lack active CTP synthetase, but possess cytidine deaminase. Restricted culture conditions may be neccesary to mimic the situation in human brain cells at an early developmental stage. Cell type may be equally important. NAD plus ATP depletion in developing brain could restrict DNA repair, leading to neuronal damage/loss by apoptosis, and, with GTP depletion, affect neurotransmitter synthesis and basal ganglia dopaminergic neuronal systems. Thus aberrant pyridine nucleotide metabolism could play a vital role in the pathophysiology of Lesch-Nyhan disease. PMID:11996669

  18. The Human Spark: Being Human

    NSDL National Science Digital Library

    2012-06-12

    This lesson plan from PBS covers a variety of biology topics related to the human as an animal. Students will view and discuss segments from the PBS program The Human Spark. In the first learning activity, the class will explore how human thought differs from that of other species. In the second learning activity, students will examine different traits and abilities, how these abilities have evolved to help humans deal with their environment, and how they distinguish humans from other animals.

  19. Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

    NASA Technical Reports Server (NTRS)

    Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

    1994-01-01

    The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

  20. A novel method for measuring the ATP-related compounds in human erythrocytes.

    PubMed

    Aragon-Martinez, Othoniel Hugo; Galicia, Othir; Isiordia-Espinoza, Mario Alberto; Martinez-Morales, Flavio

    2014-01-01

    The ATP-related compounds in whole blood or red blood cells have been used to evaluate the energy status of erythrocytes and the degradation level of the phosphorylated compounds under various conditions, such as chronic renal failure, drug monitoring, cancer, exposure to environmental toxics, and organ preservation. The complete interpretation of the energetic homeostasis of erythrocytes is only performed using the compounds involved in the degradation pathway for adenine nucleotides alongside the uric acid value. For the first time, we report a liquid chromatographic method using a diode array detector that measures all of these compounds in a small human whole blood sample (125 ?L) within an acceptable time of 20 min. The stability was evaluated for all of the compounds and ranged from 96.3 to 105.1% versus the day zero values. The measurement had an adequate sensitivity for the ATP-related compounds (detection limits from 0.001 to 0.097 ?mol/L and quantification limits from 0.004 to 0.294 ?mol/L). This method is particularly useful for measuring inosine monophosphate, inosine, hypoxanthine, and uric acid. Moreover, this assay had acceptable linearity (r > 0.990), precision (coefficients of variation ranged from 0.1 to 2.0%), specificity (similar retention times and spectra in all samples) and recoveries (ranged from 89.2 to 104.9%). The newly developed method is invaluable for assessing the energetic homeostasis of red blood cells under diverse conditions, such as in vitro experiments and clinical settings. PMID:25048613

  1. Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

    NASA Astrophysics Data System (ADS)

    Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

    1994-10-01

    The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/?m to 975 KeV/gmm with particle energy (on the cells) between 94 - 603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/?m. The inactivation cross-section (?i) and the action-section for mutant induction (?m) ranged from 2.2 to 92.0 ?m2 and 0.09 to 5.56 × 10-3 ?m2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/?m. The mutagenicity (?m/?i) ranged from 2.05 to 7.99 × 10-5 with the maximum value at 150 keV/?m. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

  2. Human microbiomics

    Microsoft Academic Search

    J. Rajendhran; P. Gunasekaran

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide\\u000a study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and\\u000a health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity\\u000a has

  3. Human Evolution

    NSDL National Science Digital Library

    MacEvoy, Bruce

    This resource from Bruce MacEvoy links to documents "summarizing the hominid fossil record and hypothesized lines of human evolution from 5 million years ago to the present." The site is divided into five parts: Chart of Human Evolution, Tour of the Human Fossil Record, The Hominid Brain, Hominid Tools, Hominid Fossil Sites and Patterns of Hominid Dispersal.

  4. College of Humanities College of Humanities

    E-print Network

    Kim, Panki

    58 59 30 31 College of Humanities College of Humanities College of Humanities College of Humanities College of Humanities College of Humanities College of Humanities College of Humanities College of Humanities College of Social Sciences College of Natural Sciences College of Natural Sciences College

  5. Humanized mice

    PubMed Central

    Macchiarini, Francesca; Manz, Markus G.; Palucka, A. Karolina; Shultz, Leonard D.

    2005-01-01

    Animal models have been instrumental in increasing the understanding of human physiology, particularly immunity. However, these animal models have been limited by practical considerations and genetic diversity. The creation of humanized mice that carry partial or complete human physiological systems may help overcome these obstacles. The National Institute of Allergy and Infectious Diseases convened a workshop on humanized mouse models for immunity in Bethesda, MD, on June 13–14, 2005, during which researchers discussed the benefits and limitations of existing animal models and offered insights into the development of future humanized mouse models. PMID:16301740

  6. Human Anatomy

    NSDL National Science Digital Library

    Ms. Schultz

    2007-11-09

    Please find links below: Human Anatomy Human Anatomy Online Human Body - Gray s Anatomy - Digestive Aparatus MEDtropolis - Virtual Body - can be viewed in English or Spanish. Contains tours of the Human Brain, Skeleton, Human Heart, and Digestive Tract. Respiratory System National Heart, Lung, and Blood Institute HealthTalk COPD (chronic obstructive pulmonary disease) American Lung Association - Disease Finder Association of Legal Aid Attorneys/UAW 2325 Canadian Lung Association Kids Health Family Living and Personal Living - Ms. Schultz added this link because on this page there is CDC, American ...

  7. Human Rights/Human Needs.

    ERIC Educational Resources Information Center

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  8. Methotrexate inhibits the first committed step of purine biosynthesis in mitogen-stimulated human T-lymphocytes: a metabolic basis for efficacy in rheumatoid arthritis?

    PubMed Central

    Fairbanks, L D; Rückemann, K; Qiu, Y; Hawrylowicz, C M; Richards, D F; Swaminathan, R; Kirschbaum, B; Simmonds, H A

    1999-01-01

    The immunosuppressive and anti-inflammatory effects of low-dose methotrexate (MTX) have been related directly to inhibition of folate-dependent enzymes by polyglutamated derivatives, or indirectly to adenosine release and/or apoptosis and clonal deletion of activated peripheral blood lymphocytes in S-phase. In this study of phytohaemagglutinin-stimulated primary human T-lymphocytes we show that MTX (20 nM to 20 microM) was cytostatic not cytotoxic, halting proliferation at G(1). This stasis of blastogenesis was associated with an inhibition of purine ribonucleotide synthesis but a stimulation of pyrimidine biosynthesis, the normal mitogen-induced expansion of ATP and GTP pools over 72 h being restricted to concentrations of unstimulated T-cells, whereas the increment in UTP pools exceeded that of controls. Decreased incorporation of H(14)CO(3) or [(14)C]glycine into purine ribonucleotides, with no radiolabel accumulation in any de novo synthetic intermediate but enhanced H(14)CO(3) incorporation into UTP, supported these MTX-related effects. Exaggerated [(14)C]hypoxanthine salvage (which normalized the purine and UTP pools) confirmed the increased availability of 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) as the molecular mechanism underlying these disparate changes. These results provide the first substantive evidence that the immunosuppressive effects of low-dose MTX in primary blasting human T-lymphocytes relate not to the inhibition of the two folate-dependent enzymes of purine biosynthesis but to inhibition of the first enzyme, amidophosphoribosyltransferase, thereby elevating PP-ribose-P and stimulating UTP synthesis. Varying cell types or incubation conditions employed by other workers, especially malignant/activated cells with high basal metabolic rates, might mask the effects noted in primary human T-lymphocytes. The findings imply the involvement of low-dose MTX in the inhibition of T-lymphocyte proliferation and proliferation-dependent processes in rheumatoid arthritis. PMID:10432311

  9. Interstellar humanity

    Microsoft Academic Search

    Steven J Dick

    2000-01-01

    Fifty years after Olaf Stapledon's landmark essay “Interplanetary man?”, we propose the coming era of “interstellar humanity”. Over the next 1000 years the domain of humanity will increasingly spread to the stars, a process that will alter our future in profound ways. At least three factors will drive this expansion: (1) increased understanding of cosmic evolution, changing our perception of

  10. Germ Line Variants of Human N-Methylpurine DNA Glycosylase Show Impaired DNA Repair Activity and Facilitate 1,N6-Ethenoadenine-induced Mutations.

    PubMed

    Adhikari, Sanjay; Chetram, Mahandranauth A; Woodrick, Jordan; Mitra, Partha S; Manthena, Praveen V; Khatkar, Pooja; Dakshanamurthy, Sivanesan; Dixon, Monica; Karmahapatra, Soumendra K; Nuthalapati, Nikhil K; Gupta, Suhani; Narasimhan, Ganga; Mazumder, Raja; Loffredo, Christopher A; Üren, Aykut; Roy, Rabindra

    2015-02-20

    Human N-methylpurine DNA glycosylase (hMPG) initiates base excision repair of a number of structurally diverse purine bases including 1,N(6)-ethenoadenine, hypoxanthine, and alkylation adducts in DNA. Genetic studies discovered at least eight validated non-synonymous single nucleotide polymorphisms (nsSNPs) of the hMPG gene in human populations that result in specific single amino acid substitutions. In this study, we tested the functional consequences of these nsSNPs of hMPG. Our results showed that two specific arginine residues, Arg-141 and Arg-120, are important for the activity of hMPG as the germ line variants R120C and R141Q had reduced enzymatic activity in vitro as well as in mammalian cells. Expression of these two variants in mammalian cells lacking endogenous MPG also showed an increase in mutations and sensitivity to an alkylating agent compared with the WT hMPG. Real time binding experiments by surface plasmon resonance spectroscopy suggested that these variants have substantial reduction in the equilibrium dissociation constant of binding (KD) of hMPG toward 1,N(6)-ethenoadenine-containing oligonucleotide (?A-DNA). Pre-steady-state kinetic studies showed that the substitutions at arginine residues affected the turnover of the enzyme significantly under multiple turnover condition. Surface plasmon resonance spectroscopy further showed that both variants had significantly decreased nonspecific (undamaged) DNA binding. Molecular modeling suggested that R141Q substitution may have resulted in a direct loss of the salt bridge between ?A-DNA and hMPG, whereas R120C substitution redistributed, at a distance, the interactions among residues in the catalytic pocket. Together our results suggest that individuals carrying R120C and R141Q MPG variants may be at risk for genomic instability and associated diseases as a consequence. PMID:25538240

  11. Water: Human Health

    MedlinePLUS

    ... Quality Standards Water Quality Criteria Human Health Criteria Human Health Criteria Human health ambient water quality criteria ... Updated National Recommended Water Quality Criteria - Human Health Human Health Research Program Human Health Research provides the ...

  12. Human Evolution

    NSDL National Science Digital Library

    Lee, Amy.

    2002-01-01

    The first Web site is an article from the New York Times (1) detailing some recent fossil discoveries that are shaking the paleontological world (free registration is required). Another relatively recent article from Guardian Unlimited (2) discusses a scientific debate surrounding the question of whether "a Western lifestyle now protects humanity from the forces that used to shape Homo sapiens." The third resource (3) includes a likely timeline of events in the history of hominids and a tour of the fossil record. A second timeline from the Huntarian Museum and Art Gallery at the University of Glasgow (4) is less detailed, but links to many major fossil discoveries of human and pre-human history. An "overview of the study of human evolution, and of the currently accepted fossil evidence" (5) is used to inform arguments for creationists and evolutionists. An interesting site from the University of California Santa Barbara (6) (last mentioned in the December 1, 1998 Scout Report for Social Sciences) presents 3-dimensional views of "modern primate relatives and fossil ancestors of humans." The interactive documentary from the Institute of Human Origins (7) (last mentioned in the April 20, 2001 Scout Report) is a great resource for those with the Flash plug-in and a high speed connection. Lastly, a resource from PBS.org (8) focuses on human evolution in a format aimed at kids.

  13. Human angiostrongyliasis.

    PubMed

    Wang, Qiao-Ping; Lai, De-Hua; Zhu, Xing-Quan; Chen, Xiao-Guang; Lun, Zhao-Rong

    2008-10-01

    Human angiostrongyliasis caused by Angiostrongylus cantonensis, a rat lungworm, has been reported globally. Human infections are acquired by ingestion of raw or undercooked snails or slugs, paratenic hosts such as prawns, or contaminated vegetables that contain the infective larvae of the worm. So far, at least 2827 cases of the disease have been documented worldwide. During the past few years, several outbreaks of human angiostrongyliasis have been reported in mainland China, Taiwan, and the USA. Additionally, sporadic cases in travellers who have returned from endemic areas have been reported. We review the clinical features, diagnosis, and treatment of human angiostrongyliasis, and describe the geographical distribution and prevalence of A cantonensis. Educating the public about the dangers of eating raw or undercooked intermediate and paratenic hosts in endemic areas is essential for the prevention and control of this foodborne zoonotic disease. PMID:18922484

  14. Human Evolution

    NSDL National Science Digital Library

    This resource from PBS focuses on human evolution in a format aimed at kids but easily adapted to a classroom of any kind. A classroom activity (available as Shockwave or text only formats) describes the steps in human evolution (physically and behaviorally) from Ardipithecus ramidus about 4.4 million years ago to our current state as modern Homo sapiens. There are also brief summaries of the importance of Lucy, fossilized footprints, and the "Taung child," the first Autralopithecus specimen found.

  15. Human monkeypox.

    PubMed

    McCollum, Andrea M; Damon, Inger K

    2014-01-01

    Human monkeypox is a zoonotic Orthopoxvirus with a presentation similar to smallpox. Clinical differentiation of the disease from smallpox and varicella is difficult. Laboratory diagnostics are principal components to identification and surveillance of disease, and new tests are needed for a more precise and rapid diagnosis. The majority of human infections occur in Central Africa, where surveillance in rural areas with poor infrastructure is difficult but can be accomplished with evidence-guided tools and educational materials to inform public health workers of important principles. Contemporary epidemiological studies are needed now that populations do not receive routine smallpox vaccination. New therapeutics and vaccines offer hope for the treatment and prevention of monkeypox; however, more research must be done before they are ready to be deployed in an endemic setting. There is a need for more research in the epidemiology, ecology, and biology of the virus in endemic areas to better understand and prevent human infections. PMID:24158414

  16. Human Anatomy

    NSDL National Science Digital Library

    The EMuseum at the University of Minnesota-Mankato provides this educational site on human anatomy. Although some parts of the site are still under construction, the Introduction to the Skeletal System section offers a straightforward introduction to the topic, complete with black-and-white skeletal photographs. Topics in this section include skeletal functions, axial and appendicular divisions, types of bone, bone composition, and a brief list of anatomical terms. For educators of introductory human anatomy, this site should provide interesting supplemental information.

  17. Behavior, human.

    PubMed

    Molteni, M

    2010-01-01

    Human behavior is the collection of actions or reactions exhibited by human beings in relation to the environment, and it can be categorized as either innate or learned. In psychology, behavior became an important construct with the advent of behaviorism, a theoretical framework that required the study of only observable facts or events which can be seen or manipulated, in response to external or internal stimuli. More recently, the Relational Frame Theory (RFT) suggests that also some psychological events such as thoughts and emotions can be explained as learned responses. In TACT project, behavior is the voluntary movement of reaching and grasping in a fixed condition. PMID:20393688

  18. Novel assay for simultaneous measurement of pyridine mononucleotides synthesizing activities allows dissection of the NAD(+) biosynthetic machinery in mammalian cells.

    PubMed

    Zamporlini, Federica; Ruggieri, Silverio; Mazzola, Francesca; Amici, Adolfo; Orsomando, Giuseppe; Raffaelli, Nadia

    2014-11-01

    The redox coenzyme NAD(+) is also a rate-limiting co-substrate for several enzymes that consume the molecule, thus rendering its continuous re-synthesis indispensable. NAD(+) biosynthesis has emerged as a therapeutic target due to the relevance of NAD(+) -consuming reactions in complex intracellular signaling networks whose alteration leads to many neurologic and metabolic disorders. Distinct metabolic routes, starting from various precursors, are known to support NAD(+) biosynthesis with tissue/cell-specific efficiencies, probably reflecting differential expression of the corresponding rate-limiting enzymes, i.e. nicotinamide phosphoribosyltransferase, quinolinate phosphoribosyltransferase, nicotinate phosphoribosyltransferase and nicotinamide riboside kinase. Understanding the contribution of these enzymes to NAD(+) levels depending on the tissue/cell type and metabolic status is necessary for the rational design of therapeutic strategies aimed at modulating NAD(+) availability. Here we report a simple, fast and sensitive coupled fluorometric assay that enables simultaneous determination of the four activities in whole-cell extracts and biological fluids. Its application to extracts from various mouse tissues, human cell lines and plasma yielded for the first time an overall picture of the tissue/cell-specific distribution of the activities of the various enzymes. The screening enabled us to gather novel findings, including (a) the presence of quinolinate phosphoribosyltransferase and nicotinamide riboside kinase in all examined tissues/cell lines, indicating that quinolinate and nicotinamide riboside are relevant NAD(+) precursors, and (b) the unexpected occurrence of nicotinate phosphoribosyltransferase in human plasma. PMID:25223558

  19. Human torso

    NSDL National Science Digital Library

    William Cheselden (None; )

    2000-04-02

    The torso is the central area of the body that all the other body parts connect to. The ribcage contains the lungs and the heart. The intestines are located below them. The pelvic region contains the human reproductive parts and parts of the digestive and waste tracts.

  20. Nothing Human

    ERIC Educational Resources Information Center

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  1. Human Impact

    NSDL National Science Digital Library

    Collection of nine classroom activities that focus on human impact on the environment. Topics include: oil spills; oil consumption; oil tanker size; greenhouse effect; salt water incursion; ozone hole and its affect on the food web; and zebra mussels. Each activity provides list of materials needed, background information, and procedure.

  2. Human Trafficking

    ERIC Educational Resources Information Center

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  3. Human Hibernation

    Microsoft Academic Search

    C. K. Bushe

    1885-01-01

    MY letter on the Hibernation of the Siberian mammoth has been followed by two others, extremely interesting, but dealing, I may say exclusively, with the question of human hibernation, and the evidence offered in support of it; this raises a very important consideration, concerning which I ask leave to offer a few remarks:-The ``fact,'' as stated by Mr. Braid, is

  4. Human schistosomiasis

    Microsoft Academic Search

    Bruno Gryseels; Katja Polman; Jan Clerinx; Luc Kestens

    2006-01-01

    Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta, specifi c freshwater snails as intermediate hosts, and human water contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum. According to WHO, 200 million people are infected worldwide, leading to the loss

  5. Human Herpesvirus 8 Open Reading Frame 21 Is a Thymidine and Thymidylate Kinase of Narrow Substrate Specificity That Efficiently Phosphorylates Zidovudine but Not Ganciclovir

    PubMed Central

    Gustafson, Erik A.; Schinazi, Raymond F.; Fingeroth, Joyce D.

    2000-01-01

    Human herpesvirus 8 (HHV8) open reading frame (ORF) 21 is predicted to encode a protein similar to the thymidine kinase (TK) enzyme of other herpesviruses. Expressed in mammalian cells, ORF 21 was found to have low TK activity, based on poor growth in media containing hypoxanthine-aminopterin-thymidine (HAT) and low incorporation of [3H]thymidine into high-molecular-weight DNA. Kinetic analysis using HHV8 TK as a purified glutathione S-transferase (GST) fusion protein showed that the enzyme has a comparatively high Km for thymidine (dThd) of ?33.2 ?M. Nearly 50% of the phosphorylated product of the reaction with dThd was thymidylate. This monophosphate kinase activity was more pronounced with 3?-azido-3?-deoxythymidine (AZT), in which 78% of the reaction product was AZT diphosphate. Thymidine analogs competitively inhibited dThd phosphorylation by HHV8 TK, while 2?-deoxyguanosine, 2?-deoxyadenosine, 2?-deoxycytidine, and corresponding analogs did not. Further competition experiments revealed that the nucleoside analog ganciclovir (GCV), at up to 1,000-fold molar excess, could not significantly inhibit dThd phosphorylation by the enzyme. In support of these data, 143B TK? cells expressing HHV8 TK phosphorylated GCV very poorly and were not susceptible to GCV toxicity compared to parental cells. Phosphorylation of [3H]GCV by a purified GST-HHV8 TK fusion protein was not detected by high-pressure liquid chromatography analysis. Structural features of HHV8 TK substrate recognition were investigated. Therapeutic implications of these findings are discussed. PMID:10623730

  6. Obesity-Related Metabolomic Analysis of Human Subjects in Black Soybean Peptide Intervention Study by Ultraperformance Liquid Chromatography and Quadrupole-Time-of-Flight Mass Spectrometry

    PubMed Central

    Kim, Min Jung; Yang, Hye Jeong; Kim, Jin Hee; Ahn, Chang-Won; Lee, Jong Ho; Kim, Kang Sung; Kwon, Dae Young

    2013-01-01

    The present study aimed to identify key metabolites related to weight reduction in humans by studying the metabolic profiles of sera obtained from 34 participants who underwent dietary intervention with black soybean peptides (BSP) for 12 weeks. This research is a sequel to our previous work in which the effects of BSP on BMI and blood composition of lipid were investigated. Sera of the study were subjected to ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and the data were analyzed using partial least-squares discriminate analysis (PLS-DA) score plots. Body mass index and percent body fat of the test group were reduced. Levels of betaine, benzoic acid, pyroglutamic acid, pipecolic acid, N-phenylacetamide, uric acid, l-aspartyl-l-phenylalanine, and lysophosphatidyl cholines (lysoPCs) (C18:1, C18:2, C20:1, and C20:4) showed significant increases. Levels of l-proline, valine, l-leucine/isoleucine, hypoxanthine, glutamine, l-methionine, phenylpyruvic acid, several carnitine derivatives, and lysoPCs (C14:0, PC16:0, C15:0, C16:0, C17:1, C18:0, and C22:0) were significantly decreased. In particular, lysoPC 16:0 with a VIP value of 12.02 is esteemed to be the most important metabolite for evaluating the differences between the 2 serum samples. Our result confirmed weight-lowering effects of BSP, accompanied by favorable changes in metabolites in the subjects' blood. Therefore, this research enables us to better understand obesity and increases the predictability of the obesity-related risk by studying metabolites present in the blood. PMID:23862058

  7. Comparison of transformation efficiency of human active and inactive X-chromosomal DNA

    Microsoft Academic Search

    Lee Venolia

    1983-01-01

    The mechanism of X-chromosome inactivation has been investigated recently using DNA-mediated transformation of the X-linked hypoxanthine phosphoribosyl transferase (hprt) locus. Several experiments indicate that inactive X-chromosomal DNA does not function in HPRT transformation. Liskay and Evans1 used DNA from hamster or mouse cells which had an hprt- allele on the active X chromosome and an hprt+ allele on the inactive

  8. In vitro growth inhibition of Plasmodium falciparum by retinol at concentrations present in normal human serum

    Microsoft Academic Search

    T. M. E. Davis; T. S. Skinner-Adams; J. Beilby

    1998-01-01

    To assess the in vitro effect of retinol on Plasmodium falciparum, the standard isolates 3D7, D10, W2 and K1 in continuous culture were exposed to retinol added in concentrations ranging from 10?7 to 0.1 ?mol\\/l. Parasite growth inhibition was assessed from 3H-hypoxanthine incorporation. Triplicate experiments were performed at physiological pH and in the case of D10, additional experiments were performed

  9. Human Ectoparasites

    NSDL National Science Digital Library

    Sohmer, Rachel.

    Don't let the bedbugs bite! Actually, if you were to worry about all of the parasites living on your body (sometimes helping you out), you'd never fall asleep in the first place. As a living organism part of a bigger ecosystem, humans play host to unumerable other living things. This Topic In Depth offers a look into the fascinating world of Human Ectoparasites.The first stop -- a page from encyclopedia-style Web site InnVista -- offers a brief introduction to some of the ectoparasitic species that make their living off the human body (1). The next two sites contain science news articles courtesy of the Australian Broadcasting Corporation. The first article relates how the evolution of human body lice was made possible when we developed the habit of wearing clothes some 40,000 years ago (2). The second describes an alternative hypothesis as to why humans lost their fur. The University of Sydney and Westmead Hospital, Australia offers a quick introduction to the bedbug in the following Web site (4), while the University of Kentucky entomology department does the same for chiggers in the next (5). Kansas State University offers a few pictures and interesting tidbits on tooth amoebas, the toothbrush-fleeing microscopic parasites found where the teeth meet the gums (6). Don't worry, tooth amoebas are generally good for you. Another example of a beneficial ectoparasite is the leech, which is making a comeback in medical circles for its anticoagulant properties and other medicinal uses as related in an article from the BBC News (7). And finally, Duke University offers a intriguing introduction to eyebrow mites, benign parasites that live in our eyebrow follicles and are thus somewhat limited in their choice of mates (8).

  10. Human Capital, (Human) Capabilities and Higher Education

    ERIC Educational Resources Information Center

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  11. Introduction Human Development/Human Devel-

    E-print Network

    Banbara, Mutsunori

    20 Introduction Guide Entrance Life Career Inquiries Human Development/Human Devel- opment a sustainable society that allows us to maintain our humanity. Japan faces pressing issues such as rapid issues, the GraduateSchoolofHumanDevelopmentandEnvironment and the Faculty of Human Development

  12. Human Rights

    NSDL National Science Digital Library

    The idea of "human rights" is a relatively new development in history, but as this website from Britain's National Archives notes in its discussion of the long trajectory of struggles for equality and so forth, "We could do worse than characterizing this history as the struggle for human rights." This visually compelling online exhibit uses original documents from The National Archives to take a long view of these struggles and movements. Visitors can start their journey through the site by picking a time period, and then reading an introductory essay on the period. Each time period includes a timeline and links to digitized version of relevant documents, such as The Poor Act of 1601 and a poster for a Staffordshire coal miners' union public meeting from 1831. The site is rounded out by a thorough glossary and a document index.

  13. Human Anatomy

    NSDL National Science Digital Library

    This website, crafted by the State University of New York-Upstate Medical University, brings together key resources for students and others interested in human anatomy. These materials were designed with first year medical students in mind, but they will also be of use to individuals taking biology and other science-related courses. On the site, visitors can make their way through six sections ranging from extremities to the head and neck. Each area contains a variety of detailed anatomical charts, glossaries, and images. Radiology resources are also prominently featured within each section, providing students with a different perspective of the human body through x-rays, CT scans, and MRIs. Other helpful resources include fact sheets, quizzes, teaching materials, and other freely available course materials offered from other medical schools.

  14. Human Locomotion

    PubMed Central

    Inman, Verne T.

    1966-01-01

    The development of bipedal plantigrade progression is a purely human, and apparently learned, accomplishment. Experimental findings confirm the hypothesis that the human body will integrate the motion of various segments of the body and control the activity of muscles to minimize energy expenditure. Movements which are integrated for this purpose include vertical displacement of the body, horizontal rotation of the pelvis, mediolateral pelvic tilt, flexion of the knee, plantar flexion of the ankle and foot, lateral displacement of the torso and rotation of the shoulder girdle. Raising and lowering the body results in gains and losses of potential energy, and acceleration and deceleration result in gains and losses of kinetic energy. The motions are so co-ordinated that a transfer of energy back and forth from kinetic to potential occurs during walking, which tends to minimize total energy expenditure as well as muscle work. ImagesFig. 1 PMID:5942660

  15. Human Chromosomes

    NSDL National Science Digital Library

    BEGIN:VCARD VERSION:2.1 FN:Access Excellence N:Excellence; Access REV:2005-03-12 END:VCARD

    2005-03-12

    Representation of the 23 paired chromosomes of the human male. Chromosome: a very long DNA molecule and associated proteins, that carry portions of the hereditary information of an organism. a. Structure of a chromosome (Typical metaphase chromosome): A chromosome is formed from a single DNA molecule that contains many genes. A chromosomal DNA molecule contains three specific nucleotide sequences which are required for replication: a DNA replication origin; a centromere to attach the DNA to the mitotic spindle.; a telomere located at each end of the linear chromosome. The DNA molecule is highly condensed. The human DNA helix occupy too much space in the cell. Small proteins are responsible for packing the DNA into units called nucleosomes. b. Stained chromosomes: Chromosomes are stained with A-T (G bands) and G-C (R bands) base pair specific dyes. When they are stained, the mitotic chromosomes have a banded structure that unambiguously identifies each chromosome of a karyotype. Each band contains millions of DNA nucleotide pairs which do not correspond to any functional structure. Adapted from K.F. Jorgenson, J.H. van de Sande, and C.C. Lin, Chromosoma 68:287-302, 1978. c. Karyotype of a male: The human haploid genome contains 3,000,000,000 DNA nucleotide pairs, divided among twenty two (22) pairs of autosomes and one pair of sex chromosomes.

  16. Lateralized effect of pallidal stimulation on self-mutilation in Lesch-Nyhan disease.

    PubMed

    Abel, Taylor J; Dalm, Brian D; Grossbach, Andrew J; Jackson, Adam W; Thomsen, Teri; Greenlee, Jeremy D W

    2014-12-01

    Lesch-Nyhan disease (LND) is an X-linked hereditary disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase. This syndrome is characterized by hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia. The authors describe the case of a 15-year-old boy who underwent bilateral placement of globus pallidus internus (GPi) deep brain stimulation (DBS) electrodes for the treatment of generalized dystonia. His self-mutilating behavior gradually disappeared several weeks after the start of GPi stimulation. The dystonia and self-mutilating behavior returned on the left side only after a right lead fracture. This case is the first reported instance of LND treated with DBS in which the stimulation was interrupted and the self-mutilation returned in a lateralized fashion. The findings indicate that the neurobehavioral aspect of LND is lateralized and that contralateral GPi stimulation is responsible for lateralized improvement in self-injurious behavior. PMID:25303157

  17. From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics.

    PubMed

    Trigueros Genao, M; Torres, R J

    2014-11-01

    Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease. PMID:24863549

  18. Human Metapnemovirus (HMPV)

    MedlinePLUS

    ... Register for ENews Home > Lung Disease > Human Metapneumovirus Human Metapneumovirus Human metapneumovirus (hMPV) is a recently identified member of ... respiratory illnesses for at least 50 years worldwide. Human metapneumovirus can cause upper and lower respiratory tract ...

  19. Human Propulsion

    NSDL National Science Digital Library

    John Pratte

    This lesson points out that the motion of objects (velocity or acceleration) is almost never constant, and applies this idea to the motion of a person walking. The discussion covers the energy transfers involved in walking and in some other forms of human-powered transportation (crutches, bicycle, wheelchair), and the velocity and acceleration of an object that is moving in one dimension. The lesson includes an activity in which students use an accelerometer attached to a student volunteer to measure instantaneous acceleration in three dimensions, and calculate the total work which is done.

  20. Human schistosomiasis.

    PubMed

    Colley, Daniel G; Bustinduy, Amaya L; Secor, W Evan; King, Charles H

    2014-06-28

    Human schistosomiasis--or bilharzia--is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. PMID:24698483

  1. Teaching Human Rights: Evaluating Human Rights Education

    Microsoft Academic Search

    Anja Mihr

    Human rights education (HRE) is currently discussed as one of the key means to establish sustainable and long-term stable societies. HRE contributes to the dissemination of the Universal Declaration of Human Rights (UDHR) from 1948 and to help creating a culture of Human Rights. There are dozens of international legal human rights frameworks such as conventions and treaties of the

  2. Human Subjects Section 6. Protection of Human

    E-print Network

    Heller, Barbara

    Human Subjects Section 6. Protection of Human Subjects This section is required for applicants answering "yes" to the question "Are human subjects involved?" on the R&R Other Project Information form. If the answer is "No" to the question but the proposed research involves human specimens and/or data from

  3. Human cooperation.

    PubMed

    Rand, David G; Nowak, Martin A

    2013-08-01

    Why should you help a competitor? Why should you contribute to the public good if free riders reap the benefits of your generosity? Cooperation in a competitive world is a conundrum. Natural selection opposes the evolution of cooperation unless specific mechanisms are at work. Five such mechanisms have been proposed: direct reciprocity, indirect reciprocity, spatial selection, multilevel selection, and kin selection. Here we discuss empirical evidence from laboratory experiments and field studies of human interactions for each mechanism. We also consider cooperation in one-shot, anonymous interactions for which no mechanisms are apparent. We argue that this behavior reflects the overgeneralization of cooperative strategies learned in the context of direct and indirect reciprocity: we show that automatic, intuitive responses favor cooperative strategies that reciprocate. PMID:23856025

  4. Queuine, a tRNA anticodon wobble base, maintains the proliferative and pluripotent potential of HL-60 cells in the presence of the differentiating agent 6-thioguanine.

    PubMed Central

    French, B T; Patrick, D E; Grever, M R; Trewyn, R W

    1991-01-01

    6-Thioguanine (6-TG)-induced differentiation of hypoxanthine phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8)-deficient HL-60 cells is characterized by 2 days of growth, after which morphological differentiation proceeds. Addition of the tRNA wobble base queuine, in the presence of 6-TG, maintains the proliferative capability of the cells. The ability of 6-TG to induce differentiation correlates with c-myc mRNA down-regulation, but queuine has no effect on this parameter. Treatment with 6-TG for 2-3 days commits HL-60 cells to granulocytic differentiation, and, once committed, these cells do not respond to the monocytic inducer phorbol 12-myristate 13-acetate. Nonetheless, when cells are treated with queuine and 6-TG, they maintain the promyelocytic morphology and are capable of being induced down the monocytic pathway by phorbol 12-myristate 13-acetate as indicated by stabilization of c-fms mRNA and cell adherence. In the absence of queuine, phorbol 12-myristate 13-acetate is incapable of inducing monocytic markers in the 6-TG-treated cells. The data presented indicate that 6-TG-induced differentiation of HL-60 cells is a tRNA-facilitated event and that the tRNA wobble base queuine is capable of maintaining both the proliferative and pluripotent potential of the cells. Images PMID:1988936

  5. Purine Salvage in Two Halophilic Archaea: Characterization of Salvage Pathways and Isolation of Mutants Resistant to Purine Analogs

    PubMed Central

    Stuer-Lauridsen, Birgitte; Nygaard, Per

    1998-01-01

    In exponentially growing cultures of the extreme halophile Halobacterium halobium and the moderate halophile Haloferax volcanii, growth characteristics including intracellular protein levels, RNA content, and nucleotide pool sizes were analyzed. This is the first report on pool sizes of nucleoside triphosphates, NAD, and PRPP (5-phosphoribosyl-?-1-pyrophosphate) in archaea. The presence of a number of salvage and interconversion enzymes was determined by enzymatic assays. The levels varied significantly between the two organisms. The most significant difference was the absence of GMP reductase activity in H. halobium. The metabolism of exogenous purines was investigated in growing cultures. Both purine bases and nucleosides were readily taken up and were incorporated into nucleic acids. Growth of both organisms was affected by a number of inhibitors of nucleotide synthesis. H. volcanii was more sensitive than H. halobium, and purine base analogs were more toxic than nucleoside analogs. Growth of H. volcanii was inhibited by trimethoprim and sulfathiazole, while these compounds had no effect on the growth of H. halobium. Spontaneous mutants resistant to purine analogs were isolated. The most frequent cause of resistance was a defect in purine phosphoribosyltransferase activity coupled with reduced purine uptake. A single phosphoribosyltransferase seemed to convert guanine as well as hypoxanthine to nucleoside monophosphates, and another phosphoribosyltransferase had specificity towards adenine. The differences in the metabolism of purine bases and nucleosides and the sensitivity to purine analogs between the two halobacteria were reflected in differences in purine enzyme levels. Based on our results, we conclude that purine salvage and interconversion pathways differ just as much between the two archaeal species as among archaea, bacteria, and eukarya. PMID:9457844

  6. Human Factors in Human-Systems Integration

    NASA Technical Reports Server (NTRS)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  7. integration division Human Systems

    E-print Network

    integration division Human Systems Exploration of Human Systems Integration Issues in Next to understand potential human performance and human- system interactions issues related to NextGen concepts together as a single system. We accomplish this by exploring human-system interaction issues in a high

  8. Human Rhinoviruses

    PubMed Central

    Lamson, Daryl M.; St. George, Kirsten; Walsh, Thomas J.

    2013-01-01

    Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs. PMID:23297263

  9. Human oestrus

    PubMed Central

    Gangestad, Steven W; Thornhill, Randy

    2008-01-01

    For several decades, scholars of human sexuality have almost uniformly assumed that women evolutionarily lost oestrus—a phase of female sexuality occurring near ovulation and distinct from other phases of the ovarian cycle in terms of female sexual motivations and attractivity. In fact, we argue, this long-standing assumption is wrong. We review evidence that women's fertile-phase sexuality differs in a variety of ways from their sexuality during infertile phases of their cycles. In particular, when fertile in their cycles, women are particularly sexually attracted to a variety of features that likely are (or, ancestrally, were) indicators of genetic quality. As women's fertile-phase sexuality shares with other vertebrate females' fertile-phase sexuality a variety of functional and physiological features, we propose that the term oestrus appropriately applies to this phase in women. We discuss the function of women's non-fertile or extended sexuality and, based on empirical findings, suggest ways that fertile-phase sexuality in women has been shaped to partly function in the context of extra-pair mating. Men are particularly attracted to some features of fertile-phase women, but probably based on by-products of physiological changes males have been selected to detect, not because women signal their cycle-based fertility status. PMID:18252670

  10. Visible Human Project

    MedlinePLUS

    ... Tools Media Productions Related Projects The Visible Human Project ® Overview The Visible Human Project ® is an outgrowth of the NLM's 1986 Long- ... The long-term goal of the Visible Human Project ® is to produce a system of knowledge structures ...

  11. Measurement of Human Intelligence

    E-print Network

    Ranjith Engu; Sairam Vakkalanka; Blekinge Tekniska Högskola

    Abstract ––This paper describes about the need for measuring the human intelligence, definitions and sub attributes of intelligence, different measures and measuring scales of human intelligence. Keywords––Measurement, Intelligence, human intelligence, scales of measurement. I.

  12. Human-machine interactions

    DOEpatents

    Forsythe, J. Chris (Sandia Park, NM); Xavier, Patrick G. (Albuquerque, NM); Abbott, Robert G. (Albuquerque, NM); Brannon, Nathan G. (Albuquerque, NM); Bernard, Michael L. (Tijeras, NM); Speed, Ann E. (Albuquerque, NM)

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  13. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. (Mount Sinai Hospital, Toronto, Ontario (Canada). Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  14. Human Research Protection Program Plan

    E-print Network

    Weber, David J.

    Human Research Protection Program Plan Revised February 27, 2014 #12;Human Research Protection............................................................................................................... 4 Engaged in Human Research...................................................................................... 4 Human Research

  15. Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: insights into mechanisms of familial Parkinson's disease.

    PubMed

    Triplett, Judy C; Zhang, Zhaoshu; Sultana, Rukhsana; Cai, Jian; Klein, Jon B; Büeler, Hansruedi; Butterfield, David Allan

    2015-06-01

    Parkinson's disease (PD) is an age-related, neurodegenerative motor disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and presence of ?-synuclein-containing protein aggregates. Mutations in the mitochondrial Ser/Thr kinase PTEN-induced kinase 1 (PINK1) are associated with an autosomal recessive familial form of early-onset PD. Recent studies have suggested that PINK1 plays important neuroprotective roles against mitochondrial dysfunction by phosphorylating and recruiting Parkin, a cytosolic E3 ubiquitin ligase, to facilitate elimination of damaged mitochondria via autophagy-lysosomal pathways. Loss of PINK1 in cells and animals leads to various mitochondrial impairments and oxidative stress, culminating in dopaminergic neuronal death in humans. Using a 2-D polyacrylamide gel electrophoresis proteomics approach, the differences in expressed brain proteome and phosphoproteome between 6-month-old PINK1-deficient mice and wild-type mice were identified. The observed changes in the brain proteome and phosphoproteome of mice lacking PINK1 suggest that defects in signaling networks, energy metabolism, cellular proteostasis, and neuronal structure and plasticity are involved in the pathogenesis of familial PD. Mutations in PINK1 are associated with an early-onset form of Parkinson's disease (PD). This study examines changes in the proteome and phosphoproteome of the PINK1 knockout mouse brain. Alterations were noted in several key proteins associated with: increased oxidative stress, aberrant cellular signaling, altered neuronal structure, decreased synaptic plasticity, reduced neurotransmission, diminished proteostasis networks, and altered metabolism. 14-3-3?, 14-3-3 protein epsilon; 3-PGDH, phosphoglycerate dehydrogenase; ALDOA, aldolase A; APT1, acyl-protein thioesterase 1; CaM, calmodulin; CBR3, carbonyl reductase [NADPH] 3; ENO2, gamma-enolase; HPRT, hypoxanthine-guanine phosphoribosyltransferase; HSP70, heat-shock-related 70 kDa protein 2; IDHc, cytoplasmic isocitrate dehydrogenase [NADP+]; MAPK1, mitogen-activated protein kinase 1; MEK1, MAP kinase kinase 1; MDHc, cytoplasmic malate dehydrogenase; NFM, neurofilament medium polypeptide; NSF, N-ethylmaleimide-sensitive fusion protein; PHB, prohibitin; PINK1, PTEN-induced putative kinase 1; PPIaseA, peptidyl-prolyl cis-trans isomerase A; PSA2, proteasome subunit alpha type-2; TK, transketolase; VDAC-2, voltage-dependent anion-selective channel protein 2. PMID:25626353

  16. Biological effectiveness of nuclear fragments produced by high-energy protons interacting in tissues near the bone- soft tissue interface

    NASA Astrophysics Data System (ADS)

    Shavers, Mark Randall

    1999-12-01

    High-energy protons in the galactic cosmic rays (GCR)-or generated by nuclear interactions of GCR heavy-ions with material-are capable of penetrating great thicknesses of shielding to irradiate humans in spacecraft or in lunar or Martian habitats. As protons interact with the nuclei of the elemental constituents of soft tissue and bone, low energy nuclei-target fragments-are emitted into the cells responsible for bone development and maintenance and for hematopoiesis. Leukemogenesis is the principal endpoint of concern because it is the most likely deleterious effect, and it has a short latency period and comparatively low survival rate, although other myelo- proliferative disorders and osteosarcoma also may be induced. A one-dimensional proton-target fragment transport model was used to calculate the energy spectra of fragments produced in bone and soft tissue, and present in marrow cavities at distances from a bone interface. In terms of dose equivalent, the target fragments are as significant as the incident protons. An average radiation quality factor was found to be between 1.8 and 2.6. Biological response to the highly non- uniform energy deposition of the target fragments is such that an alternative approach to conventional predictive risk assessment is needed. Alternative procedures are presented. In vitro cell response and relative biological effectiveness were calculated from the radial dose distribution of each fragment produced by 1-GeV protons using parameters of a modified Ion-Gamma- Kill (IGK) model of radiation action. The modelled endpoints were survival of C3H10t 1/2 and V79 cells, neoplastic transformation of C3H10t1/2 cells, and mutation of the X-linked hypoxanthine phosphoribosyltransferase (HPRT) locus in V79 cells. The dose equivalent and cell responses increased by 10% or less near the interface. Since RBE increases with decreasing dose in the IGK model, comparisons with quality factors were made at dose levels 0.01 <= D [Gy] <= 2. Applying average quality factors derived herein to GCR exposures results in a <= 5% increase of in average quality. Calculated RBEs indicate that accepted quality factors for high-energy protons may be too low due to the relatively high effectiveness of the low-charged target fragments. Derived RBEs for target fragments increase the calculated biological effectiveness of GCR by 20% to 180%.

  17. Adenosine kinase deficiency in tritiated deoxyadenosine-resistant mouse S49 lymphoma cell lines

    SciTech Connect

    Sastry, K.J.; Huang, C.; Chan, T.S.

    1987-12-01

    Mutant sublines were derived of S49 mouse T-lymphoma cells that were resistant to tritiated deoxyadenosine. Twenty-five isolates that were selected in 1 microCi/ml of the nucleoside were cross-resistant to 6-thioguanine, were sensitive to HAT (hypoxanthine, aminopterin, and thymidine), and contained less than 1% of hypoxanthine phosphoribosyltransferase activity in wild-type cells. One of the mutant clones, S49-dA2, was further subjected to selection in a medium containing 2 microCi/ml tritiated deoxyadenosine and 1 microgram/ml deoxycoformycin, an inhibitor of adenosine deaminase. All resistant subclones were cross-resistant to tubercidin, 6-methylmercaptopurine riboside, and arabinosyladenine. One of the subclones, S49-12, was completely devoid of adenosine kinase and was partially deficient in deoxyadenosine kinase. This subclone, however, contained wild-type levels of deoxycytidine kinase. DEAE chromatography of the wild-type cell extracts revealed two deoxyadenosine phosphorylating activities, one of which coeluted with adenosine kinase and was the enzyme missing in S49-12. The other species phosphorylated both deoxyadenosine and deoxycytidine, of which deoxycytidine was the preferred substrate.

  18. Purine metabolism in Toxoplasma gondii

    SciTech Connect

    Krug, E.C.; Marr, J.J.; Berens, R.L.

    1989-06-25

    We have studied the incorporation and interconversion of purines into nucleotides by freshly isolated Toxoplasma gondii. They did not synthesize nucleotides from formate, glycine, or serine. The purine bases hypoxanthine, xanthine, guanine, and adenine were incorporated at 9.2, 6.2, 5.1, and 4.3 pmol/10(7) cells/h, respectively. The purine nucleosides adenosine, inosine, guanosine, and xanthosine were incorporated at 110, 9.0, 2.7, and 0.3 pmol/10(7) cells/h, respectively. Guanine, xanthine, and their respective nucleosides labeled only guanine nucleotides. Inosine, hypoxanthine, and adenine labeled both adenine and guanine nucleotide pools at nearly equal ratios. Adenosine kinase was greater than 10-fold more active than the next most active enzyme in vitro. This is consistent with the metabolic data in vivo. No other nucleoside kinase or phosphotransferase activities were found. Phosphorylase activities were detected for guanosine and inosine; no other cleavage activities were detected. Deaminases were found for adenine and guanine. Phosphoribosyltransferase activities were detected for all four purine nucleobases. Interconversion occurs only in the direction of adenine to guanine nucleotides.

  19. Mutagenic activity of high-energy 532 nm ultra-short laser pulses.

    PubMed

    Leavitt, J; Fatone, M; Hestdalen, C; Obringer, J W; Tillinghast, H S

    1997-04-01

    The mutagenic activity of green (532 nm) and infrared (1064 nm) ultra-short laser light pulses was tested in cultured Syrian hamster fibroblasts by a hypoxanthine phosphoribosyl-transferase (HPRT) mutagenesis assay. In 18 irradiation trials, cells were exposed to eight consecutive 100-ps pulses of either 532 nm or 1064 nm light from a Nd:YAG laser at average irradiances of 3.0 GW/cm2. The 532 nm irradiations produced Hprt mutations at an average observed frequency of 5.3-5.6 x 10(-6), 10-fold higher than control trials (P < 0.01), while 1064 nm irradiations produced only background (spontaneous mutation) frequencies. A HAT (hypoxanthine, aminopterin, thymidine) sensitivity test allowed us to infer that Hprt- clones, selected as 6-thioguanine-resistant clones, possessed mutations at the Hprt locus after 532 nm Nd:YAG laser irradiation. The mutagenic effects of 532 nm high-energy laser pulses and not 1064 nm wavelengths are discussed in light of a two-photon absorption hypothesis. These preliminary findings suggest that 460-590 nm visible-light lasers may be mutagenic to mammalian cells either as a result of two-photon absorption or through some other photochemical process that damages DNA. PMID:9092930

  20. dGTP Starvation in Escherichia coli Provides New Insights into the Thymineless-Death Phenomenon

    PubMed Central

    Itsko, Mark; Schaaper, Roel M.

    2014-01-01

    Starvation of cells for the DNA building block dTTP is strikingly lethal (thymineless death, TLD), and this effect is observed in all organisms. The phenomenon, discovered some 60 years ago, is widely used to kill cells in anticancer therapies, but many questions regarding the precise underlying mechanisms have remained. Here, we show for the first time that starvation for the DNA precursor dGTP can kill E. coli cells in a manner sharing many features with TLD. dGTP starvation is accomplished by combining up-regulation of a cellular dGTPase with a deficiency of the guanine salvage enzyme guanine-(hypoxanthine)-phosphoribosyltransferase. These cells, when grown in medium without an exogenous purine source like hypoxanthine or adenine, display a specific collapse of the dGTP pool, slow-down of chromosomal replication, the generation of multi-branched nucleoids, induction of the SOS system, and cell death. We conclude that starvation for a single DNA building block is sufficient to bring about cell death. PMID:24810600

  1. Mutagenic activity of some clastogenic chemicals at the hypoxanthine guanine phosphoribosyl transferase locus of Chinese hamster ovary cells.

    PubMed

    Amacher, D E; Zelljadt, I

    1984-05-01

    4 presumptive clastogens (caffeine, dimethyl sulfoxide, diethylstilbestrol and p,p'-DDE) and 4 chemicals thought to induce chromosomal mutations in L5178Y mouse lymphoma cells (procarbazine X HCl, epichlorohydrin, hycanthone and iodomethane) were tested in the CHO/HGPRT gene mutation assay for the induction of 6-thioguanine-resistant ( 6TGR ) mutants. Of the clastogens, p,p'-DDE was mutagenic at several concentrations and diethylstilbestrol (DES) increased the 6TGR mutant frequency over control levels at the 6.7 and 8.0 micrograms/ml doses, but the results for DES were neither convincing nor significant. Caffeine was not mutagenic although at very high concentrations (6667-8000 micrograms/ml) there was a slight elevation in mutant frequency over background. This was probably due to a selective effect of caffeine against the HGPRT+ phenotype, for 2 different HGPRT- cell lines were refractory to the toxic effects of caffeine at the highest test level (8000 micrograms/ml). All 4 'chromosomal mutagens' produced dose-related increases in mutant frequencies at the HGPRT locus of these CHO cells. 6TGR colonies were generally uniform in size when normal precautions were taken to prevent the formation of satellite (secondary) colonies. Excepting DES, dimethyl sulfoxide, and caffeine, these data demonstrate that 5 of 8 clastogenic chemicals reproducibly induce mutations at the HGPRT locus of CHO cells which lack the small colony-forming potential of 3.7.2C L5178Y cells. PMID:6717480

  2. The Three-Dimensional Structures of Nicotinate Mononucleotide:5,6-Dimethylbenzimidazole Phosphoribosyltransferase (CobT) from

    E-print Network

    Rayment, Ivan

    and the small domain of the neighboring subunit. DMB binds in a hydrophobic pocket created in part of orga- nisms show that bacteria devote a significant amount of their genomic material to the synthesis

  3. Visualizing Humans by Computer.

    ERIC Educational Resources Information Center

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  4. Human Research Program Opportunities

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.

    2014-01-01

    The goal of HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Human Research Program was designed to meet the needs of human space exploration, and understand and reduce the risk to crew health and performance in exploration missions.

  5. Cognitive Science (Humanities)

    E-print Network

    Schnaufer, Achim

    Cognitive Science (Humanities) The University of Edinburgh College of Humanities and Social Science: Cognitive Science (Humanities) BSc Honours in: Cognitive Science Please see separate information sheets the disciplines that contribute to the study of human cognition. The Cognitive Science programme at Edinburgh

  6. Mapping Our Human Footprint

    NSDL National Science Digital Library

    "Human footprint" is a phrase used to describe the environmental impact humans have had on the Earth's surface. Students will use the Human Footprint interactive data map to analyze the degree of human impact in their hometown and make connections between areas of human impact and geographic factors. They will also have access to the Population Density layer map displaying areas that have been affected by human populations. Students can compare the two data layers on the interactive map and identify the differences they see.

  7. ROBERT PARK'S HUMAN ECOLOGY AND HUMAN GEOGRPHY

    Microsoft Academic Search

    J. NICHOLAS ENTRIKIN

    1980-01-01

    In describing the position of human ecology within the system of sciences, Robert Park was concerned with establishing the logical independence of ecology from geography. He used arguments of neo-Kantian philosophy, and to a lesser exten Comtean positivism, to accomplish his goal. The study of the philosophical context of Park's arguments on human science suggests that his views were more

  8. Boundaries of Humanities: Writing Medical Humanities

    ERIC Educational Resources Information Center

    Bolton, Gillie

    2008-01-01

    Literature and medicine is a discipline within medical humanities, which challenges medicine to reconfigure its scientific model to become interdisciplinary, and be disciplined by arts and humanities as well as science. The psychological, emotional, spiritual and physical are inextricably linked in people, inevitably entailing provisionality,…

  9. Designing human friendly human interaction proofs (HIPs)

    Microsoft Academic Search

    Kumar Chellapilla; Kevin Larson; Patrice Y. Simard; Mary Czerwinski

    2005-01-01

    HIPs, or Human Interactive Proofs, are challenges meant to be easily solved by humans, while remaining too hard to be economically solved by computers. HIPs are increasingly used to protect services against automatic script attacks. To be effective, a HIP must be difficult enough to discourage script attacks by raising the computation and\\/or development cost of breaking the HIP to

  10. Boundaries of Humanities: Writing Medical Humanities

    Microsoft Academic Search

    Gillie Bolton

    2008-01-01

    Literature and medicine is a discipline within medical humanities, which challenges medicine to reconfigure its scientific model to become interdisciplinary, and be disciplined by arts and humanities as well as science. The psychological, emotional, spiritual and physical are inextricably linked in people, inevitably entailing provisionality, disturbance and lack of certainty, and lack of closure and therefore of control. Arts and

  11. Climate and Human Evolution

    NSDL National Science Digital Library

    2010-09-22

    In this video segment adapted from NOVA: Becoming Human, learn how the analysis of rock layers and ocean sediments supports the theory that rapid climate change may have jump-started human evolution two million years ago.

  12. Human Resource Accounting System

    ERIC Educational Resources Information Center

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  13. Statement on Human Cloning

    MedlinePLUS

    ... Association for the Advancement of Science Statement on Human Cloning Tweet Email Print The American Association for the ... debates within our society on the issue of human cloning. Since 1997, AAAS has engaged the public and ...

  14. The Growing Human Population.

    ERIC Educational Resources Information Center

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  15. Pathfinder: Humans in space

    NASA Technical Reports Server (NTRS)

    Anderson, John L.

    1988-01-01

    Viewgraphs are presented on the Pathfinder program. Information is given on human exploration of the solar system, technical requirements interfaces, program objectives, space suits, human performance, man-machine systems, space habitats, life support systems, and artificial gravity

  16. Human bites (image)

    MedlinePLUS

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  17. Human Papillomavirus (HPV) Screening

    MedlinePLUS

    ... Search The CDC Cancel Submit Search The CDC Human Papillomavirus (HPV) Note: Javascript is disabled or is ... HPV Screening Recommend on Facebook Tweet Share Compartir Human papillomavirus (HPV) causes genital warts and cancers, such ...

  18. Human Specimen Resources | Resources

    Cancer.gov

    Researchers who utilize or require human specimens for their research may benefit from the information in this section, including how to find specimens for research, how to establish a tissue bank or resource, and funding opportunities related to human specimens.

  19. Patenting Human Evolution

    E-print Network

    Torrance, Andrew W.

    2008-06-01

    to thorough analysis and debate prior to the imminent arrival of human genetic enhancement technologies. Otherwise, patent law may drive human evolution in directions either unplanned - or worse - undesired....

  20. Telling the Human Story.

    ERIC Educational Resources Information Center

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  1. Programming with human computation

    E-print Network

    Little, Greg (Danny Greg)

    2011-01-01

    Amazon's Mechanical Turk provides a programmatically accessible micro-task market, allowing a program to hire human workers. This has opened the door to a rich field of research in human computation where programs orchestrate ...

  2. Understanding the Human Genome

    Microsoft Academic Search

    Douglas L. Brutlag

    1994-01-01

    Introduction to Molecular Medicine (pp. 153168). New York NY: Scientific American Inc.Understanding the Human GenomeDouglas L. Brutlag, Ph.D.There are many compelling reasons to determine the complete genetic information of thehuman organism. The genome contains the history of human evolution and specifies themechanism of human development; all humanity's physical capabilities and deficienciesare encoded in the genome. It is no wonder that

  3. The Human Body

    NSDL National Science Digital Library

    Miss Bratkiewicz

    2011-12-10

    We will be learning about The Human Body! Think about these questions as you go through: How does the muscular system work? Why is the skeletal system important? Hello 4A! Our next unit is learning about The Human Body! I want you to explore and come up with a burning question you have about The Human Body! Here is a fun fact about The Human Body: A baby has 300 bones at birth. An adult has ...

  4. HUMAN EXPOSURE ACTIVITY PATTERNS

    EPA Science Inventory

    Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

  5. Production Of Human Antibodies

    NASA Technical Reports Server (NTRS)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  6. The Virtual Physiological Human

    PubMed Central

    Coveney, Peter V.; Diaz, Vanessa; Hunter, Peter; Kohl, Peter; Viceconti, Marco

    2011-01-01

    The Virtual Physiological Human is synonymous with a programme in computational biomedicine that aims to develop a framework of methods and technologies to investigate the human body as a whole. It is predicated on the transformational character of information technology, brought to bear on that most crucial of human concerns, our own health and well-being.

  7. Financing Human Capital.

    ERIC Educational Resources Information Center

    Juffras, Jason; Sawhill, Isabel V.

    This paper examines the government's role in financing human capital investments. It first examines why private investments in education, training, and other forms of human capital are likely to fall short of socially desirable levels. It then reviews past trends in public support for human resource investments. Finally, it discusses current…

  8. Demystifying the Humanities.

    ERIC Educational Resources Information Center

    Bonham, George

    1980-01-01

    The new Rockefeller Foundation's Commission on the Humanities' report is discussed. Some of the commission's recommendations include: improved quality of elementary and secondary schools, strengthening of humanities research, reaffirmation within education of the values of the humanities, and closer collaboration of educational and cultural…

  9. A Human Rights Glossary.

    ERIC Educational Resources Information Center

    Flowers, Nancy

    1998-01-01

    Presents a human rights glossary that includes definitions of basic terms, treaties, charters, and groups/organizations that have been featured in previous articles in this edition of "Update on Law-Related Education"; the human rights terms have been compiled as part of the celebration of the Universal Declaration of Human Rights (UDHR). (CMK)

  10. THE 'HUMAN RIGHTS APPROACH'

    Microsoft Academic Search

    Ernst-Ulrich Petersmann

    2004-01-01

    The today universal recognition of 'inalienable' human rights implies that the legitimacy and legality of all government measures, including rules and decisions of intergovernmental organizations, depend also on their respect for human rights as defined in national constitutions and international law. This contribution argues that the universal human rights obligations of every Member of the World Trade Organization (WTO) pursue

  11. POTENTIALITY AND HUMAN EMBRYOS

    Microsoft Academic Search

    JOHN P. LIZZA

    2007-01-01

    ABSTRACTConsideration of the potentiality of human embryos to develop characteristics of personhood, such as intellect and will, has figured prominently in arguments against abortion and the use of human embryos for research. In particular, such consideration was the basis for the call of the US President's Council on Bioethics for a moratorium on stem cell research on human embryos. In

  12. The Humanities' Value

    ERIC Educational Resources Information Center

    Harpham, Geoffrey Galt

    2009-01-01

    Why should society support the humanities when so many people are suffering from the effects of the economic crisis? What claim do the humanities, or scholarship generally, have on increasingly limited resources? Shouldn't such pursuits be considered luxuries at a time when people should be focusing on essentials? The alleviation of human…

  13. Has human evolution stopped?

    PubMed

    Templeton, Alan R

    2010-07-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences. PMID:23908778

  14. Developments in Human Communication

    E-print Network

    Haykin, Simon

    CMST 1B03 Developments in Human Communication: Part & Present Amanda Etches-Johnson Mills Research in Human Communication Session Outline 1. Finding Books Using MORRIS 2. Finding Journal Articles using: Developments in Human Communication What is MORRIS anyway? · MORRIS is McMaster's library catalogue · Shows

  15. Human Genetics Portfolio Review

    E-print Network

    Rambaut, Andrew

    Human Genetics 1990­2009 June 2010 Portfolio Review #12;The Wellcome Trust is a charity registered in providing the assessments of the Wellcome Trust's role in supporting human genetics and have informed `our input to the development of the timelines. #12;Contents Portfolio Review: Human Genetics | 3

  16. Chimeras and Human Dignity

    Microsoft Academic Search

    2008-01-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman

  17. Portraits of Human Greatness.

    ERIC Educational Resources Information Center

    Saint Anselm's Coll., Manchester, NH.

    Examined is the Humanities Program at St. Anselm College, a two-year program of readings and lectures ordered chronologically from ancient to contemporary times--from the age of Classical Greek thought and the Old Testament to the twentieth century. The first year of the Humanities Program is organized in eight units on general modes of "human…

  18. The virtual physiological human

    E-print Network

    Narasayya, Vivek

    challenge: to use computational tech- niques to construct a model of how the human body works? Nuala Moran on each other and on the body ­ that are involved in the functioning of the human body. Now the Virtual and complexity of the human body. According to the roadmap for the project, drawn up under STEP (Strategy

  19. Human Rights and Capabilities

    Microsoft Academic Search

    Amartya Sen

    2005-01-01

    The two concepts — human rights and capabilities — go well with each other, so long as we do not try to subsume either concept entirely within the territory of the other. There are many human rights that can be seen as rights to particular capabilities. However, human rights to important process freedoms cannot be adequately analysed within the capability

  20. Glasgow Human Rights Network

    E-print Network

    Guo, Zaoyang

    ways in which people and communities can be a part of wider campaigns for equality and human rights. We and knowledge on the Commonwealth, international human rights, sexual orientation, gender identity and intersex working to uphold the human rights of lesbian, gay, bisexual and trans people internationally. www

  1. STUDENT EMPLOYMENT HUMAN RESOURCES

    E-print Network

    Gleixner, Stacy

    Programs and Services confirming the student is eligible to work. International students must provide HumanSTUDENT EMPLOYMENT HUMAN RESOURCES GUIDELINE Human Resources | One Washington Square | San José, CA / DESCRIPTION Student employees are defined as matriculated students that work part-time in any

  2. Human Research ProgramHuman Research Program Human System Risk in Exploration and

    E-print Network

    Waliser, Duane E.

    Human Research ProgramHuman Research Program Human System Risk in Exploration and the Human Research Program 21SEP10 1HRP Risk Process ­ D Grounds #12;Human Research ProgramHuman Research Program Human System Risks in Exploration Missions 21SEP10 2HRP Risk Process ­ D.Grounds Presentation contents

  3. Human Mitochondrial Protein Database

    National Institute of Standards and Technology Data Gateway

    SRD 131 Human Mitochondrial Protein Database (Web, free access)   The Human Mitochondrial Protein Database (HMPDb) provides comprehensive data on mitochondrial and human nuclear encoded proteins involved in mitochondrial biogenesis and function. This database consolidates information from SwissProt, LocusLink, Protein Data Bank (PDB), GenBank, Genome Database (GDB), Online Mendelian Inheritance in Man (OMIM), Human Mitochondrial Genome Database (mtDB), MITOMAP, Neuromuscular Disease Center and Human 2-D PAGE Databases. This database is intended as a tool not only to aid in studying the mitochondrion but in studying the associated diseases.

  4. Biological Races in Humans

    PubMed Central

    Templeton, Alan R.

    2013-01-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two most commonly used biological concepts of race, chimpanzees are indeed subdivided into races but humans are not. Adaptive traits, such as skin color, have frequently been used to define races in humans, but such adaptive traits reflect the underlying environmental factor to which they are adaptive and not overall genetic differentiation, and different adaptive traits define discordant groups. There are no objective criteria for choosing one adaptive trait over another to define race. As a consequence, adaptive traits do not define races in humans. Much of the recent scientific literature on human evolution portrays human populations as separate branches on an evolutionary tree. A tree-like structure among humans has been falsified whenever tested, so this practice is scientifically indefensible. It is also socially irresponsible as these pictorial representations of human evolution have more impact on the general public than nuanced phrases in the text of a scientific paper. Humans have much genetic diversity, but the vast majority of this diversity reflects individual uniqueness and not race. PMID:23684745

  5. carleton.ca Human Rights

    E-print Network

    Dawson, Jeff W.

    carleton.ca Human Rights #12;Human rights contribute, through theory and practice, to people and approaches from the humanities and social sciences, the Human Rights program provides an overview of historical and contemporary human rights issues and their impact on human lives in different cultural

  6. From human factors to human actors to human crafters

    Microsoft Academic Search

    Monica Maceli; Michael Atwood

    2011-01-01

    Meta-design theory emphasizes that future use can never be entirely anticipated at design time, as users shape their environments in response to emerging needs; systems should therefore be designed to adapt to future conditions in the hands of end users. For most of human history, all design was meta-design; designers were also users, and the environments of design and use

  7. Human research subjects as human research workers.

    PubMed

    Lynch, Holly Fernandez

    2014-01-01

    Biomedical research involving human subjects has traditionally been treated as a unique endeavor, presenting special risks and demanding special protections. But in several ways, the regulatory scheme governing human subjects research is counter-intuitively less protective than the labor and employment laws applicable to many workers. This Article relies on analogical and legal reasoning to demonstrate that this should not be the case; in a number of ways, human research subjects ought to be fundamentally recast as human research workers. Like other workers protected under worklaw, biomedical research subjects often have interests that diverge from those in positions of control but little bargaining power for change. Bearing these important similarities in mind, the question becomes whether there is any good reason to treat subjects and protected workers differently as a matter of law. With regard to unrestricted payment, eligibility for a minimum wage, compensation for injury, and rights to engage in concerted activity, the answer is no and human subjects regulations ought to be revised accordingly. PMID:25051653

  8. Humans Are Like Robots

    NSDL National Science Digital Library

    GK-12 Program, Computational Neurobiology Center,

    Four lessons related to robots and people present students with life sciences concepts related to the human body (including brain, nervous systems and muscles), introduced through engineering devices and subjects (including computers, actuators, electricity and sensors), via hands-on LEGO® robot activities. Students learn what a robot is and how it works, and then the similarities and differences between humans and robots. For instance, in lesson 3 and its activity, the human parts involved in moving and walking are compared with the corresponding robot components so students see various engineering concepts at work in the functioning of the human body. This helps them to see the human body as a system, that is, from the perspective of an engineer. Students learn how movement results from 1) decision making, such as deciding to walk and move, and 2) implementation by conveying decisions to muscles (human) or motors (robot).

  9. Nickel and human health.

    PubMed

    Zambelli, Barbara; Ciurli, Stefano

    2013-01-01

    This review focuses on the impact of nickel on human health. In particular, the dual nature of nickel as an essential as well as toxic element in nature is described, and the main forms of nickel that can come in contact with living systems from natural sources and anthropogenic activities are discussed. Concomitantly, the main routes of nickel uptake and transport in humans are covered, and the potential dangers that nickel exposure can represent for health are described. In particular, the insurgence of nickel-derived allergies, nickel-induced carcinogenesis as well as infectious diseases caused by human pathogens that rely on nickel-based enzymes to colonize the host are reviewed at different levels, from their macroscopic aspects on human health to the molecular mechanisms underlying these points. Finally, the importance of nickel as a beneficial element for human health, especially being essential for microorganisms that colonize the human guts, is examined. PMID:24470096

  10. Chimeras and human dignity.

    PubMed

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity. PMID:19143408

  11. Human Performance in Space

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  12. Human Ecology Theory

    Microsoft Academic Search

    Margaret M. Bubolz; M. Suzanne Sontag

    Human ecology theory is unique in its focus on humans as both biological organisms and social beings in interaction with their\\u000a environment.1 In this theory the family is considered to be an energy transformation system that is interdependent with its natural physical-biological,\\u000a human-built, and social-cultural milieu. Emphasis is given to the creation, use, and management of resources for creative\\u000a adaptation,

  13. Human reliability analysis

    SciTech Connect

    Dougherty, E.M.; Fragola, J.R.

    1988-01-01

    The authors present a treatment of human reliability analysis incorporating an introduction to probabilistic risk assessment for nuclear power generating stations. They treat the subject according to the framework established for general systems theory. Draws upon reliability analysis, psychology, human factors engineering, and statistics, integrating elements of these fields within a systems framework. Provides a history of human reliability analysis, and includes examples of the application of the systems approach.

  14. The Human Footprint

    NSDL National Science Digital Library

    The influence of humans on the land surface around the globe is represented through a series of maps. These maps are based on geographic proxies for drivers of human impact: human population density, land cover and land use mapping, lights regularly visible from a satellite at night, locations of roads, rivers and coasts, settlement patterns, etc. Sites are identified that represent the largest and relatively wildest places for various biomes. These 'last of the wild' sites are seen as conservation opportunities.

  15. Human organ markets and inherent human dignity.

    PubMed

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept. PMID:24979876

  16. Human Security Centre: Human Security Brief 2006

    NSDL National Science Digital Library

    While the concept of human security is a relatively new one, there is a growing consensus that the subject is one that will continue to be of the utmost importance in the coming years. Generally, the term is used to describe "the complex of interrelated threats associated with civil war, genocide and the displacement of populations." Recently, the Human Security Centre (located at the University of British Columbia) published its annual Human Security Brief, and placed it online at this site. The report analyzes the findings of several datasets that track trends in such areas as organized violence against civilians and the conclusion of armed conflicts worldwide. While this ambitious work does have some positive findings to announce, there are a number of other troubling trends, such as the fact that four of the world's six regions have experienced increased numbers of conflicts since 2002.

  17. Robotics for Human Exploration

    NASA Technical Reports Server (NTRS)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  18. Human Development Report 1997

    NSDL National Science Digital Library

    1997-01-01

    The United Nations Development Programme's Human Development Report Office provides two useful selections from its Human Development Report 1997. Overview of HDR 1997 is a detailed summary of the contents of the report, discussing world poverty and a six point strategy for poverty reduction. HDR 1997 Rankings contain Human Development Index, Gender-Related Development Index and Gender Empowerment Measure rankings tables for 175 countries. More detailed information on the meaning of the HDI is contained in Analytical Tools for Human Development. Full text of the report is forthcoming, and ordering information is available at the site.

  19. Human-Web Interactions

    NASA Astrophysics Data System (ADS)

    Géczy, Peter; Izumi, Noriaki; Akaho, Shotaro; Hasida, Kôiti

    Investigation of human behavior in electronic environments is rapidly gaining eminent position in web research. The driving forces of this endeavor originate from both commercial and scientific spheres. The commercial sector is eagerly exploring the human web behavior characteristics for amplifying and expanding the revenue generating possibilities. Novel trends in web development, as well as internet business models, unavoidably incorporate the elements of human-web interactions. The scientific inquiry into human web behavior is fundamentally oriented toward exploring, analyzing, understanding, modeling, and applying the findings.

  20. Human Research Tissues

    Cancer.gov

    Frederick National Laboratory for Cancer Research Pathology Histotechnology Laboratory Request # Human Sample Biosafety FormIn addition to this form, please complete the Pathology / Histology Request.Contact

  1. Human target acquisition performance

    NASA Astrophysics Data System (ADS)

    Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

    2012-06-01

    The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

  2. Reflecting on Human Reflexes

    NSDL National Science Digital Library

    2014-09-18

    Students learn about human reflexes, how our bodies react to stimuli and how some body reactions and movements are controlled automatically, without thinking consciously about the movement or responses. In the associated activity, students explore how reflexes work in the human body by observing an involuntary human reflex and testing their own reaction times using dominant and non-dominant hands. Once students understand the stimulus-to-response framework components as a way to describe human reflexes and reactions in certain situations, they connect this knowledge to how robots can be programmed to conduct similar reactions.

  3. Artificial human vision camera

    NASA Astrophysics Data System (ADS)

    Goudou, J.-F.; Maggio, S.; Fagno, M.

    2014-10-01

    In this paper we present a real-time vision system modeling the human vision system. Our purpose is to inspire from human vision bio-mechanics to improve robotic capabilities for tasks such as objects detection and tracking. This work describes first the bio-mechanical discrepancies between human vision and classic cameras and the retinal processing stage that takes place in the eye, before the optic nerve. The second part describes our implementation of these principles on a 3-camera optical, mechanical and software model of the human eyes and associated bio-inspired attention model.

  4. Human Genome Resources

    NSDL National Science Digital Library

    In an effort to track the progress of and provide access to the work of the Human Genome Project (see the October 14, 1998 Scout Report for Science & Engineering), the National Center for Biotechnology Information (NCBI) of the National Library of Medicine (NLM) has expanded their Web resource. An international research program "designed to construct detailed genetic and physical maps of the human genome." The Human Genome Resources page provides a wealth of relevant resources, from background information on the project, to specific sequences for each human chromosome (click on the desired chromosome), to Genome Maps of other organisms.

  5. The psychology of humanness.

    PubMed

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures. PMID:23947277

  6. Climate and Human Migrations

    NSDL National Science Digital Library

    Tom D. Dillehay (University of Kentucky; Department of Anthropology)

    2002-10-25

    Access to the article is free, however registration and sign-in are required. About 14,600 years ago, humans first appeared in south central Chile. But the arid regions of the Atacama desert in northern Chile were not populated for another 2000 years, and human occupation of this region subsequently remained intermittent. In his Perspective, Dillehay highlights the report of Núñez et al., whose integrative archaeological and paleoecological study shows that climate was the key factor in these human migrations. The study illustrates the power of an integrative approach to understanding the relation between human societies and climate change.

  7. Developing Human Resources through Actualizing Human Potential

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  8. HUMAN DIGNITY AND HUMAN REPRODUCTIVE CLONING

    Microsoft Academic Search

    Steven Malby

    2002-01-01

    he complexities and arguments both for and against human reproductive cloning (HRC) seem to have been discussed in almost every sphere imaginable. The worlds of law, medicine, science, bioethics, philosophy, and religion have all laid claim to the forum or framework in which the issues should be discussed. While public debate and the responses of national gov- ernments have been

  9. Human Powered Centrifuge

    NASA Technical Reports Server (NTRS)

    Mulenburg, Gerald M. (Inventor); Vernikos, Joan (Inventor)

    1997-01-01

    A human powered centrifuge has independently established turntable angular velocity and human power input. A control system allows excess input power to be stored as electric energy in a battery or dissipated as heat through a resistors. In a mechanical embodiment, the excess power is dissipated in a friction brake.

  10. THE HUMAN AUDITORY SYSTEM

    Microsoft Academic Search

    DAVID J M ROBINSON

    In this lecture, we will examine the apparatus used by a human to hear sound. These notes include the diagrams used within the lecture, as well as a description of the material covered. Further reading is suggested at the end. You will not be examined on the contents of this lecture, but knowledge of the human auditory system will aid

  11. Hooking Kids with Humanities.

    ERIC Educational Resources Information Center

    Anstead, Neil L.

    1993-01-01

    Humanitas is part of Collaboratives for Humanities and Arts Teaching (CHART), a nationwide network funded primarily by the Rockefeller Foundation. In 11 large school districts and numerous rural districts, high school teachers, academics, artists, and business and community leaders are cooperating to promote teaching of the arts and humanities

  12. Human pythiosis, Brazil.

    PubMed

    Bosco, Sandra de Moraes Gimenes; Bagagli, Eduardo; Araújo, João Pessoa; Candeias, João Manuel Grisi; de Franco, Marcello Fabiano; Alencar Marques, Mariangela Esther; Mendoza, Leonel; de Camargo, Rosangela Pires; Alencar Marques, Silvio

    2005-05-01

    Pythiosis, caused by Pythium insidiosum, occurs in humans and animals and is acquired from aquatic environments that harbor the emerging pathogen. Diagnosis is difficult because clinical and histopathologic features are not pathognomonic. We report the first human case of pythiosis from Brazil, diagnosed by using culture and rDNA sequencing. PMID:15890126

  13. Human Pythiosis, Brazil

    PubMed Central

    Bosco, Sandra de Moraes Gimenes; Araújo, João Pessoa; Candeias, João Manuel Grisi; Fabiano de Franco, Marcello; Marques, Mariangela Esther Alencar; Mendoza, Leonel; Pires de Camargo, Rosangela; Marques, Silvio Alencar

    2005-01-01

    Pythiosis, caused by Pythium insidiosum, occurs in humans and animals and is acquired from aquatic environments that harbor the emerging pathogen. Diagnosis is difficult because clinical and histopathologic features are not pathognomonic. We report the first human case of pythiosis from Brazil, diagnosed by using culture and rDNA sequencing. PMID:15890126

  14. Human Functional Brain Imaging

    E-print Network

    Rambaut, Andrew

    Human Functional Brain Imaging 1990­2009 September 2011 Portfolio Review Summary Brain Imaging #12 Dale ­ one of our first Trustees. Understanding the brain remains one of our key strategic aims today three-fold: · to identify the key landmarks and influences on the human functional brain imaging

  15. Evaluating the Humanities

    ERIC Educational Resources Information Center

    Brody, Howard

    2013-01-01

    How can one measure the value of teaching the humanities? The problem of assessment and accountability is prominent today, of course, in secondary and higher education. It is perhaps even more acute for those who teach the humanities in nontraditional settings, such as medical and other professional schools. The public assumes that academes can…

  16. Aging and Human Performance

    Microsoft Academic Search

    Neil Charness

    2008-01-01

    Objectives: I identify major theoretical and practical contributions to aging and human performance as reflected primarily in the pages of Human Factors.Background: Populations worldwide are aging. True experimental work on aging is not possible because age levels cannot be manipulated. Sophisticated theoretical frameworks and modeling techniques are required to reach valid inferences about age effects and age changes. Method: Citation

  17. Introduction to Human Genetics

    NSDL National Science Digital Library

    Sharon Nelson (Waunakee High School REV)

    1995-06-30

    The purpose of this lesson is to foster interest and enthusiasm for the study of human genetics with students. The lesson consists of a slide presentation showing everything from common human genetic tendencies (eye color, widow's peak, etc.) to polydactyly. Emphasis is placed on celebrating our differences, yet realizing how very much we all are alike.

  18. Introduction to human factors

    SciTech Connect

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  19. Manage "Human Capital" Strategically

    ERIC Educational Resources Information Center

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  20. Humanism within Globalization

    ERIC Educational Resources Information Center

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  1. Environment and the Humanities.

    ERIC Educational Resources Information Center

    Allen, Rodney F., Ed.; And Others

    As a conference report, the booklet is primarily devoted to abstracts of papers presented at a Conference on Environment and Humanities held in Tallahassee, Florida, April 25-27, 1976. Dr. Huston Smith of Syracuse University, the main speaker, addressed the issue of "Humanities and Environmental Awareness." Other topics discussed included: (1)…

  2. Dynamics of Human Behavior

    Microsoft Academic Search

    Douglas R. White

    I review network aspects of human dynamics that link macro-historical to micro- sociological and evolutionary processes. The ability to bond in communities of varying spatial scales is a special property of humans that happens through social networks. These networks have greater cohesion through invulnerability to disconnection without removal of k nodes. Menger's (1927) connectivity theorem shows that this property of

  3. Investigating the Human Experience

    ERIC Educational Resources Information Center

    Ducote, Richard L.; Peterson, Robert E.

    1975-01-01

    A project entitled "Investigating the Human Experience," which was funded by the National Endowment for the Humanities, enables the College of DuPage to conduct a series of free films in various off-campus facilities. Documentaries and recent TV specials are shown, followed by a group discussion moderated by an instructor from the college.…

  4. Quantifying Human Performance Reliability.

    ERIC Educational Resources Information Center

    Askren, William B.; Regulinski, Thaddeus L.

    Human performance reliability for tasks in the time-space continuous domain is defined and a general mathematical model presented. The human performance measurement terms time-to-error and time-to-error-correction are defined. The model and measurement terms are tested using laboratory vigilance and manual control tasks. Error and error-correction…

  5. Human Water Cycle

    NSDL National Science Digital Library

    Integrated Teaching and Learning Program,

    Students learn about the human water cycle, or how humans impact the water cycle by settling down in civilizations. Specifically, they learn how people obtain, use and dispose of water. Students also learn about shortages of treated, clean and safe water and learn about ways that engineers address this issue through water conservation and graywater recycling.

  6. The great human expansion.

    PubMed

    Henn, Brenna M; Cavalli-Sforza, L L; Feldman, Marcus W

    2012-10-30

    Genetic and paleoanthropological evidence is in accord that today's human population is the result of a great demic (demographic and geographic) expansion that began approximately 45,000 to 60,000 y ago in Africa and rapidly resulted in human occupation of almost all of the Earth's habitable regions. Genomic data from contemporary humans suggest that this expansion was accompanied by a continuous loss of genetic diversity, a result of what is called the "serial founder effect." In addition to genomic data, the serial founder effect model is now supported by the genetics of human parasites, morphology, and linguistics. This particular population history gave rise to the two defining features of genetic variation in humans: genomes from the substructured populations of Africa retain an exceptional number of unique variants, and there is a dramatic reduction in genetic diversity within populations living outside of Africa. These two patterns are relevant for medical genetic studies mapping genotypes to phenotypes and for inferring the power of natural selection in human history. It should be appreciated that the initial expansion and subsequent serial founder effect were determined by demographic and sociocultural factors associated with hunter-gatherer populations. How do we reconcile this major demic expansion with the population stability that followed for thousands years until the inventions of agriculture? We review advances in understanding the genetic diversity within Africa and the great human expansion out of Africa and offer hypotheses that can help to establish a more synthetic view of modern human evolution. PMID:23077256

  7. Enhancing Portugal's Human Capital

    Microsoft Academic Search

    Stéphanie Guichard; Bénédicte Larre

    2006-01-01

    The lack of human capital in Portugal has become a key obstacle to higher growth. This paper discusses the performance of education and training services in Portugal and shows that improvements are needed to narrow the significant human capital gap with other OECD countries. Despite progress in the past decades, Portuguese children spend comparatively few years in formal education, and

  8. WORKPLACE VIOLENCE HUMAN RESOURCES

    E-print Network

    Su, Xiao

    WORKPLACE VIOLENCE HUMAN RESOURCES POLICY Human Resources | One Washington Square | San José, CA 95192-0046 | 408-924-2250 408-924-1701 (fax) SUBJECT: WORKPLACE VIOLENCE POLICY DATE: April 2008/or property. San José State University takes a "zero tolerance" stance regarding workplace violence. Workplace

  9. Methods in human cytogenetics

    SciTech Connect

    NONE

    1993-12-31

    Chapter 4, discusses the various techniques used in the study human cytogenetics. The methods are discussed in historical order, from direct methods to tissue culture techniques, prenatal studies, meiotic studies, sex chromatin techniques, banding techniques, prophase banding and replication studies. Nomenclature of human chromosomes and quantitative methods are also mentioned. 60 refs., 3 figs.

  10. Future Evolution of Humanity

    Microsoft Academic Search

    Linda Groff

    2007-01-01

    The future evolution of humanity is a huge topic. There are a number of factors that will influence the future evolution of humanity, including how people view and deal with change in general; different models of the processes of evolution and change transforming our world, and different substantive stages of evolution - in physical, biological, cultural, technological, and consciousness areas

  11. Immunology Taught by Humans

    PubMed Central

    Davis, Mark M.

    2013-01-01

    After a half-century of mouse-dominated research, human immunology is making a comeback. Informed by mouse studies and powered by new techniques, human immune research is both advancing disease treatment and providing new insights into basic biology. PMID:22261029

  12. HEALTH AND HUMAN RIGHTS

    Microsoft Academic Search

    Jonathan M. Mann; Sofia Gruskin; MIA Troyen Brennan; Harvey V Fineberg

    1994-01-01

    H ealth and human rights have rarely been linked in an ex- plicit manner. With few exceptions, notably involving access to health care, discussions about health have rarely.included hu- man rights considerations. Similarly, except when obvious dam- age to health is the primary manifestation of a human rights abuse, such as with torture, health perspectives have been gen- erally absent

  13. Being Human in Sport.

    ERIC Educational Resources Information Center

    Allen, Dorothy J.; Fahey, Brian W.

    The structure of humanness as the unique and essential being of the individual, constantly emerging through experience and the actualization of human potential within the sports environment, is the central theme of this book. Sport is defined broadly to include all forms of physical activity experiences. Each chapter represents an inquiry unique…

  14. HUMAN CARCINOGENESIS BY ARSENIC

    EPA Science Inventory

    Arsenic is one of the few human carcinogens for which there is not yet a reliable animal cancer model. s such, the classification of arsenic as a carcinogen is based upon data derived from human epidemiologic studies. Although the mechanisms of action of arsenic as a toxic agent ...

  15. Healthline Human Body Maps

    NSDL National Science Digital Library

    Healthline (Healthline Networks Inc)

    2005-01-01

    This website provides a 3-D animation of the human body. The animation allows visitors to view a variety of layers of the human body organized by both system and organs. In addition, health information, articles, and structures can be found with each layer. The website is also searchable by specific structure.

  16. Humanity's unsustainable environmental footprint

    E-print Network

    Napp, Nils

    on the size and spatiotemporal characteristics of humanity's footprint relative to Earth's car- rying capacityREVIEW Humanity's unsustainable environmental footprint Arjen Y. Hoekstra1* and Thomas O. Wiedmann2,3 Within the context of Earth's limited natural resources and assimilation capacity, the current

  17. Human immune interferon

    SciTech Connect

    Goeddel, D.V.; Gray, P.

    1988-02-23

    This patent describes a molecule consisting of a DNA molecule encoding the amino acid sequence of recombinant human immune interferon. It describes a molecule consisting essentially of a DNA molecule encoding the amino acid sequence of des-CYS-TYR-CYS recombinant human immune interferon.

  18. Quantification of human responses

    NASA Technical Reports Server (NTRS)

    Steinlage, R. C.; Gantner, T. E.; Lim, P. Y. W.

    1992-01-01

    Human perception is a complex phenomenon which is difficult to quantify with instruments. For this reason, large panels of people are often used to elicit and aggregate subjective judgments. Print quality, taste, smell, sound quality of a stereo system, softness, and grading Olympic divers and skaters are some examples of situations where subjective measurements or judgments are paramount. We usually express what is in our mind through language as a medium but languages are limited in available choices of vocabularies, and as a result, our verbalizations are only approximate expressions of what we really have in mind. For lack of better methods to quantify subjective judgments, it is customary to set up a numerical scale such as 1, 2, 3, 4, 5 or 1, 2, 3, ..., 9, 10 for characterizing human responses and subjective judgments with no valid justification except that these scales are easy to understand and convenient to use. But these numerical scales are arbitrary simplifications of the complex human mind; the human mind is not restricted to such simple numerical variations. In fact, human responses and subjective judgments are psychophysical phenomena that are fuzzy entities and therefore difficult to handle by conventional mathematics and probability theory. The fuzzy mathematical approach provides a more realistic insight into understanding and quantifying human responses. This paper presents a method for quantifying human responses and subjective judgments without assuming a pattern of linear or numerical variation for human responses. In particular, quantification and evaluation of linguistic judgments was investigated.

  19. The human genome project

    Microsoft Academic Search

    Thomas D. Yager; Thomas E. Zewert; Leroy E. Hood

    1994-01-01

    The Human Genome Project (HGP) is a coordinated worldwide effort to precisely map the human genome and the genomes of selected model organisms. The first explicit proposal for this project dates from 1985 although its foundations (both conceptual and technological) can be traced back many years in genetics, molecular biology, and biotechnology. The HGP has matured rapidly and is producing

  20. Human Sociobiology: Wilson's Fallacy.

    ERIC Educational Resources Information Center

    Lehrman, Nathaniel S.

    1981-01-01

    Presents an introduction to and a critique of E.O. Wilson's new science of sociobiology, which focuses on explaining the social behavior of species as diverse as ants, apes, and humans. Suggests that Wilson has gone beyond his data in claiming that complex human behaviors such as altruism are caused to any extent by genetic, as opposed to…

  1. Neuroergonomics and human error

    Microsoft Academic Search

    John R. Fedota; Raja Parasuraman

    2010-01-01

    Neuroergonomics complements traditional ergonomic approaches to understanding many aspects of human–system performance, including the analysis of human error. This paper reviews the evidence on neural signals associated with different error types, specifically the error-related negativity (ERN), a brain potential that is extracted from the scalp electroencephalogram and that is generated in a medial prefrontal brain region, the anterior cingulate cortex.

  2. Beliefs about Human Extinction

    SciTech Connect

    Tonn, Bruce Edward [ORNL

    2009-11-01

    This paper presents the results of a web-based survey about futures issues. Among many questions, respondents were asked whether they believe humans will become extinct. Forty-five percent of the almost 600 respondents believe that humans will become extinct. Many of those holding this believe felt that humans could become extinct within 500-1000 years. Others estimated extinction 5000 or more years into the future. A logistic regression model was estimated to explore the bases for this belief. It was found that people who describe themselves a secular are more likely to hold this belief than people who describe themselves as being Protestant. Older respondents and those who believe that humans have little control over their future also hold this belief. In addition, people who are more apt to think about the future and are better able to imagine potential futures tend to also believe that humans will become extinct.

  3. The human ecology of parks

    Microsoft Academic Search

    Gary E. Machlis; Donald R. Field; Fred L. Campbell

    1981-01-01

    This paper explores a human ecological approach to the study of people and parks. A human ecological perspective is outlined, along with the key units of analysis in human ecology. A theoretical framework for treating parks as human ecosystems is developed. Several ecological processes relevant to understanding human activity within parks are discussed, including adaptation, competition, and succession. The paper

  4. The Concept of Being Human.

    ERIC Educational Resources Information Center

    Purcell, Royal

    This analysis of the relationship between humanism and humanitarianism outlines educational goals that should lead to a more humane world. Section 1, an outline of human life examines six substructures--human life, individuality, amenity, contact, actualization, and problems. A definition and examples of humanism in section 2 are elaborated into a…

  5. HUMAN RESOURCE MANAGEMENT Human resource management is the process of

    E-print Network

    , entrepreneurship, finance, international business, management, management information systems, marketing5/2013 HUMAN RESOURCE MANAGEMENT Human resource management is the process of attracting the most. Human resource management professionals also design and oversee the use of performance appraisal systems

  6. [On bedside medical humanities].

    PubMed

    Barilan, M; Sharon, D

    2001-12-01

    This article presents a challenge which we call "the humane gap in medicine" and also raises some ideas on how to meet this challenge. This is the gap between the capacities of biomedicine as a bureaucratic and scientific establishment and the medical needs and expectations of its beneficiaries. It is argued that successful medicine relies on two pillars. The first is the corpus of biomedical knowledge, while the other is knowing the patients within their bio-psycho-social life-world. Both the second pillar and the bridging of the two pillars are dependent on the Humanities. The humanities in medicine also provide healthcare professionals with means of support against devastating encounters with suffering, disability or the relentless pressures of academic careers and overwhelming physical labor. The humanities serve as a shared platform for all healthcare providers, diminishing traditional, and sometimes obstructive, boundaries such as those that may exist between doctors and nurses. We provide a list of possible benefits that the Humanities may bring to clinical practice and medical education. We conclude with some suggestions on how the humanities may be incorporated into medical education and implemented at the bedside. We suggest that art students attend anatomical labs; courses in medical humanities be opened for the benefit of all students, within the faculty of medicine and beyond. We encourage students from every faculty to undertake academic activities which will combine voluntary work with the sick with participatory observation in the tradition of cultural anthropology. PMID:11789308

  7. Human Space Exploration

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Antony

    2014-01-01

    The Mars probe, launched by India a few months ago, is on its way to Mars. At this juncture, it is appropriate to talk about the opportunities presented to us for the Human Exploration of Mars. I am planning to highlight some of the challenges to take humans to Mars, descend, land, stay, ascend and return home safely. The logistics of carrying the necessary accessories to stay at Mars will be delivered in multiple stages using robotic missions. The primary ingredients for human survival is air, water, food and shelter and the necessity to recycle the primary ingredients will be articulated. Humans have to travel beyond the van Allen radiation belt under microgravity condition during this inter-planetary travel for about 6 months minimum one way. The deconditioning of human system under microgravity conditions and protection of humans from Galactic cosmic radiation during the travel should be taken into consideration. The multi-disciplinary effort to keep the humans safe and functional during this journey will be addressed.

  8. Habitability and Human Factors Contributions to Human Space Flight

    NASA Technical Reports Server (NTRS)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  9. HUMAN GROSS ANATOMY ANTH 695

    E-print Network

    Auerbach, Benjamin M.

    1 HUMAN GROSS ANATOMY ANTH 695 THE UNIVERSITY OF TENNESSEE Instructor lectures: 33 ALUMNI MEMORIAL BUILDING Course description: Human Gross Anatomy knowledge) is also stressed. Course textbooks: Human gross anatomy uses four

  10. Associate Vice President Human Resources

    E-print Network

    Arnold, Jonathan

    Associate Vice President Human Resources Enjoy Athens! Great schools Affordable housing Eclectic Vice President for Human Resources. This position reports directly to the Vice President for Finance and Administration and provides leadership for the University's human resources programs and services

  11. UNDERGRADUATE STUDENT MANUAL HUMAN PHYSIOLOGY

    E-print Network

    Guenther, Frank

    UNDERGRADUATE STUDENT MANUAL FOR HUMAN PHYSIOLOGY 2011-2012 Revised: September, 2011 (JLS) #12;- 2 ................................................................................................................. - 3 - II. INTRODUCTION TO THE DEPARTMENT OF HEALTH SCIENCES PROGRAM IN HUMAN PHYSIOLOGY........................................................................................................................................ - 4 - III. FULL-TIME FACULTY IN HUMAN PHYSIOLOGY

  12. UNDERGRADUATE STUDENT MANUAL HUMAN PHYSIOLOGY

    E-print Network

    Guenther, Frank

    UNDERGRADUATE STUDENT MANUAL FOR HUMAN PHYSIOLOGY 2012-2013 Revised: September, 2012 (JLS) #12;- 2 ................................................................................................................. - 3 - II. INTRODUCTION TO THE DEPARTMENT OF HEALTH SCIENCES PROGRAM IN HUMAN PHYSIOLOGY........................................................................................................................................ - 4 - III. FULL-TIME FACULTY IN HUMAN PHYSIOLOGY

  13. HUMAN SERVICES Mental Health Services

    E-print Network

    Escher, Christine

    courses. HUMAN RESOURCES Employment and Recruitment Labor Relations Compensation and Benefits Public chapter of Public Relations Society of America. Human Resources (Personnel) depart- ments of companiesPSYCHOLOGY HUMAN SERVICES Counseling Advocacy Mental Health Services STRATEGIESAREAS EMPLOYERS

  14. HUMAN RESOURCES SIMON FRASER UNIVERSITY

    E-print Network

    HUMAN RESOURCES SIMON FRASER UNIVERSITY ADMINISTRATIVE AND PROFESSIONAL STAFF POSITION DESCRIPTION the management of departmental resources including: financial, human resources, facilities, and administrative or Associate Dean, and liaises with University administrators, other universities, finance, and human resources

  15. Human Resources Simon Fraser University

    E-print Network

    Kavanagh, Karen L.

    Human Resources Simon Fraser University Administrative and Professional Staff Job Description A. Identification Position Number: 31482 Position Title: Administrative Assistant (Human Resources Liaison) Name guidance, direction, coordination and effective management and implementation of SFU's Human Resources

  16. HUMAN SUBJECT PAYMENTS Policy Statement

    E-print Network

    Shahriar, Selim

    Page 1 HUMAN SUBJECT PAYMENTS Policy Statement This policy outlines the requirements for Northwestern University to comply with requirements of the Human Subject Protection Program (HSPP), University Human Resource policies and practices, the Internal Revenue Service (IRS), and University purchasing

  17. Office for Human Research Protections

    MedlinePLUS

    ... OHRP Text Size: A A A Office for Human Research Protections (OHRP) The Office for Human Research ... Research conference. HHS August 28, 2013 Meeting on Human Subjects Protections View meeting agenda View meeting presentations ...

  18. Special Issue on Human Computing

    E-print Network

    Nijholt, Anton

    The seven articles in this special issue focus on human computing. Most focus on two challenging issues in human computing, namely, machine analysis of human behavior in group interactions and context-sensitive modeling.

  19. Human Computer Interaction

    NASA Astrophysics Data System (ADS)

    Bhagwani, Akhilesh; Sengar, Chitransh; Talwaniper, Jyotsna; Sharma, Shaan

    2012-08-01

    The paper basically deals with the study of HCI (Human computer interaction) or BCI(Brain-Computer-Interfaces) Technology that can be used for capturing brain signals and translating them into commands that allow humans to control (just by thinking) devices such as computers, robots, rehabilitation technology and virtual reality environments. The HCI is based as a direct communication pathway between the brain and an external device. BCIs are often aimed at assisting, augmenting, or repairing human cognitive or sensory-motor functions.The paper also deals with many advantages of BCI Technology along with some of its applications and some major drawbacks.

  20. Human Rights in China

    NSDL National Science Digital Library

    Created in 1989, Human Rights in China is one of the major sources of information on human rights conditions in the People's Republic of China. The site offers press releases, reports, articles from its quarterly journal, China Rights Forum, organizational work reports, educational materials, action ideas and related links. In addition, the site covers a number of topics, including political prisoners and dissent, legal reform, freedom of association, women's rights, workers' rights, children's rights, and human rights education. The entire site is also available in Chinese.

  1. Redrawing Humanity's Family Tree

    NSDL National Science Digital Library

    Wilford, John Noble

    This New York Times article details two skulls, one from central Africa and the other from the Black Sea republic of Georgia, that "have shaken the human family tree to its roots, sending scientists scrambling to see if their favorite theories are among the fallen fruit." The article discusses how the two skulls have caused scientists to rethink not only how we conceive of human evolution and its chain of events, but even the geography of evolution and migration patterns of very early humans.

  2. Viruses and human cancer

    SciTech Connect

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  3. Human Resource Planning

    ERIC Educational Resources Information Center

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  4. Human Reliability Program Overview

    SciTech Connect

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  5. Approaches to Human Communication.

    ERIC Educational Resources Information Center

    Budd, Richard W., Ed.; Ruben, Brent D., Ed.

    This anthology of essays approaches human communication from the points of view of: anthropology, art biology, economics, encounter groups, semantics, general system theory, history, information theory, international behavior, journalism, linguistics, mass media, neurophysiology, nonverbal behavior, organizational behavior, philosophy, political…

  6. Human intelligible positioning

    E-print Network

    Venugopalan, Vishwanath, 1981-

    2004-01-01

    We use street addresses to refer to locations in a city. Street addresses are easy to remember and communicate because they follow a symbolic addressing scheme, containing human intelligible symbols. However, street addresses ...

  7. The Human Mycobiome.

    PubMed

    Seed, Patrick C

    2014-11-10

    Fungi are fundamental to the human microbiome, the collection of microbes distributed across and within the body, and the microbiome has been shown, in total, to modify fundamental human physiology, including energy acquisition, vitamin-cofactor availability, xenobiotic metabolism, immune development and function, and even neurological development and behavior. Here, a comprehensive review of current knowledge about the mycobiome, the collective of fungi within the microbiome, highlights methods for its study, diversity between body sites, and dynamics during human development, health, and disease. Early-stage studies show interactions between the mycobiome and other microbes, with host physiology, and in pathogenic and mutualistic phenotypes. Current research portends a vital role for the mycobiome in human health and disease. PMID:25384764

  8. Human teeth model

    NSDL National Science Digital Library

    Håkan Svensson (None; )

    2005-12-23

    Humans are omnivores, meaning they eat both meat and plants. Omnivores generally have a mix of canines to shred meat and flat teeth to grind vegetation. The canines are less sharp than those seen in strict meat-eaters.

  9. Human Resources & Rebecca Leinen

    E-print Network

    Acton, Scott

    Work Management Mark Webb Systems Engineering Office for Sustainability Maintenance Landscape Energy & Utilities Building Services Automation Services Engineering & Design Academic Division Health SystemsHuman Resources & Training Rebecca Leinen Safety Laura Duckworth Information Systems Chris Smeds

  10. Antihemophilic Factor (Human)

    MedlinePLUS

    Your doctor has ordered antihemophilic factor (human), an antihemophilic factor, to help your blood to clot. The drug will be either injected directly into your vein or added to an intravenous fluid ...

  11. HPV (Human Papillomavirus)

    MedlinePLUS

    ... and Share (PDF 1105 KB ) En Español HPV (human papillomavirus) is a sexually transmitted virus. It is passed on through genital contact (such as vaginal and anal sex). It is also passed on by skin-to- ...

  12. Human X chromosome

    SciTech Connect

    NONE

    1993-12-31

    Chapter 21, describes in detail the human X chromosome. X chromatin (or Barr body) formation, inactivation and reactivation of the X chromosome, X;Y translocations, and sex reversal are discussed. 30 refs., 3 figs.

  13. What makes us human?

    E-print Network

    Mikkelsen, Tarjei S.

    The sequence of chimpanzee chromosome 22 is starting to help us to define the set of genetic attributes that are unique to humans, but interpreting the biological consequences of these remains a major challenge.

  14. The Human Hazard.

    ERIC Educational Resources Information Center

    Tickell, Crispin

    1995-01-01

    Examines the plight of environmental refugees and the adequacy of political responses to the situation. Discusses the consequences of accelerated environmental change, particularly the impact of global warming on human migration. (LZ)

  15. Backyard Burning: Human Health

    MedlinePLUS

    ... lasting substances that can build up in the food chain to levels that are harmful to human and ecosystem health. Persistent means they remain in the environment for extended periods of time. Bioaccumulative means their ...

  16. Human Genome Center

    NSDL National Science Digital Library

    Human Genome Center At Lawrence Berkeley Lab (LBL), Berkeley, California: offering information about projects in Biology, Informatics and Instrumentation, photos of LBL robotic instruments, software, and online access to one LBL genomic database.

  17. Aerospace Human Factors

    NASA Technical Reports Server (NTRS)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  18. HUMAN SERVICES Direct Care

    E-print Network

    Mountziaris, T. J.

    Services Physical Health and Wellness Crisis Work Art Therapy Music Therapy Administration: AdvocacyPSYCHOLOGY HUMAN SERVICES Direct Care: Counseling Psychotherapy Case Management Mental Health specialties exist at the graduate level, for example school counseling, mental health counseling, counseling

  19. Teaching about Human Geography.

    ERIC Educational Resources Information Center

    Schlene, Vickie J.

    1991-01-01

    Presents a sampling of items from the ERIC database concerning the teaching of human geography. Includes documents dealing with Africa, Asia, the United States, Canada, Antarctica, and geographic concepts. Explains how to obtain ERIC documents. (SG)

  20. Human Functional Brain Imaging

    E-print Network

    Rambaut, Andrew

    forward: speculations on the future of human functional brain imaging 30 4.1 More solution-focused, October 2009 1. The Wellcome Trust has provided substantial funding for neuroscience and mental health

  1. Pushing Human Frontiers

    NASA Technical Reports Server (NTRS)

    Zubrin, Robert

    2005-01-01

    With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

  2. Human Assisted Assembly Processes

    SciTech Connect

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative automation has shown the effectiveness of humans and machines directly interacting to perform tasks. To continue to advance this area of robotics, effective means need to be developed to allow natural ways for people to communicate and cooperate with robots just as they do with one another.

  3. Human and Robot Sensors

    NSDL National Science Digital Library

    GK-12 Program, Computational Neurobiology Center,

    Students are provided with a rigorous background in human "sensors" (including information on the main five senses, sensor anatomies, and nervous system process) and their engineering equivalents, setting the stage for three associated activities involving sound sensors on LEGO® robots. As they learn how robots receive input from sensors, transmit signals and make decisions about how to move, students reinforce their understanding of the human body's sensory process.

  4. Mapping the human genome

    SciTech Connect

    Annas, G.C.; Elias, S. (eds.)

    1992-01-01

    This article is a review of the book Mapping the Human Genome: Using Law and Ethics as Guides, edited by George C. Annas and Sherman Elias. The book is a collection of essays on the subject of using ethics and laws as guides to justify human gene mapping. It addresses specific issues such problems related to eugenics, patents, insurance as well as broad issues such as the societal definitions of normality.

  5. Human–Bird Interactions

    Microsoft Academic Search

    Patricia K. Anderson

    \\u000a The human–bird relationship is diverse and varies between cultures and within the same cultures over time. Humans have exploited\\u000a various avian species for millennia, using them for many different purposes including their flesh and eggs as food, skins\\u000a and feathers as clothing, egg shells and feathers (including whole taxidermied birds) as decorative items, feathers as quill\\u000a pens or as fletching

  6. Visible Earth: Human Dimensions

    NSDL National Science Digital Library

    This website is part of Visible Earth, which is hosted by the National Aeronautics and Space Administration (NASA), and contains a searchable directory of images, visualizations, and animations of the Earth. This section pertains to human impact on the Earth, and includes images in the following categories: boundaries, land use/land cover, economic resources, environmental impacts, human health, infrastructure, and population. Each image is available in a variety of resolutions and sizes, with a brief description, credit, date, and photographing satellite.

  7. Human ocular anatomy.

    PubMed

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

    2015-01-01

    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes. PMID:25704934

  8. Quality and human society

    NASA Astrophysics Data System (ADS)

    Stoll, W.

    1991-02-01

    Quality of products and services is seen as a necessity in our modern world. Quality also has important cross-links to safety in our society. It is however suggested, that human beings are living in their industrial environment under the stress of a fractured personality with anxieties and frustrations. Some cultural comparisons with other industrial nations are given. Quality control tailored to human nature is recommended.

  9. Human facial beauty

    Microsoft Academic Search

    Randy Thorrthill; Steven W. Gangestad

    1993-01-01

    It is hypothesized that human faces judged to be attractive by people possess two features—averageness and symmetry—that promoted\\u000a adaptive mate selection in human evolutionary history by way of production of offspring with parasite resistance. Facial composites\\u000a made by combining individual faces are judged to be attractive, and more attractive than the majority of individual faces.\\u000a The composites possess both symmetry

  10. The great human expansion

    PubMed Central

    Henn, Brenna M.; Cavalli-Sforza, L. L.; Feldman, Marcus W.

    2012-01-01

    Genetic and paleoanthropological evidence is in accord that today’s human population is the result of a great demic (demographic and geographic) expansion that began approximately 45,000 to 60,000 y ago in Africa and rapidly resulted in human occupation of almost all of the Earth’s habitable regions. Genomic data from contemporary humans suggest that this expansion was accompanied by a continuous loss of genetic diversity, a result of what is called the “serial founder effect.” In addition to genomic data, the serial founder effect model is now supported by the genetics of human parasites, morphology, and linguistics. This particular population history gave rise to the two defining features of genetic variation in humans: genomes from the substructured populations of Africa retain an exceptional number of unique variants, and there is a dramatic reduction in genetic diversity within populations living outside of Africa. These two patterns are relevant for medical genetic studies mapping genotypes to phenotypes and for inferring the power of natural selection in human history. It should be appreciated that the initial expansion and subsequent serial founder effect were determined by demographic and sociocultural factors associated with hunter-gatherer populations. How do we reconcile this major demic expansion with the population stability that followed for thousands years until the inventions of agriculture? We review advances in understanding the genetic diversity within Africa and the great human expansion out of Africa and offer hypotheses that can help to establish a more synthetic view of modern human evolution. PMID:23077256

  11. The human oncogenic viruses

    SciTech Connect

    Luderer, A.A.; Weetall, H.H

    1986-01-01

    This book contains eight selections. The titles are: Cytogenetics of the Leukemias and Lymphomas; Cytogenetics of Solid Tumors: Renal Cell Carcinoma, Malignant Melanoma, Retinoblastoma, and Wilms' Tumor; Elucidation of a Normal Function for a Human Proto-Oncogene; Detection of HSV-2 Genes and Gene Products in Cervical Neoplasia; Papillomaviruses in Anogennital Neoplasms; Human Epstein-Barr Virus and Cancer; Hepatitis B Virus and Hepatocellular Carcinoma; and Kaposi's Sarcoma: Acquired Immunodeficiency Syndrome (AIDS) and Associated Viruses.

  12. Human Development Report 2005

    NSDL National Science Digital Library

    2005-01-01

    The notion of human development is one that is quite old, even if it has not always gone by that name. The United Nations understands human development to be about â??creating an environment in which people can develop their full potential and lead productive, creative lives in accord with their needs and interestsâ?. In this way, of course, many ancient city-states and other such communities of shared interests have always been about creating such an environment. This latest report on the state of human development affords curious individuals an insight into the United Nationsâ?? work in this area. It offers some insights into the nature of inequalities which affect the potentiality of human development schemes and also looks at other related processes such as the nature of international trade and violent conflict. The report is divided into five primary chapters, and is supplemented by a list of human development indicators and a bibliography. The site also contains an animated file that offers a visualization of the trend of human development.

  13. Human Factors Review Plan

    SciTech Connect

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  14. Immunogenetics of Human Placentation

    PubMed Central

    Parham, Peter; Norman, Paul J.; Abi-Rached, Laurent; Hilton, Hugo G.; Guethlein, Lisbeth A.

    2013-01-01

    Natural killer (NK) cells are a population of lymphocytes that function in both immune defense and reproduction. Diversifying NK cell phenotype and function are interactions between NK cell receptors and major histocompatibility complex (MHC) class I ligands. As a consequence of strong and variable selection these ligand-receptor systems are polymorphic, rapidly evolving, and considerably species-specific. Counterparts to the human system of HLA class I ligands and killer cell immunoglobulin-like receptors (KIR) are present only in apes and Old World monkeys. HLA-C, the dominant ligand for human KIR and the only polymorphic HLA class I expressed by trophoblast, is further restricted to humans and great apes. Even then, the human system appears qualitatively different from that of chimpanzees, in that it has evolved a genetic balance between particular groups of receptors and ligands that favor reproductive success and other groups of receptors and ligands that have been correlated with disordered placentation. Human populations that have survived successive episodes of epidemic disease and population bottlenecks maintain a breadth of diversity for KIR and HLA class I, implying that loss of such diversity disfavors long-term survival of a human population. PMID:22177321

  15. Glycobiology of human milk.

    PubMed

    Newburg, D S

    2013-07-01

    Glycans are characteristic components of milk, and each species has unique patterns of specific carbohydrates. Human milk is unusually rich in glycans, with the major components being lactose and oligosaccharides, representing approximately 6.8 and 1% of the milk, respectively. Other sources of glycans in human milk include monosaccharides, mucins, glycosaminoglycans, glycoproteins, glycopeptides, and glycolipids. In human milk, the presence and patterns of these glycans vary depending upon the stage of lactation and the maternal genes and their genetic polymorphisms that control glycosyl transferases. The synthesis of milk glycans utilizes a significant portion of the metabolic energy that the mother expends when producing her milk, but other than lactose, these glycans contribute little to the nutritional needs of the infant. The data herein support several functions. 1) Many human milk glycans inhibit pathogens from binding to the intestinal mucosa. 2) Human milk glycans attenuate inflammation. 3) Glycans also directly stimulate the growth of beneficial (mutualist) bacteria of the microbiota (formerly considered commensal microflora of the intestine); these mutualists and their fermentation products can, in turn, (a) inhibit pathogens, (b) modulate signaling and inflammation, and (c) the fermentation products can be absorbed and utilized as a source of dietary calories. These functions can help direct and support intestinal postnatal growth, development, and ontogeny of colonization. The many functions of the milk glycans may synergistically protect infants from disease. Hence, human milk glycans and their homologs may serve as novel prophylactic or therapeutic agents for a diverse range of deleterious conditions. PMID:24010840

  16. [Atypical human trypanosomoses].

    PubMed

    Truc, P; Nzoumbou-Boko, R; Desquesnes, M; Semballa, S; Vincendeau, P

    2014-01-01

    Trypanosomes are principally responsible for two human diseases: human African trypanosomiasis (HAT) or sleeping sickness (caused by Trypanosoma brucei gambiense and T. b. rhodesiense), and Chagas disease, also called South American trypanosomiasis (T. cruzi). However, some trypanosomes that are natural parasites only of animals can sometimes infect humans and cause the so-called "atypical human trypanosomiases" (aHT). T. evansi, the agent causing surra in camels, horses, dogs, and bovines, and T. lewisi, a cosmopolite rat parasite, are the most frequently involved. These atypical infections involve no or only minor symptoms, but major symptoms are sometimes present. Parasite elimination is generally spontaneous, but can require treatment. Molecular tools, such as polymerase chain reaction, have improved the accuracy of parasite identification. Immunological techniques, mainly immunoenzymatic assays, can detect asymptomatic subjects. Several causes, most often concomitant, have been hypothesized, including immune immaturity, immunodeficiency, and close contact with infected animals. Innate immunity to animal trypanosomes depends on a trypanolytic factor called apolipoprotein L-I, present in human serum. A deficit in both apolipoprotein L-I alleles has been reported in an Indian patient infected by T. evansi. The prevalence of aHT is probably underestimated. Moreover, these trypanosomes might become potential emerging zoonotic pathogens, due to their ability to invade new hosts. An international network has been set up to survey these aHT (NAHIAT: Network on Atypical Human Infections by Animal Trypanosomes). PMID:24918468

  17. The Universal Declaration on the Human Genome and Human Rights

    Microsoft Academic Search

    Federico Mayor

    2003-01-01

    Since 1985, UNESCO studies ethical questions arising in genetics. In 1992, I established the International Bioethics Committee at UNESCO with the mission to draft the Universal Declaration on the Human Genome and Human Rights, which was adopted by UNESCO in 1997 and the United Nations in 1998. The Declaration relates the human genome with human dignity, deals with the rights

  18. Science and the humanities: the case for state humanities councils

    Microsoft Academic Search

    G. M. Leftwich

    2002-01-01

    Although joined together by their commitment to inquiry, in their pursuit of seemingly divergent goals science and the humanities sometimes appear to be in tension. This article suggests that the public humanities programs sponsored by state humanities councils, the independent nonprofit state affiliates of the National Endowment for the Humanities, serve as vehicles for reconciling the differing concerns of science

  19. 227Poverty and Human Capability Studies Poverty AND HUMAN

    E-print Network

    Dresden, Gregory

    227Poverty and Human Capability Studies Poverty AND HUMAN CAPABILIty StUDIeS (Pov) Core FACULty and Human Capability offers a cur- ricularandcocurricularprogramofstudythatenrichesany major. Sustained and establishing a decent minimum of human development for all people. Students completing desig- nated

  20. Human Pathogen Importation Importing "Human" Pathogens from Outside Canada

    E-print Network

    Human Pathogen Importation Importing "Human" Pathogens from Outside Canada 1) Permits.gc.ca/ols-bsl/pathogen/index.html and scroll to the bottom of the page where you can download the "Application for Permit to Import Human Human Pathogens" and "CL2 Checklist" to PHAC at (613) 941-0596. There are no fees for this service. 5

  1. Infants' Responses to Real Humans and Representations of Humans

    ERIC Educational Resources Information Center

    Heron, Michelle; Slaughter, Virginia

    2010-01-01

    Infants' responses to typical and scrambled human body shapes were assessed in relation to the realism of the human body stimuli presented. In four separate experiments, infants were familiarized to typical human bodies and then shown a series of scrambled human bodies on the test. Looking behaviour was assessed in response to a range of different…

  2. 237Poverty and Human Capability Studies Poverty and Human

    E-print Network

    Dresden, Gregory

    237Poverty and Human Capability Studies Poverty and Human CaPability StudieS (Pov) Core Fa and Human Capability offers a cur- ricular and cocurricular program of study that enriches any major to establish a decent minimum of human development for all people. Students complet- ing designated

  3. Policy on Human Subjects Research Policy on Human Subjects

    E-print Network

    Sridhar, Srinivas

    Policy on Human Subjects Research 10/15/2014 Policy on Human Subjects Research I. Purpose and Scope ethical standards for the protection of human subjects, consistent with the principles of the Nuremberg Code and the Belmont Report. Accordingly, the University has established the Office of Human Subject

  4. College of Applied Human Sciences College of Applied Human Sciences

    E-print Network

    Stephens, Graeme L.

    Administration Health and Exercise Science Human Development and Family Studies Interior Design Nutrition Nutrition; Health and Exercise Science; Human Development and Family Studies; and Occupational TherapyCollege of Applied Human Sciences _______________ 2.6 Page 1 College of Applied Human Sciences

  5. Human genome diversity: What about the other human genome project?

    Microsoft Academic Search

    Henry T. Greely

    2001-01-01

    Although the Human Genome Project has been successful, the Human Genome Diversity Project, proposed in 1991, has so far failed to thrive. One of the main values in studying the human genome, however, will come from examining its variations and their effects. To do that in a systematic way, an active Human Genome Diversity Project, or something very similar, will

  6. The Human Genome From human genome to other

    E-print Network

    Linial, Michal

    The Human Genome Project From human genome to other genomes and to gene function June 2000 From genome to health Structural Genomics initiative #12;What is the Human Genome Project? · U.S. govt that arise from genome research #12;The Human Genome Project Project began in 1990 as a $3 billion, 15-year

  7. Developing Human Performance Measures

    SciTech Connect

    Jeffrey Joe; Bruce Hallbert; Larry Blackwood; Donald Dudehoeffer; Kent Hansen

    2006-05-01

    Through the reactor oversight process (ROP), the U.S. Nuclear Regulatory Commission (NRC) monitors the performance of utilities licensed to operate nuclear power plants. The process is designed to assure public health and safety by providing reasonable assurance that licensees are meeting the cornerstones of safety and designated crosscutting elements. The reactor inspection program, together with performance indicators (PIs), and enforcement activities form the basis for the NRC’s risk-informed, performance based regulatory framework. While human performance is a key component in the safe operation of nuclear power plants and is a designated cross-cutting element of the ROP, there is currently no direct inspection or performance indicator for assessing human performance. Rather, when human performance is identified as a substantive cross cutting element in any 1 of 3 categories (resources, organizational or personnel), it is then evaluated for common themes to determine if follow-up actions are warranted. However, variability in human performance occurs from day to day, across activities that vary in complexity, and workgroups, contributing to the uncertainty in the outcomes of performance. While some variability in human performance may be random, much of the variability may be attributed to factors that are not currently assessed. There is a need to identify and assess aspects of human performance that relate to plant safety and to develop measures that can be used to successfully assure licensee performance and indicate when additional investigation may be required. This paper presents research that establishes a technical basis for developing human performance measures. In particular, we discuss: 1) how historical data already gives some indication of connection between human performance and overall plant performance, 2) how industry led efforts to measure and model human performance and organizational factors could serve as a data source and basis for a framework, 3) how our use of modeling and simulation techniques could be used to develop and validate measures of human performance, and 4) what the possible outcomes are from this research as the modeling and simulation efforts generate results.

  8. Human behavior and human performance: Psychomotor demands

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The results of several experiments are presented in abstract form. These studies are critical for the interpretation and acceptance of flight based science to be conducted by the Behavior and Performance project. Some representative titles are as follow: External audio for IBM/PC compatible computers; A comparative assessment of psychomotor performance (target prediction by humans and macaques); Response path (a dependent measure for computer maze solving and other tasks); Behavioral asymmetries of psychomotor performance in Rhesus monkey (a dissociation between hand preference and skill); Testing primates with joystick based automated apparatus; and Environmental enrichment and performance assessment for ground or flight based research with primates;

  9. Meeting human needs

    NASA Technical Reports Server (NTRS)

    Nicogossian, Arnauld E.

    1992-01-01

    Manned space flight can be viewed as an interaction of three general elements: the human crewmember, spacecraft systems, and the environment. While the human crewmember is a crucial element in the system, certain physiological, psychological, environ- mental and spacecraft systems factors can compromise human performance in space. These factors include atmospheric pressure, physiology, uncertainties associated with space radiation, the potential for exposure to toxic materials in the closed environment, and spacecraft habitability. Health protection in space, for current and future missions, relies on a philosophy of risk reduction, which in the space program is achieved in four ways-through health maintenance, health care, design criteria, an selection and training. Emphasis is place upon prevention, through selection criteria and careful screening. Spacecraft health care systems must be absolutely reliable, and they will be automated and computerized to the maximum extent possible, but still designed with the human crewmember's capabilities in mind. The autonomy and technological sophistication of future missions will require a greater emphasis on high-level interaction between the human operator and automated systems, with effective allocation of tasks between humans and machines. Performance in space will include complex tasks during extravehicular activity (EVA) and on planetary surfaces, and knowledge of crewmembers' capability and limitations during such operations will be critical to mission success. Psychological support will become increasingly important on space missions, as crews spend long periods in remote and potentially hazardous environments. The success of future missions will depend on both individual psychological health and group cohesion and productivity, particularly as crew profiles become more heterogeneous. Thus, further human factors are needed in the area of small-group dynamics and performance.

  10. Spaceflight Human System Standards

    NASA Technical Reports Server (NTRS)

    Holubec, Keith; Tillman, Barry; Connolly, Jan

    2009-01-01

    NASA created a new approach for human system integration and human performance standards. NASA created two documents a standard and a reference handbook. The standard is titled NASA Space Flight Human-System Standard (SFHSS) and consists of two-volumes: Volume 1- Crew Health This volume covers standards needed to support astronaut health (medical care, nutrition, sleep, exercise, etc.) Volume 2 Human Factors, Habitability and Environmental Health This volume covers the standards for system design that will maintain astronaut performance (ie., environmental factors, design of facilities, layout of workstations, and lighting requirements). It includes classic human factors requirements. The new standards document is written in terms so that it is applicable to a broad range of present and future NASA systems. The document states that all new programs prepare system-specific requirements that will meet the general standards. For example, the new standard does not specify a design should accommodate specific percentiles of a defined population. Rather, NASA-STD-3001, Volume 2 states that all programs shall prepare program-specific requirements that define the user population and their size ranges. The design shall then accommodate the full size range of those users. The companion reference handbook, Human Integration Design Handbook (HIDH), was developed to capture the design consideration information from NASA-STD-3000, and adds spaceflight lessons learned, gaps in knowledge, example solutions, and suggests research to further mature specific disciplines. The HIDH serves two major purposes: HIDH is the reference document for writing human factors requirements for specific systems. HIDH contains design guidance information that helps insure that designers create systems which safely and effectively accommodate the capabilities and limitations of space flight crews.

  11. Human Modeling for Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  12. Human Modeling For Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  13. The Exploration of Mars by Humans: Why Mars? Why Humans?

    NASA Technical Reports Server (NTRS)

    Levine, Joel S.

    2011-01-01

    As we commemorate the 50th anniversary of Yuri Gagarin's historic flight in 1961, the first flight of a human in space, plans are underway for another historic human mission. Plans are being developed for a human mission to Mars. Once we reach Mars, the human species will become the first two-planet species. Both the Bush Administration (in 2004) and the Obama Administration (in 2010) proposed a human mission to Mars as a national goal of the United States.

  14. Human Rights: The Essential Reference.

    ERIC Educational Resources Information Center

    Devine, Carol; Hansen, Carol Rae; Wilde, Ralph; Bronkhorst, Daan; Moritz, Frederic A.; Rolle, Baptiste; Sherman, Rebecca; Southard, Jo Lynn; Wilkinson, Robert; Poole, Hilary, Ed.

    This reference work documents the history of human rights theory, explains each article of the Universal Declaration of Human Rights, explores the contemporary human rights movement, and examines the major human rights issues facing the world today. This book is the first to combine historical and contemporary perspectives on these critical…

  15. Making IBM's Computer, Watson, Human

    ERIC Educational Resources Information Center

    Rachlin, Howard

    2012-01-01

    This essay uses the recent victory of an IBM computer (Watson) in the TV game, "Jeopardy," to speculate on the abilities Watson would need, in addition to those it has, to be human. The essay's basic premise is that to be human is to behave as humans behave and to function in society as humans function. Alternatives to this premise are considered…

  16. Human bites - self-care

    MedlinePLUS

    A human bite can break, puncture, or tear the skin. Human bites that break the skin can be very ... Bites - human - self-care ... Human bites can occur in two ways: If someone bites you If your hand comes into contact ...

  17. Human evolution: taxonomy and paleobiology

    Microsoft Academic Search

    BERNARD WOOD; BRIAN G. RICHMOND

    2000-01-01

    This review begins by setting out the context and the scope of human evolution. Several classes of evidence, morphological, molecular, and genetic, support a particularly close relationship between modern humans and the species within the genus Pan, the chimpanzee. Thus human evolution is the study of the lineage, or clade, comprising species more closely related to modern humans than to

  18. Human values and natural systems

    Microsoft Academic Search

    Holmes Rolston III

    1988-01-01

    . Ecological valu~s contribute positively to human experiences but also seem to be there apart from humans. In an evolutionary ecosystem, the centtal goods of the biosys­ temic Earth were in place before humans arrived. Humans cash in on and spend what is naturally given. In many respects, though by no means all, the earthen setup is \\

  19. The Humanities at Triton College.

    ERIC Educational Resources Information Center

    Jacot, Robert E.; Prendergast, Nancy E.

    Designed to assist college personnel in assessing program needs, this report provides an overview of the humanities programs at Triton College. Part I focuses on curricular humanities programs, including discussions of the role and objectives of the School of Arts and Sciences; humanities courses offered in the school; special humanities…

  20. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  1. Human occupancy detection

    NASA Astrophysics Data System (ADS)

    Brown, David A.

    1994-10-01

    In the area of security and surveillance technologies, the problem of the arrival in Canada of illegal and undesirable ship and truck cargo loads is steadily increasing. As the volumes of cargo arrivals increase so do the Immigration and Customs problems related to the determination of the validity of those cargo contents. Of special concern to Immigration Control Authorities around the world is the emerging and increasing trend of illegal smuggling of human beings hidden inside of shipping containers. Beginning in 1992, Immigration Control Authorities in Canada observed an escalation of alien people smuggling through the use of cargo shipping containers arriving in the Port of Montreal. This paper will present to the audience the recently completed Immigration Canada Human Occupancy Detection project by explaining the design, development and testing of human occupancy detectors. The devices are designed to electronically detect the presence of persons hiding inside of shipping containers, without the requirement of opening the container doors. The human occupancy detection concepts are based upon the presence of carbon dioxide or other human waste characteristics commonly found inside of shipping containers.

  2. Human herpesvirus 6.

    PubMed Central

    Braun, D K; Dominguez, G; Pellett, P E

    1997-01-01

    Human herpesvirus 6 variant A (HHV-6A) and human herpesvirus 6 variant B (HHV-6B) are two closely related yet distinct viruses. These visuses belong to the Roseolovirus genus of the betaherpesvirus subfamily; they are most closely related to human herpesvirus 7 and then to human cytomegalovirus. Over 95% of people older than 2 years of age are seropositive for either or both HHV-6 variants, and current serologic methods are incapable of discriminating infection with one variant from infection with the other. HHV-6A has not been etiologically linked to any human disease, but such an association will probably be found soon. HHV-6B is the etiologic agent of the common childhood illness exanthem subitum (roseola infantum or sixth disease) and related febrile illnesses. These viruses are frequently active and associated with illness in immunocompromised patients and may play a role in the etiology of Hodgkin's disease and other malignancies. HHV-6 is a commensal inhabitant of brains; various neurologic manifestations, including convulsions and encephalitis, can occur during primary HHV-6 infection or in immunocompromised patients. HHV-6 and distribution in the central nervous system are altered in patients with multiple sclerosis; the significance of this is under investigation. PMID:9227865

  3. The Human Genome Program

    SciTech Connect

    Bell, G.I.

    1989-01-01

    Early in 1986, Charles DeLisi, then head of the Office of Health and Environmental Research at the Department of Energy (DOE) requested the Los Alamos National Laboratory (LANL) to organize a workshop charged with inquiring whether the state of technology and potential payoffs in biological knowledge and medical practice were such as to justify an organized program to map and sequence the human genome. The DOE's interest arose from its mission to assess the effects of radiation and other products of energy generation on human health in general and genetic material in particular. The workshop concluded that the technology was ripe, the benefits would be great, and a national program should be promptly initiated. Later committees, reporting to DOE, to the NIH, to the Office of Technology Assessment of the US Congress, and to the National Academy of Science have reviewed these issues more deliberately and come to the same conclusion. As a consequence, there has been established in the United States, a Human Genome Program, with funding largely from the NIH and the DOE, as indicated in Table 1. Moreover, the Program has attracted international interest, and Great Britain, France, Italy, and the Soviet Union, among other countries, have been reported to be starting human genome initiatives. Coordination of these programs, clearly in the interests of each, remains to be worked out, although an international Human Genome Organization (HUGO) is considering such coordination. 5 refs., 1 fig., 2 tabs.

  4. Digital Humanities Tool Box

    NSDL National Science Digital Library

    The Digital Humanities Tool Box, hosted on Scoop.It!, bills itself as a web site packed with â??Links, ideas, and tools for humanities instructors.â? And thatâ??s exactly what it is. Curated by a history professor at Arizona State University (web name: Stillwater Humanities), the site â??scoopsâ? resources from around the web. Recent gems include articles like â??Historyâ??s Futureâ? and â??A Brief History of the Hashtag, and Other Unusual Punctuation Marks,â? as well as infographics (for example, â??6 Ways Social Media Will Change in 2014â?) and blog entries (e.g. â??What Digitization Will Do for the Future of Museumsâ?).

  5. Human & Constitutional Rights

    NSDL National Science Digital Library

    The Arthur W. Diamond Law Library at Columbia Law School maintains this excellent resource for finding materials on human rights and constitutional rights. The metasite serves students, scholars, and practitioners as a portal to documents and Internet resources on international and domestic law related to human and constitutional rights. The information resources are divided into six sections: Country Reports, International Links, Regional Links, National Links, Documents, and Other Web Resources. Each section is clearly organized into neat lists or pop-up menus to ease navigation. Marylin Raisch -- the International, Comparative, and Foreign Law Librarian responsible for this metasite -- also provides a Hot Topics section, which posts information on current events related to human and constitutional rights.

  6. Scientists and Human Rights

    NASA Astrophysics Data System (ADS)

    Makdisi, Yousef

    2012-02-01

    The American Physical Society has a long history of involvement in defense of human rights. The Committee on International Freedom of Scientists was formed in the mid seventies as a subcommittee within the Panel On Public Affairs ``to deal with matters of an international nature that endangers the abilities of scientists to function as scientists'' and by 1980 it was established as an independent committee. In this presentation I will describe some aspects of the early history and the impetus that led to such an advocacy, the methods employed then and how they evolved to the present CIFS responsibility ``for monitoring concerns regarding human rights for scientists throughout the world''. I will also describe the current approach and some sample cases the committee has pursued recently, the interaction with other human rights organizations, and touch upon some venues through which the community can engage to help in this noble cause.

  7. Journal of Digital Humanities

    NSDL National Science Digital Library

    The Journal of Digital Humanities is a comprehensive, peer-reviewed, open access journal that features "the best scholarship, tools, and conversations produced by the digital humanities community." This endeavor was started by the Press Forward Project and its rigorous evaluation process ensures that interested parties will be exposed to a wide range of talent and subject matter. Arranged by trimester, recent issues of the journal have focused in on the ways digital humanities projects can be used to teach undergraduates about the world around them, while also highlighting the pedagogy involved with such endeavors. Visitors can search through the entire collection of back issues or they may also look through the list of contributors to get a sense of those involved with the project.

  8. North Carolina Humanities Council

    NSDL National Science Digital Library

    Created in 1972, the North Carolina Humanities Council is a statewide nonprofit and affiliate of the National Endowment for the Humanities that works to make the humanities "a cornerstone of public life." The Council's bright and well-designed website contains information about grant-making initiatives, upcoming events and talks, and publications as well as a gallery of images. First-time visitors may want to start by browsing through the latest issues of "North Carolina Conversations," found under Publications. One recent issue included a profile of downtown Greensboro, a short story by John York, and information on traveling folklife exhibits. The Programs area contains vibrant information on the Council's "Road Scholars" initiative, which brings speakers to audiences around the state. Also, this area contains the "Museum on Main Street," which provides information on the traveling exhibit jointly sponsored by the Council and the Smithsonian Institution Traveling Exhibition. The Publications area contains the Council's annual reports and its newsletter, "Crossroads"

  9. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

    An investigation of the spectrum of space teleoperation activities likely in the 1985 to 1995 decade focused on the resolution of critical human engineering issues and characterization of the technology effect on performance of remote human operators. The study began with the identification and documentation of a set of representative reference teleoperator tasks. For each task, technology, development, and design options, issues, and alternatives that bear on human operator performance were defined and categorized. A literature survey identified existing studies of man/machine issues. For each teleoperations category, an assessment was made of the state of knowledge on a scale from adequate to void. The tests, experiments, and analyses necessary to provide the missing elements of knowledge were then defined. A limited set of tests were actually performed, including operator selection, baseline task definition, control mode study, lighting study, camera study, and preliminary time delay study.

  10. The Human Nature Review

    NSDL National Science Digital Library

    While attempting to cover one area of scholarly discipline in a Web site may be a formidable task, the editors of the Human Nature Review are concerned with any substantive scholarship or research dealing with human nature in its entirety. As the Web site notes: "Our goal is to bring into communication the variety of approaches to the understanding of human nature which have a regrettable tendency to be less in touch with one another than they might." The site is edited by Dr. Ian Pitchford of the Creighton University School of Medicine and Professor Robert M. Young. Prominent features of the site include an online dictionary of mental health, a daily review (sent as an email, if users so desire) of updates on ongoing scholarship in the fields of psychology and psychotherapy, and a number of complete online texts. Finally, the site also houses hundreds of book reviews, contributed by scholars from a diverse set of fields, on works of topical importance.

  11. The human toxome project.

    PubMed

    Bouhifd, Mounir; Andersen, Melvin E; Baghdikian, Christina; Boekelheide, Kim; Crofton, Kevin M; Fornace, Albert J; Kleensang, Andre; Li, Henghong; Livi, Carolina; Maertens, Alexandra; McMullen, Patrick D; Rosenberg, Michael; Thomas, Russell; Vantangoli, Marguerite; Yager, James D; Zhao, Liang; Hartung, Thomas

    2015-01-01

    The Human Toxome Project, funded as an NIH Transformative Research grant 2011-2016, is focused on developing the concepts and the means for deducing, validating and sharing molecular pathways of toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF-7 human breast cancer cells are being phenotyped by transcriptomics and mass-spectroscopy-based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A number of challenges for quality and standardization of cell systems, omics technologies and bioinformatics are being addressed. In parallel, concepts for annotation, validation and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge-base, could become a point of reference for toxicological research and regulatory test strategies. PMID:25742299

  12. Human Embryology Animations

    NSDL National Science Digital Library

    O'Loughlin, Valerie

    2012-03-02

    For students of human development, the Human Embryology Animations site is a worthy resource. Created by Dr. Valerie O'Loughlin at Indiana University, the goal of this site is to help students "better understand the complex processes that must occur in embryologic development." The animations are divided into five thematic sections, including General Embryology, Development of the Limbs, and Urinary and Reproductive Embryology. Each animation lasts anywhere from 20 seconds to 8 minutes, and they cover heart tube folding, septum development, postnatal circulation, and 30 or so other processes. The site is designed for students and members of the general public with a basic understanding of human biology, and the animations are well-planned and worth a look. Additionally, they could be used for students reviewing materials for a course like AP Biology.

  13. Uncovering the Human Methyltransferasome*

    PubMed Central

    Petrossian, Tanya C.; Clarke, Steven G.

    2011-01-01

    We present a comprehensive analysis of the human methyltransferasome. Primary sequences, predicted secondary structures, and solved crystal structures of known methyltransferases were analyzed by hidden Markov models, Fisher-based statistical matrices, and fold recognition prediction-based threading algorithms to create a model, or profile, of each methyltransferase superfamily. These profiles were used to scan the human proteome database and detect novel methyltransferases. 208 proteins in the human genome are now identified as known or putative methyltransferases, including 38 proteins that were not annotated previously. To date, 30% of these proteins have been linked to disease states. Possible substrates of methylation for all of the SET domain and SPOUT methyltransferases as well as 100 of the 131 seven-?-strand methyltransferases were surmised from sequence similarity clusters based on alignments of the substrate-specific domains. PMID:20930037

  14. Human Ageing Genomic Resources

    NSDL National Science Digital Library

    The Human Ageing Genomic Resources (HAGR)â??currently led by Dr. João Pedro de Magalhães at the Harvard Medical Schoolâ??is "a collection of databases and tools designed to help researchers understand the genetics of human ageing.â? Two major searchable resources offered in HAGR are AnAge, a curated animal ageing database with more than 2,000 species; and GenAge, â??a curated database of genes related to human ageing.â? Site visitors are encouraged to download the HAGR software, Ageing Resources Computational Tools, which â??is a toolkit of Perl modules based on the Bioperl package aimed a comparative genomics.â? Site users will also appreciate the solid list of related links organized into the following categories: Major Databases, Gerontology Databases, Computer Science, Comparative Biology, and Computational Biology.

  15. Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  16. Humanities on the Road

    NSDL National Science Digital Library

    The goal of the Pennsylvania Humanities Council is to encourage lifelong learning, and one way they accomplish this goal is by sponsoring the Humanities on the Road. The show is an "arts and culture-themed television series showcas[ing] humanities presentations at cultural sites across Pennsylvania." The accompanying website provides visitors access to the episodes of the series, along with text about the content of each show. Visitors should check out the episode "May I Have the Pleasure of This Dance?", which was filmed at the Scranton Cultural Center at the Masonic Temple. A couple dances their way through history through waltzes, tangos, ragtime, and more. The "Behind the Scenes" tab near the top of the page offers visitors a glimpse into the world of the crew of the show, including interviews with the host, the series producer, the production assistant, and others.

  17. Antimutagenic effects in humans

    SciTech Connect

    Mendelsohn, M.L.

    1991-06-10

    The application of antimutagenicity studies to human somatic mutation is discussed, with emphasis on the potential for future studies. Five assay-gene combinations are now available for measuring human somatic mutation in lymphocytes and erythrocytes. Results with these combinations have defined the human background levels, and show clear responses of mutant frequency to a variety of mutagens. The testing of antimutagenic effects of background frequencies is feasible, but has not yet been done. The major uncertainty in such studies is the unknown age of mutant cells in the background, since only the newly forming mutants are potentially susceptible to most antimutagenic treatments. Intervention studies in the face of active mutagenicity and the use of other genotoxicity endpoints, such as chromosome aberrations, micronuclei and DNA adducts, are considered briefly. 42 refs.

  18. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    ERIC Educational Resources Information Center

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  19. Telocytes in human epicardium

    PubMed Central

    Popescu, L M; Manole, C G; Gherghiceanu, M; Ardelean, A; Nicolescu, M I; Hinescu, M E; Kostin, S

    2010-01-01

    Abstract The existence of the epicardial telocytes was previously documented by immunohistochemistry (IHC) or immunofluorescence. We have also demonstrated recently that telocytes are present in mice epicardium, within the cardiac stem-cell niches, and, possibly, they are acting as nurse cells for the cardiomyocyte progenitors. The rationale of this study was to show that telocytes do exist in human (sub)epicardium, too. Human autopsy hearts from 10 adults and 15 foetuses were used for conventional IHC for c-kit/CD117, CD34, vimentin, S-100, ?, Neurokinin 1, as well as using laser confocal microscopy. Tissue samples obtained by surgical biopsies from 10 adults were studied by digital transmission electron microscopy (TEM). Double immunolabelling for c-kit/CD34 and, for c-kit/vimentin suggests that in human beings, epicardial telocytes share similar immunophenotype features with myocardial telocytes. The presence of the telocytes in human epicardium is shown by TEM. Epicardial telocytes, like any of the telocytes are defined by telopodes, their cell prolongations, which are very long (several tens of ?m), very thin (0.1–0.2 ?m, below the resolving power of light microscopy) and with moniliform configuration. The interconnected epicardial telocytes create a 3D cellular network, connected with the 3D network of myocardial telocytes. TEM documented that telocytes release shed microvesicles or exocytotic multivesicular bodies in the intercellular space. The human epicardial telocytes have similar phenotype (TEM and IHC) with telocytes located among human working cardiomyocyte. It remains to be established the role(s) of telocytes in cardiac renewing/repair/regeneration processes, and also the pathological aspects induced by their ‘functional inhibition’, or by their variation in number. We consider telocytes as a real candidate for future developments of autologous cell-based therapy in heart diseases. PMID:20629996

  20. NAMPT and NAPRT1: novel polymorphisms and distribution of variants between normal tissues and tumor samples

    PubMed Central

    Duarte-Pereira, Sara; Silva, Sarah S.; Azevedo, Luísa; Castro, Luísa; Amorim, António; Silva, Raquel M.

    2014-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase domain containing 1 (NAPRT1) are the main human NAD salvage enzymes. NAD regulates energy metabolism and cell signaling, and the enzymes that control NAD availability are linked to pathologies such as cancer and neurodegeneration. Here, we have screened normal and tumor samples from different tissues and populations of origin for mutations in human NAMPT and NAPRT1, and evaluated their potential pathogenicity. We have identified several novel polymorphisms and showed that NAPRT1 has a greater genetic diversity than NAMPT, where any alteration can have a greater functional impact. Some variants presented different frequencies between normal and tumor samples that were most likely related to their population of origin. The novel mutations described that affect protein structure or expression levels can be functionally relevant and should be considered in a disease context. Particularly, mutations that decrease NAPRT1 expression can predict the usefulness of Nicotinic Acid in tumor treatments with NAMPT inhibitors. PMID:25201160

  1. Augmented Human Engineering: A Theoretical and Experimental

    E-print Network

    Paris-Sud XI, Université de

    . Thus, augmented human design has to integrate human factors - anatomy, neurophysiology, behaviour12 Augmented Human Engineering: A Theoretical and Experimental Approach to Human Systems. Introduction This chapter focuses on one of the main issues for augmented human engineering: integrating

  2. Human Mitochondrial Protein Database

    NSDL National Science Digital Library

    The Human Mitochondrial Protein Database (HMPDb) conveniently consolidates information from a number of other databases, including GenBank, Online Mendelian Inheritance in Man, and the Human Mitochondrial Genome Database. HMPDb "is intended as a tool not only to aid in studying the mitochondrion but in studying the associated diseases" as well. Features include a general database search, a graphical tool for visualizing the mitochondrial DNA sequences, and 3D structures for mitochondrial proteins. Users are welcome to contact the National Institute of Standards and Technology with corrections or other information relating to the database.

  3. Sanitation and Human Health

    NSDL National Science Digital Library

    Science Netlinks

    2000-12-06

    The purpose of this Science NetLinks lesson is to develop an understanding of the impact of improved sanitation on human health. In this lesson, students learn something about the ways that sanitation technology has helped people by examining the history of sanitation in the context of disease outbreaks and comparing the quality of life in those times to that of today. By the end of this lesson, students should recognize that advances in health and human life expectancy have resulted in large part because of technologies that we now take for granted, such as modern waste-disposal, sanitary food handling, and refrigeration.

  4. Microsporidia and human infections.

    PubMed Central

    Shadduck, J A; Greeley, E

    1989-01-01

    Protozoa of the phylum Microspora are obligate intracellular pathogens that are being detected with increasing frequency in humans, especially in patients with acquired immunodeficiency syndrome. Organisms from four genera have been reported to date, and serological data suggest the occurrence of latent infections. Sources of human infections are not known, but microsporidia are widespread in lower vertebrates and invertebrates. There is no known treatment. Study of the disease in mammals suggests that infection often will be clinically silent, that intact T-cell-mediated host defenses are required for resistance, and that serious clinical disease may occur under circumstances in which extensive parasite replication can occur. Images PMID:2650860

  5. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the ? -? -? globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  6. Human MSH2 protein

    DOEpatents

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  7. Mapping human epigenomes.

    PubMed

    Rivera, Chloe M; Ren, Bing

    2013-09-26

    As the second dimension to the genome, the epigenome contains key information specific to every type of cells. Thousands of human epigenome maps have been produced in recent years thanks to rapid development of high throughput epigenome mapping technologies. In this review, we discuss the current epigenome mapping toolkit and utilities of epigenome maps. We focus particularly on mapping of DNA methylation, chromatin modification state, and chromatin structures, and emphasize the use of epigenome maps to delineate human gene regulatory sequences and developmental programs. We also provide a perspective on the progress of the epigenomics field and challenges ahead. PMID:24074860

  8. Human MSH2 protein

    DOEpatents

    de la Chapelle, Albert (Helsingfors, FI); Vogelstein, Bert (Baltimore, MD); Kinzler, Kenneth W. (Baltimore, MD)

    1997-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  9. Mapping Human Epigenomes

    PubMed Central

    Rivera, Chloe M.; Ren, Bing

    2013-01-01

    As the second dimension to the genome, the epigenome contains key information specific to every type of cells. Thousands of human epigenome maps have been produced in recent years thanks to rapid development of high throughput epigenome mapping technologies. In this review, we discuss the current epigenome mapping toolkit and utilities of epigenome maps. We focus particularly on mapping of DNA methylation, chromatin modification state and chromatin structures, and emphasize the use of epigenome maps to delineate human gene regulatory sequences and developmental programs. We also provide a perspective on the progress of the epigenomics field and challenges ahead. PMID:24074860

  10. Human Sciences Research Council

    NSDL National Science Digital Library

    The Human Sciences Research Council provides news and research in South African social sciences, including economics, social analysis, education, and governance. The site posts weekly media releases on contemporary topics; recent working papers; and "published findings" on such topics as Children's Rights in South Africa, Human Rights and Democratization, and pending social legislation. (A search engine is provided for these materials, but wasn't accessible when we visited.) The site also gives some annotated links to prime databases for further research on South Africa. Note: the site's book-length publications generally must be ordered online.

  11. Human Development Index Data

    NSDL National Science Digital Library

    United Nations

    This data set traces the varying patterns of national progress in recent decades, documenting impressive long-term Human Development Index (HDI) gains even in most low-income countries. The data set also includes three innovative new measurements: the Inequality-adjusted Human Development Index (IHDI), the Gender Inequality Index (GII) and the Multidimensional Poverty Index (MPI). The data set is available in both CSV and SDMX file formats and contains more than 100 indicators that measure quality of life for all UN member states.

  12. American Humane Association

    NSDL National Science Digital Library

    Most people know of the American Humane Association (AHA) from the "No animals were harmed" disclaimer at the end of a movie or television show, but the AHA has been protecting children, as well as animals, since 1877. According to their website, they aim to end the abuse and neglect of children and animals, and are at the forefront of "understanding the human-animal interaction and its role in society." Users can learn facts about child abuse and neglect, research policy and government affairs and more. The "Act Now" link displays current child advocacy campaigns underway.

  13. Ayahuasca and human destiny.

    PubMed

    McKenna, Dennis J

    2005-06-01

    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time? PMID:16149337

  14. On human health.

    PubMed

    van Spijk, Piet

    2015-05-01

    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health. PMID:25300821

  15. [Controversies about human cloning].

    PubMed

    Ziga, Jusuf

    2006-01-01

    Human cloning is one of the greatest scientific and research challenges that human kind faced so far. As much as we have reasons for excitement in front of achievements of the genetic engineering, also are great the fears about it. There is inevitable question: is the man aware where can cloning as an attack on a "natural laws for the life reproduction" can lead, or to say its impact on evolution diversities within kind that we belongs to. In this paper we have focus on finding the answer on the last question, with application of a multidisciplinary approach, which means not only scientific, but also ethical, as well as theology. PMID:16719236

  16. Cardiovascular Deconditioning in Humans: Human Studies Core

    NASA Technical Reports Server (NTRS)

    Williams, Gordon

    1999-01-01

    Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

  17. Movement Coordination in Applied Human-Human and Human-Robot Interaction

    Microsoft Academic Search

    Anna Schubö; Cordula Vesper; Mathey Wiesbeck; Sonja Stork

    2007-01-01

    The present paper describes a scenario for examining mechanisms of movement coordination in humans and robots. It is assumed\\u000a that coordination can best be achieved when behavioral rules that shape movement execution in humans are also considered for\\u000a human-robot interaction. Investigating and describing human-human interaction in terms of goal-oriented movement coordination\\u000a is considered an important and necessary step for designing

  18. Altruistic punishment in humans

    Microsoft Academic Search

    Ernst Fehr; Simon Gächter

    2002-01-01

    Human cooperation is an evolutionary puzzle. Unlike other creatures, people frequently cooperate with genetically unrelated strangers, often in large groups, with people they will never meet again, and when reputation gains are small or absent. These patterns of cooperation cannot be explained by the nepotistic motives associated with the evolutionary theory of kin selection and the selfish motives associated with

  19. Human pythiosis in Thailand

    Microsoft Academic Search

    P. Imwidthaya

    1994-01-01

    Pythium insidiosum is a protoctista and causes diseases in plants and animals. In Thailand it can cause a unique human infection of three types. The first type is a subcutaneous lesion in thalassaemic patients, with the pathological findings of a granulomatous reaction, diffuse infiltration, and oedema of the vessel walls. The patients responded to a saturated solution of potassium iodide.

  20. Human Social Genomics

    PubMed Central

    Cole, Steven W.

    2014-01-01

    A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA) characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural “social signal transduction” pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving. PMID:25166010

  1. Human Rights in Education

    E-print Network

    Ellis, Randy

    in the 1960s, is evident in the talk about rights of varied groups, such as women, aboriginal populations1 Human Rights in Education European View on Childhood and Education . .3 Children's Rights in Competitive Sport . . . . . . . . .4 Equality Rights of the Child . . . . . . . . . . . . . . .6 Resources

  2. Whale and Human Ears

    NSDL National Science Digital Library

    2003-09-26

    What do whale ears look like? You might be surprised! These two versions of this diagram -- one with the anatomical parts labeled and one that students can label themselves -- compare the anatomy of a whale ear to that of a human ear. From Marine Biology: Environment, Diversity, and Ecology by David Lerman

  3. Animating human athletics

    Microsoft Academic Search

    Jessica K. Hodgins; Wayne L. Wooten; David C. Brogan; James F. O'Brien

    1995-01-01

    This paper describes algorithms for the animation of men and women performing three dynamic athletic behaviors: running, bicycling, and vaulting. We animate these behaviors using control algorithms that cause a physically realistic model to perform the desired maneuver. For example, control algorithms allow the simulated humans to maintain balance while moving their arms, to run or bicycle at a variety

  4. What Predicts Human Trafficking?

    Microsoft Academic Search

    Kevin Bales

    2007-01-01

    If the international community has achieved agreement on the definition of human trafficking, we still have only a partial understanding of what drives it. We know that poverty and vulnerability represent ‘push?factors’ and that employment opportunity presents an important ‘pull?factor.’ But which of these factors is the most important? The regression analysis of 76 variables undertaken here confirms that corruption,

  5. Human Memory: The Basics

    ERIC Educational Resources Information Center

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  6. Fighting for Human Rights

    ERIC Educational Resources Information Center

    Ong, Bao

    2011-01-01

    Speak Truth To Power consists of 17 teacher-developed lessons based on the stories of rights advocates from all over the world. The lessons were created for sixth-through 12th-grade students, and have come to New York schools thanks to the Robert F. Kennedy Center for Justice and Human Rights and the New York State United Teachers union. Speak…

  7. Therapeutic Human Papillomavirus Vaccination

    Microsoft Academic Search

    Andreas E. Albers; Andreas M. Kaufmann

    2009-01-01

    Despite impressive progress in prevention and therapy of premalignant and malignant dysplasia the worldwide burden of cancer is relatively unchanged. Supplementation of the therapeutic arsenal by immunotherapeutic methods would have the potential to make a significant impact. Dysplastic lesions and cancer of the cervix show strong association with human papillomaviruses (HPV), as do tumours of other mucosal epithelia like squamous

  8. Study Abroad in Humanities

    E-print Network

    Heller, Barbara

    Study Abroad in Humanities Studying abroad is increasingly important for social science majors gained are critical to the companies' success. Why should I go abroad? Studying abroad is an opportunity your studies and career. Some of the potential benefits of going abroad include: Experience another

  9. Human Resources Management & SPHR

    E-print Network

    Garfunkel, Eric

    knowledge of essen al management skills ranging from Strategic Management to Nego a on. Leadership Skills managers who are required to be familiar with HR skills and laws. Self-paced Executive Education execedHuman Resources Management & SPHR® Re-Certification Associate Certificates Program Descrip

  10. Human Resources Maximization.

    ERIC Educational Resources Information Center

    Grabb, Larry E.

    1994-01-01

    Discusses human resources maximization as a means for expanding employee selection criteria to include applicants' strengths and potential for growth, not just their history, then working to develop employees potential. Testing learning style as a means for recognizing potential and the relationship between testing and training are discussed. (KRN)

  11. Human Ecology: Curriculum Review.

    ERIC Educational Resources Information Center

    Bybee, Rodger W.

    1984-01-01

    Describes nine commercially available programs which represent one aspect or a portion of the human ecology theme. Other information supplied for each program includes: program objectives; methods of instruction; specific subjects, grade, and ability levels; materials produced and purchasable; program implementation; teacher preparation; program…

  12. Neurobiology and the Humanities

    PubMed Central

    Zeki, Semir

    2014-01-01

    Can the arts and humanities contribute significantly to the study of the brain? Similar brain processes are involved in humanistic and scientific inference, and in this essay, I argue that conclusions reached by one are relevant to the other. PMID:25277451

  13. Humanizing the Workplace.

    ERIC Educational Resources Information Center

    Fairfield, Roy P., Ed.

    A series of essays discussing ideas about humanizing work are presented in the document. Three major sections divide the essays, and each includes a preface with comments suggesting the central focus and questions with which the authors are concerned. The first section deals with the history, philosophy, and issues related to work and contains…

  14. Learning to Be Human

    ERIC Educational Resources Information Center

    Macmurray, John

    2012-01-01

    This article presents "Learning to be Human", which John Macmurray delivered on 5 May 1958 as the annual public lecture at Moray House College of Education, now part of Edinburgh University. The key themes of the paper are ones to which Macmurray returned again and again in both his educational and his philosophical writing for over 40 years and…

  15. The human circadian metabolome

    PubMed Central

    Dallmann, Robert; Viola, Antoine U.; Tarokh, Leila; Cajochen, Christian; Brown, Steven A.

    2012-01-01

    The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest–activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ?15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure. PMID:22308371

  16. Human Learning and Memory

    ERIC Educational Resources Information Center

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  17. Medicine and the Humanities.

    ERIC Educational Resources Information Center

    Pabst, Diana

    1992-01-01

    Discusses a Pennsylvania State University seminar program designed to help medical professionals explore aspects of medical treatment through readings in the humanities. Argues that the program is broader in vision and scope that other medical ethics courses. Suggests that the effort can refresh and deepen doctors' work with patients. (SG)

  18. Human Development Student Modules.

    ERIC Educational Resources Information Center

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This set of 61 student learning modules deals with various topics pertaining to human development. The modules, which are designed for use in performance-based vocational education programs, each contain the following components: an introduction for the student, a performance objective, a variety of learning activities, content information, a…

  19. Trends in Human Factors

    Microsoft Academic Search

    Julien M. Christensen

    1958-01-01

    An attempt is made to define the metamorphosis of the human factors area since World War II. While excellent work has been accomplished on problems relating to the detailed design of systems components, there is a significant lack of information relating to the gross problems of systems design. The need for research in this important area is emphasized.A plea is

  20. Humans in space

    Microsoft Academic Search

    Ronald J. White; Maurice Averner

    2001-01-01

    Many successful space missions over the past 40 years have highlighted the advantages and necessity of humans in the exploration of space. But as space travel becomes ever more feasible in the twenty-first century, the health and safety of future space explorers will be paramount. In particular, understanding the risks posed by exposure to radiation and extended weightlessness will be

  1. Human chromosome 8.

    PubMed Central

    Wood, S

    1988-01-01

    The role of human chromosome 8 in genetic disease together with the current status of the genetic linkage map for this chromosome is reviewed. Both hereditary genetic disease attributed to mutant alleles at gene loci on chromosome 8 and neoplastic disease owing to somatic mutation, particularly chromosomal translocations, are discussed. PMID:3070042

  2. Humanized Youth Work

    ERIC Educational Resources Information Center

    Brokenleg, Martin

    2012-01-01

    The author reflects on the history of the Circle of Courage model in creating resilient children in a world where virtually all young people can be considered to be at risk. The author stresses that those people in the Reclaiming Youth movement are in the business of humanizing youth work and childcare. They continue to call adults back to the…

  3. Assemble the Human Heart

    NSDL National Science Digital Library

    COSI

    2000-01-01

    In this online activity about anatomy, learners will drag and drop pieces of the heart into their proper positions and explore what function each part of the heart has. This activity is part of a rather extensive collection of activities and information surrounding the wonder of the human heart.

  4. Human Specimen Resources | Resources

    Cancer.gov

    The Pathology Investigation and Resources Branch support programs that collect and distribute human biospecimens programs through grant funding. These programs make high-quality tissue and associated data available to the research community. Listed below is a description of current PIRB supported programs.

  5. Interacting with human physiology

    Microsoft Academic Search

    Ioannis Pavlidis; Jonathan Dowdall; Nanfei Sun; Colin Puri; Jin Fei; Marc Garbey

    2007-01-01

    We propose a novel system that incorporates physiological monitoring as part of the human–computer interface. The sensing element is a thermal camera that is employed as a computer peripheral. Through bioheat modeling of facial imagery almost the full range of vital signs can be extracted, including localize blood flow, cardiac pulse, and breath rate. This physiological information can then be

  6. Human performance measuring device

    NASA Technical Reports Server (NTRS)

    Michael, J.; Scow, J.

    1970-01-01

    Complex coordinator, consisting of operator control console, recorder, subject display panel, and limb controls, measures human performance by testing perceptual and motor skills. Device measures psychophysiological functions in drug and environmental studies, and is applicable to early detection of psychophysiological body changes.

  7. Food Affects Human Behavior.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

  8. RVF Appraising Human Vulnerability

    E-print Network

    McCarl, Bruce A.

    Hospitalization days Link to size of animal outbreak Endemic vs one time? #12;So What Do we need Can we link severity to animal outbreak size? human = f(animal size, rel pop density) #12; Economics Texas A&M University Presented at RVF Expert Consultation Washington, D.C. Dec 16, 2009 #12

  9. Marketing Human Resource Development.

    ERIC Educational Resources Information Center

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  10. Solving the human predicament

    Microsoft Academic Search

    Paul R. Ehrlich; Anne H. Ehrlich

    2012-01-01

    The authors offer an ecological frame of reference for political action to change the economic and social trends now deepening the human predicament: overpopulation and continuing population growth, overconsumption by rich societies, resource depletion, environmental degradation, and inequitable distribution of wealth within and between societies. Certain points often overlooked include: the demographic contribution to environmental deterioration; climate disruption, global toxification,

  11. Potatoes and Human Health

    Microsoft Academic Search

    Mary Ellen Camire; Stan Kubow; Danielle J. Donnelly

    2009-01-01

    The potato (Solanum tuberosum L.) tuber follows only rice and wheat in world importance as a food crop for human consumption. Cultivated potatoes have spread from the Andes of South America where they originated to 160 countries around the world. Consumption of fresh potatoes has declined while processed products have increased in popularity. As the potato becomes a staple in

  12. Biotechnologies and Human Dignity

    ERIC Educational Resources Information Center

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  13. Futures of Human Communication.

    ERIC Educational Resources Information Center

    Harms, L. S.

    There are several research areas basic to the long-range future of human communications. Telecommunication and transportation offer the possiblity of two worldwide communications networks whose interrelationships need to be explored in terms of the needs of the individual, the community, and the world at large. Expanding possibilities of…

  14. Lessons in Human Relations.

    ERIC Educational Resources Information Center

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  15. Rise of human intelligence

    Microsoft Academic Search

    Fernand Gobet; Guillermo Campitelli; Andrew J Waters

    2002-01-01

    Based upon the evidence that the best chess players in the world are becoming increasingly represented by relatively young individuals, Howard [Intelligence 27 (1999) 235–250.] claimed that human intelligence is rising over generations. We suggest that this explanation has several difficulties and show that alternative explanations relating to changes in the chess environment, including increased access to chess knowledge, offer

  16. HUMANITIES & SOCIAL SCIENCES

    E-print Network

    Yang, Eui-Hyeok

    and culture have changed and in- fluenced our world throughout the course of history. The humanities campus in the vibrant city of Hoboken, just across the river from the exciting intellectual and cultural opportu- nities offered by New York City. THE STEVENS ADVANTAGE: CLOSE-KNIT COMMUNITY As a student

  17. Genetic Modifications in Humans

    Microsoft Academic Search

    Erin McHale

    In the history of mankind, various media sources have produced predictions about scientific knowledge in future societies. Entertainment sources such as Aldous Huxley's novel, Brave New World, or Ridley Scott's movie, Bladerunner, have been used to reflect the various futuristic viewpoints on human genetics and their place in society. Only in the past decade have advances in biotechnology made these

  18. Early Human Predation

    Microsoft Academic Search

    Richard Potts

    \\u000a From a phylogenetic perspective, human predatory behavior is an isolated phenomenon in which the propensity to capture and\\u000a digest food from large vertebrate prey evolved in a minor clade of primates. From an ecological perspective, this phenomenon\\u000a has had enormous repercussions for the present structure of terrestrial food webs and animal biological diversity.

  19. On Human Intelligence

    E-print Network

    M. A. Anusuya; S. K. Katti

    Abstract — This paper presents some detailed discussions regarding the human natural intelligence, along with various types of intelligences. The authors have also given some important factors on which the intelligence depends. Therefore the authors strongly feel that this information given in this paper may be useful to the researchers who have been working in the area of Artificial Intelligence.

  20. Communication Human Relations

    E-print Network

    Jiang, Huiqiang

    .upb.pitt.edu/career.aspx Inequalities and Social Differences (2 courses) SOC 0201 Sociology of Gender SOC 0207 Racial and Ethnic Groups, social change, and the social causes and consequences of human behavior. Sociologists pay special and to become more sensitive to behavioral and value difference among people. Sociology majors at Pitt

  1. Humans as Lie Detectors.

    ERIC Educational Resources Information Center

    DePaulo, Bella; And Others

    1980-01-01

    Discusses several studies of whether and how well humans can detect lies. Examines the accuracy of such persons as well as the process of how they actually detect lies, how they think they detect lies, and whether the actual and perceived processes of lie detection correspond to one another. (JMF)

  2. Human Security Report Project

    NSDL National Science Digital Library

    The Human Security Report Project (HSRP) is based at Simon Fraser University in Canada, and it "conducts research on global and regional trends in political violence, their causes and consequences and presents its findings in a manner that is accessible to the policy and research communities, the media, educators and the interested public." The "About" section states that the e-resources it provides through its website has effectively changed the way human security issues are understood and managed. The "Publications" link on the left hand side menu provides access to the "Human Security Brief" for 2005-2007, as well as to "Articles", "Books", "Book Chapters", "Workshop Reports" and "Opinion Pieces". The categories of data used in the HSRP are fleshed out in the "Data Resources" link on the left hand side of the page. The categories of data used are "Armed Conflict", "Deadly Assault on Civilians", "Terrorism", and "Other Human Security Indicators". The nine "Research Initiatives" of the HSRP can be accessed on the right hand side menu.

  3. The Humanization of Education.

    ERIC Educational Resources Information Center

    Nechaev, N.; Usov, V.

    1991-01-01

    Warns against a tendency to command Soviet educational reform from above without thought of practical results. Criticizes proceeding before priorities have been set or put into practice, and ignoring the need for a vehicle of reform, material, and labor resources. Urges the humanization of architectural education through study of art, the…

  4. Communicating with Virtual Humans.

    ERIC Educational Resources Information Center

    Thalmann, Nadia Magnenat

    The face is a small part of a human, but it plays an essential role in communication. An open hybrid system for facial animation is presented. It encapsulates a considerable amount of information regarding facial models, movements, expressions, emotions, and speech. The complex description of facial animation can be handled better by assigning…

  5. Biomedical Ethics & Medical Humanities

    E-print Network

    Ford, James

    sciences (including anthropology and sociology). Here are examples of topics within BEMH: the impact of medical and technologic advances (such as genomics, stem cell research, etc); neuroethics; history, scholarly work and research; bioethics and medical humanities meetings; and elective courses. The minimum

  6. HUMAN GENETICS Individualgenomesdiversify

    E-print Network

    Zhang, Xin

    HUMAN GENETICS Individualgenomesdiversify Samuel Levy and Robert L. Strausberg The link between a person's genetic ancestry and the traits -- including disease risk -- that he or she exhibits remains. The rapid progress in genetic screening assays and DNA sequen- cing techniques promises to increase our

  7. Humanism: Tough or Tender?

    ERIC Educational Resources Information Center

    Cordell, Franklin D.; Luna, F. C.

    1978-01-01

    Describes the minimum conditions for creating the humanistic school. Humanism is based on principles that fall into three basic categories: a set of beliefs about self and the nature of social reality, a set of skills to be learned by teachers, administrators, and pupils, and a set of necessary conditions in the social system. (Author/RK)

  8. Human Values in Management

    Microsoft Academic Search

    R. K. Dasgupta

    1997-01-01

    The essay begins by the author's recollections of his younger days when people were seldom worried about moral decline in society. Today, however, it has become a real concern. Literature, philosophy, spiritual works are all essentially a celebration of human values. The paper examines the issue of scale of graded values as against that of absolutist universal values. A scrutiny

  9. The Human Genome Project

    Microsoft Academic Search

    Maynard V. Olson

    1993-01-01

    The Human Genome Project in the United States is now well underway. Its programmatic direction was largely set by a National Research Council report issued in 1988. The broad framework supplied by this report has survived almost unchanged despite an upheaval in the technology of genome analysis. This upheaval has primarily affected physical and genetic mapping, the two dominant activities

  10. Immunogenetics Human immunogenetics

    E-print Network

    Alper, Chester A.

    Opinion in Immunology 2004, 16:623­625 This review comes from a themed issue on Immunogenetics Edited is the cellular immunology and genetics of the human nonresponse to hepatitis B vaccine. This interest has is a relatively young and expanding area of biomedicine. It embraces the conjunction of genetics and immunology

  11. On Cloning Human Beings

    Microsoft Academic Search

    Inmaculada de Melo-Martín

    2002-01-01

    The purpose of this paper is to show that arguments for and against cloning fail to make their case because of one or both of the following reasons: 1) they take for granted customary beliefs and assumptions that are far from being unquestionable; 2) they tend to ignore the context in which human cloning is developed. I will analyze some

  12. Human Movement and Preference.

    ERIC Educational Resources Information Center

    Bechtel, Robert B.

    Why and how architecture and interior design can stimulate exploratory locomotion is discussed in terms of research and testing into human response. Two kinds of locomotion are defined, exploratory and habitual, with regard to locomotion and behavior responses to the architectural environment. Measuring responses with a hodometer is outlined with…

  13. Human Papilloma Virus Infections

    PubMed Central

    Wright, V. Cecil

    1989-01-01

    Genital warts are believed to be caused by human papilloma viruses and to be sexually transmitted. The viruses are classified by DNA types, which appear to cause different types of disease. The choice of treatment, and usually its success rate, vary according to the type of disease and its location. PMID:21248973

  14. Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera frame of reference. The first study investigated the effects of inclusion and exclusion of the robot chassis along with superimposing a simple arrow overlay onto the video feed of operator task performance during teleoperation of a mobile robot in a driving task. In this study, the front half of the robot chassis was made visible through the use of three cameras, two side-facing and one forward-facing. The purpose of the second study was to compare operator performance when teleoperating a robot from an egocentric-only and combined (egocentric plus exocentric camera) view. Camera view parameters that are found to be beneficial in these laboratory experiments can be implemented on NASA rovers and tested in a real-world driving and navigation scenario on-site at the Johnson Space Center.

  15. Sequential analysis of kidney stone formation in the Aprt knockout mouse

    Microsoft Academic Search

    Andrew P. Evan; Sharon B. Bledsoe; Bret A. Connors; Li Deng; Li Liang; Changshun Shao; Naomi S. Fineberg; Marc D. Grynpas; Peter J. Stambrook; Shao Youzhi; Amrik Sahota; Jay A. Tischfield

    2001-01-01

    Sequential analysis of kidney stone formation in the Aprt knockout mouse.BackgroundWe have previously shown that, as in human adenine phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8-dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more severe in male than in female mice. To examine the biological bases for these differences, the area occupied by DHA crystals was quantified

  16. Helicopter Human Factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control/display concepts; (6) Quantify, model, predict, and improve pilots, workload-management strategies; and (7) Design computer-game trainers to reduce training time and cost.

  17. Human Capital Accumulation: The Role of Human Resource Development.

    ERIC Educational Resources Information Center

    Garavan, Thomas N.; Morley, Michael; Gunnigle, Patrick; Collins, Eammon

    2001-01-01

    Presents definitions of intellectual and human capital. Examines human capital from the individual perspective (employability, performance, career development) and organization perspective (investment, ownership, knowledge management). Reviews papers in the theme issue. (Contains 117 references.) (SK)

  18. Dengue Virus Tropism in Humanized Mice Recapitulates Human Dengue Fever

    PubMed Central

    Mota, Javier; Rico-Hesse, Rebeca

    2011-01-01

    Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans. PMID:21695193

  19. Adsorption of Human Papillomavirus 16 to live human sperm

    E-print Network

    Ribbeck, Katharina

    Human Papillomaviruses (HPVs) are a diverse group of viruses that infect the skin and mucosal tissues of humans. A high-risk subgroup of HPVs is associated with virtually all cases of cervical cancer [1]–[3]. High-risk ...

  20. Allopurinol-mediated lignocellulose-derived microbial inhibitor tolerance by Clostridium beijerinckii during acetone-butanol-ethanol (ABE) fermentation.

    PubMed

    Ujor, Victor; Agu, Chidozie Victor; Gopalan, Venkat; Ezeji, Thaddeus Chukwuemeka

    2015-04-01

    In addition to glucans, xylans, and arabinans, lignocellulosic biomass hydrolysates contain significant levels of nonsugar components that are toxic to the microbes that are typically used to convert biomass to biofuels and chemicals. To enhance the tolerance of acetone-butanol-ethanol (ABE)-generating Clostridium beijerinckii NCIMB 8052 to these lignocellulose-derived microbial inhibitory compounds (LDMICs; e.g., furfural), we have been examining different metabolic perturbation strategies to increase the cellular reductant pools and thereby facilitate detoxification of LDMICs. As part of these efforts, we evaluated the effect of allopurinol, an inhibitor of NAD(P)H-generating xanthine dehydrogenase (XDH), on C. beijerinckii grown in furfural-supplemented medium and found that it unexpectedly increased the rate of detoxification of furfural by 1.4-fold and promoted growth, butanol, and ABE production by 1.2-, 2.5-, and 2-fold, respectively. Since NAD(P)H/NAD(P)(+) levels in C. beijerinckii were largely unchanged upon allopurinol treatment, we postulated and validated a possible basis in DNA repair to account for the solventogenic gains with allopurinol. Following the observation that supplementation of allopurinol in the C. beijerinckii growth media mitigates the toxic effects of nalidixic acid, a DNA-damaging antibiotic, we found that allopurinol elicited 2.4- and 6.7-fold increase in the messenger RNA (mRNA) levels of xanthine and hypoxanthine phosphoribosyltransferases, key purine-salvage enzymes. Consistent with this finding, addition of inosine (a precursor of hypoxanthine) and xanthine led to 1.4- and 1.7-fold increase in butanol production in furfural-challenged cultures of C. beijerinckii. Taken together, our results provide a purine salvage-based rationale for the unanticipated effect of allopurinol in improving furfural tolerance of the ABE-fermenting C. beijerinckii. PMID:25690312

  1. Challenging Corporate ‘Humanity’: Legal Disembodiment, Embodiment and Human Rights

    Microsoft Academic Search

    Anna Grear

    2007-01-01

    This article interrogates the corporate use of human rights discourse. It does so in light of concern surrounding corporate distortion of the Universal Declaration of Human Rights (UDHR) paradigm,1 and in light of the fact that corporations can claim shelter under human rights documents, particularly—as recently discussed by Emberland2—the European Convention of Human Rights and Fundamental Freedoms (ECHR). The author

  2. Do international human rights treaties improve respect for human rights?

    Microsoft Academic Search

    Eric Neumayer

    2004-01-01

    After the non-binding Universal Declaration of Human Rights, many global and regional human rights treaties have been concluded. Critics argue that these are unlikely to have made any actual difference in reality. Others contend that international regimes can improve respect for human rights in state parties, particularly in more democratic countries or countries with a strong civil society devoted to

  3. Do International Human Rights Treaties Improve Respect for Human Rights?

    Microsoft Academic Search

    Eric Neumayer

    2005-01-01

    After the nonbinding Universal Declaration of Human Rights, many global and regional human rights treaties have been concluded. Critics argue that these are unlikely to have made any actual difference in reality. Others contend that international regimes can improve respect for human rights in state parties, particularly in more democratic countries or countries with a strong civil society devoted to

  4. The Human Connectome: A Structural Description of the Human Brain

    Microsoft Academic Search

    Olaf Sporns; Giulio Tononi; Rolf Kötter

    2005-01-01

    T he connection matrix of the human brain (the human ''connectome'') represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large- scale anatomical connection patterns exist for other mammalian species, there is currently no connection

  5. HUMAN NUTRITION -FUNCTIONAL FOODS KNL030 Human Nutrition -Functional Foods

    E-print Network

    HUMAN NUTRITION - FUNCTIONAL FOODS KNL030 Human Nutrition - Functional Foods Poäng: 5.0 Betygskala grupparbeten. Litteratur: Garrow, J.S.; James, W.P.T.: Human nutrition and dietetics, 9th ed, Churchill Livingstone eller Whitney, E.S., Rolfes, S.R.: Understanding nutrition, 8th ed, 1999, West Publishing Company

  6. Human evolution: Origins of modern humans still look recent

    Microsoft Academic Search

    Todd R. Disotell

    1999-01-01

    That modern humans have a relatively ancient origin has been suggested on the basis of fossil and genetic evidence. But DNA sequences from an extinct neanderthal, and phylogenetic analyses of hundreds of human and ape sequences, continue to support a recent origin for modern humans.

  7. Human evolution: origins of modern humans still look recent.

    PubMed

    Disotell, T R

    1999-09-01

    That modern humans have a relatively ancient origin has been suggested on the basis of fossil and genetic evidence. But DNA sequences from an extinct neanderthal, and phylogenetic analyses of hundreds of human and ape sequences, continue to support a recent origin for modern humans. PMID:10508573

  8. Regenerative medicine and human models of human disease

    Microsoft Academic Search

    Kenneth R. Chien

    2008-01-01

    Recent advances in stem-cell technology are now allowing the mechanisms of human disease to be studied in human cells. A new era for regenerative medicine is arising from such disease models, extending beyond early cell-based therapies and towards evaluating genetic variation in humans and identifying the molecular pathways that lead to disease, as well as targets for therapy.

  9. The Human Condition: Medicine, Arts and Humanities Spring Quarter 2014

    E-print Network

    Straight, Aaron

    :15 to 4:05 This course is the Biomedical Ethics and Medical Humanities Scholarly Concentration gateway for medical students in the Biomedical Ethics and Medical Humanities Scholarly Concentration in order course for medical humanities. The course is open to all Stanford medical, graduate and undergraduate

  10. Zygomycetes in Human Disease

    PubMed Central

    Ribes, Julie A.; Vanover-Sams, Carolyn L.; Baker, Doris J.

    2000-01-01

    The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk factors. The Entomophthorales are closely related to the Mucorales on the basis of sexual growth by production of zygospores and by the production of coenocytic hyphae. Despite these similarities, the Entomophthorales and Mucorales have dramatically different gross morphologies, asexual reproductive characteristics, and disease manifestations. In comparison to the floccose aerial mycelium of the Mucorales, the Entomophthorales produce a compact, glabrous mycelium. The asexually produced spores of the Entomophthorales may be passively released or actively expelled into the environment. Human disease with these organisms occurs predominantly in tropical regions, with transmission occurring by implantation of spores via minor trauma such as insect bites or by inhalation of spores into the sinuses. Conidiobolus typically infects mucocutaneous sites to produce sinusitis disease, while Basidiobolus infections occur as subcutaneous mycosis of the trunk and extremities. The Entomophthorales are true pathogens, infecting primarily immunocompetent hosts. They generally do not invade blood vessels and rarely disseminate. Occasional cases of disseminated and angioinvasive disease have recently been described, primarily in immunocompromised patients, suggesting a possible emerging role for this organism as an opportunist. PMID:10756000

  11. A Survey of Human Computation Systems

    Microsoft Academic Search

    Man-ching Yuen; Ling-jyh Chen; Irwin King

    2009-01-01

    Human computation is a technique that makes use of human abilities for computation to solve problems. The human computation problems are the problems those computers are not good at solving but are trivial for humans. In this paper, we give a survey of various human computation systems which are categorized into initiatory human computation, distributed human computation and social game-based

  12. Phase resetting of human walking

    E-print Network

    Klenk, Daniel E

    2011-01-01

    This thesis is an investigation of the neural control of unimpaired human walking. Specifically, this work studied the potential for phase resetting of human walking by analyzing results from treadmill walking experiments. ...

  13. Climate Change and Human Health

    NSDL National Science Digital Library

    2011-05-02

    Learn how global climate change affects human health in this interactive activity adapted from A Human Health Perspective: On Climate Change by the National Institute of Environmental Health Sciences.

  14. Fire Control and Human Evolution.

    ERIC Educational Resources Information Center

    Russell, Claire

    1978-01-01

    Briefly outlines some aspects of the discovery of fire control by primitive people, such as the preadaptation for speech, the evolution of the human brain, and natural selection for human nakedness or loss of hair. (CS)

  15. DEMONSTRATION OF HUMAN EXPOSURE TOOLS

    EPA Science Inventory

    The Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientificall...

  16. Institutions, Human Capital, and Development

    E-print Network

    Acemoglu, Daron

    In this article, we revisit the relationship among institutions, human capital, and development. We argue that empirical models that treat institutions and human capital as exogenous are misspecified, both because of the ...

  17. Human Factors In Aircraft Automation

    NASA Technical Reports Server (NTRS)

    Billings, Charles

    1995-01-01

    Report presents survey of state of art in human factors in automation of aircraft operation. Presents examination of aircraft automation and effects on flight crews in relation to human error and aircraft accidents.

  18. Oceans and Human Health Center

    MedlinePLUS

    ocean and human health science can help prevent disease outbreaks and improve public health through a deeper understanding of the causes ... our Center and the field of oceans and human health science. More Research Learn about the research ...

  19. Two approaches to human rights

    E-print Network

    Holland, Sean Jamison

    2009-01-01

    Contemporary philosophy of human rights is dominated by two seemingly opposed approaches. This dissertation is concerned with the choice between them. The traditional approach to human rights is characterized by the belief ...

  20. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland) [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland)] [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)] [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland) [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: Veli-Matti.Kosma@uef.fi [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.