These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Herpes simplex virus-mediated human hypoxanthine-guanine phosphoribosyltransferase gene transfer into neuronal cells  

SciTech Connect

The virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, Lesch-Nyhan syndrome. Transfer of the HPRT gene into fibroblasts and lymphoblasts in vitro and into hematopoietic cells in vivo has been accomplished by other groups with retroviral-derived vectors. It appears to be necessary, however, to transfer the HPRT gene into neuronal cells to correct the neurological dysfunction of this disorder. The neurotropic virus herpes simplex virus type 1 has features that make it suitable for use as a vector to transfer the HPRT gene into neuronal tissue. This report describes the isolation of an HPRT-deficient rat neuroma cell line, designated B103-4C, and the construction of a recombinant herpes simplex virus type 1 that contained human HPRT cDNA. These recombinant viruses were used to infect B103-4C cells. Infected cells expressed HPRT activity which was human in origin.

Palella, T.D.; Silverman, L.J.; Schroll, C.T.; Homa, F.L.; Levine, M.; Kelley, W.N.

1988-01-01

2

Role of human hypoxanthine guanine phosphoribosyltransferase in activation of the antiviral agent T-705 (favipiravir).  

PubMed

6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is a novel antiviral compound with broad activity against influenza virus and diverse RNA viruses. Its active metabolite, T-705-ribose-5'-triphosphate (T-705-RTP), is recognized by influenza virus RNA polymerase as a substrate competing with GTP, giving inhibition of viral RNA synthesis and lethal virus mutagenesis. Which enzymes perform the activation of T-705 is unknown. We here demonstrate that human hypoxanthine guanine phosphoribosyltransferase (HGPRT) converts T-705 into its ribose-5'-monophosphate (RMP) prior to formation of T-705-RTP. The anti-influenza virus activity of T-705 and T-1105 (3-hydroxy-2-pyrazinecarboxamide; the analog lacking the 6-fluoro atom) was lost in HGPRT-deficient Madin-Darby canine kidney cells. This HGPRT dependency was confirmed in human embryonic kidney 293T cells undergoing HGPRT-specific gene knockdown followed by influenza virus ribonucleoprotein reconstitution. Knockdown for adenine phosphoribosyltransferase (APRT) or nicotinamide phosphoribosyltransferase did not change the antiviral activity of T-705 and T-1105. Enzymatic assays showed that T-705 and T-1105 are poor substrates for human HGPRT having Km(app) values of 6.4 and 4.1 mM, respectively. Formation of the RMP metabolites by APRT was negligible, and so was the formation of the ribosylated metabolites by human purine nucleoside phosphorylase. Phosphoribosylation and antiviral activity of the 2-pyrazinecarboxamide derivatives was shown to require the presence of the 3-hydroxyl but not the 6-fluoro substituent. The crystal structure of T-705-RMP in complex with human HGPRT showed how this compound binds in the active site. Since conversion of T-705 by HGPRT appears to be inefficient, T-705-RMP prodrugs may be designed to increase the antiviral potency of this new antiviral agent. PMID:23907213

Naesens, Lieve; Guddat, Luke W; Keough, Dianne T; van Kuilenburg, André B P; Meijer, Judith; Vande Voorde, Johan; Balzarini, Jan

2013-10-01

3

Characterization of in vivo somatic mutations at the hypoxanthine phosphoribosyltransferase gene of a human control population  

SciTech Connect

The ability to recognize a change in mutation spectrum after an exposure to a toxic substance and then relate that exposure to health risk depends on the knowledge of mutations that occur in the absence of exposure. The authors have been studying both the frequency and molecular nature of mutations of the hypoxanthine phosphoribosyltransferase (hprt) gene in peripheral blood lymphocytes as surrogate reporters of genetic damage. The authors have analyzed mutants, one per donor to ensure independence, from a control population in which the quantitative effect of smoking and age on mutant frequency have been well defined. Analyses of cDNA and genomic DNA by polymerase chain reaction and sequencing have identified the mutations in 63 mutants, 45 from males and 18 from females, of which 34 were smokers and 29 were nonsmokers. Slightly less than half of the mutations were base substitutions (28); they were predominantly at GC base pairs (19). Different mutations at the same site indicated that there are features of the hprt polypeptide that affect the mutation spectrum. Two pairs of identical mutations indicated that there may be hot spots. Mutations not previously reported have been detected, indicating that the mutation spectrum is only partly defined. The remainder of the mutations were deletions (32) or insertions/duplications (3); deletions ranged from one base pair to complete loss of the locus. Despite a small average increase in mutant frequency for smokers, an increased proportion of base substitutions at AT base pairs in smokers (p = 0.2) hinted at a smoking-associated shift in the mutation spectrum. Expanding the study to include individuals with larger, smoking-associated increases of mutant frequency will determine the significance of this observation. This background mutation study provides insight into factors that determine the mutation spectra of the hprt locus and provides data for comparison with mutation spectra of other populations. 44 refs., 7 tabs.

Burkhart-Schultz, K.; Thomas, C.B.; Brinson, E.; Jones, I.M. (Lawrence Livermore National Lab., CA (United States)); Thompson, C.L.; Strout, C.L. (National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States))

1993-04-22

4

Evidence for tetrameric structure of mammalian hypoxanthine phosphoribosyltransferase.  

PubMed

A fast electrophoretic variant of hypoxanthine phosphoribosyltransferase (HPRT) has been detected in Mus musculus bactrianus, a mouse subspecies from Middle Asia (USSR). The electrophoretic HPRT pattern yielded by hybrids between the somatic cell of LMTK- (deficient in thymidine kinase) and the splenocytes of a male of M. m. bactrianus was five-banded. The pattern obtained from the germ cells of the ovaries from 14.5-day-old embryos from laboratory CBA mice X M. m. bactrianus crosses was also composed of five bands. The hybrids between the somatic cells of human fibroblasts X LMTK- cells gave a three-banded electrophoretic HPRT pattern because the asymmetrical heteropolymeric isozymes are probably unstable. Taken together, all the evidence is in favor of a tetrameric structure of mammalian HPRT. PMID:3579865

Bochkarev, M N; Kulbakina, N A; Zhdanova, N S; Rubtsov, N B; Zakian, S M; Serov, O L

1987-02-01

5

Deletion and insertion in vivo somatic mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene of human T-lymphocytes  

SciTech Connect

Deletion and insertion mutations have been found to be a major component of the in vivo somatic mutation spectrum in the hypoxanthine phosphoribosyltransferase (hprt) gene of T-lymphocytes. In a population of 172 healthy people (average age, 34; mutant frequency, 10.3 x 10{sup -6}), deletion/insertion mutations constituted 41% (89) of the 217 independent mutations, the remainder being base substitutions. Mutations were identified by multiplex PCR assay of genomic DNA for exon regions, by sequencing cDNA, or sequencing genomic DNA. The deletion and insertion mutations were divided among {+-} 1 to 2 basepair (bp) frameshifts (14%, 30), small deletions and insertions of 3-200 bps (13%, 28), large deletions of one or more exons (12%, 27), and complex events (2%, 4). Frameshift mutations were dominated by -1 bp deletions (21 of 30). Exon 3 contained five frameshift mutations in the run of 6 Gs, the only site in the coding region with multiple frameshift mutations, possibly caused by strand dislocation during replication. Both endpoints were sequenced for 23 of the 28 small deletions/insertions including two tandem duplication events in exon 6. More small deletions (8/28), possibly mediated by trinucleotide repeats, occurred in exon 2 than in the other exons. Large deletions included total gene deletions (6), exon 2 + 3 deletions (4), and loss of multiple (9) and single exons (8) in genomic DNA. The diverse mutation spectrum indicates that multiple mechanisms operated at many different sequences and provides a resource for examination of deletion mutation. 68 refs.

Burkhart-Schultz, K.J.; Jones, I.M. [Lawrence Livermore National Lab., CA (United States)] [Lawrence Livermore National Lab., CA (United States)

1997-12-31

6

Hypoxanthine phosphoribosyltransferase: radiochemical assay procedures for the forward and reverse reactions  

SciTech Connect

Simple and rapid radiochemical assay procedures for the forward (IMP synthesis) and reverse (IMP pyrophosphorolysis) reactions catalyzed by hypoxanthine phosphoribosyltransferase have been developed. Enzyme activity in the forward direction was assessed by measuring the amount of (8-/sup 14/C)IMP formed from (8-/sup 14/C)hypoxanthine following their separation by polyethyleneimine-cellulose TLC in methanol:water (1:1, v/v). (8-/sup 14/C)IMP has been synthesized from (8-/sup 14/C)hypoxanthine, using hypoxanthine phosphoribosyltransferase derived from human brain, with subsequent purification by elution from phenyl boronate-agarose. Enzyme activity in the reverse direction was assessed by measuring the amount of (8-/sup 14/C)uric acid formed from the labeled IMP following their separation by polyethyleneimine-cellulose TLC in 0.2 M LiCl saturated with boric acid (pH 4.5):95% ethanol (1:1, v/v), the transferase reaction being coupled with excess xanthine oxidase and catalase to overcome the unfavorable equilibrium.

Smithers, G.W.; O'Sullivan, W.J.

1985-02-15

7

Nicotinamide Phosphoribosyltransferase in Human Diseases  

PubMed Central

Nicotinamide phosphoribosyltransferase (NAMPT) was first reported as a pre-B-cell colony enhancing factor in 1994 with little notice, but it has received increasing attention in recent years due to accumulating evidence indicating that NAMPT is a pleiotropic protein such as a growth factor, a cytokine, an enzyme and a visfatin. Now, NAMPT has been accepted as an official name of this protein. Because of NAMPT’s multiple functions in a variety of physiological processes, their dysregulations have been implicated in the pathogenesis of a number of human diseases or conditions such as acute lung injury, aging, atherosclerosis, cancer, diabetes, rheumatoid arthritis and sepsis. This review will cover the current understanding of NAMPT’s structure and functions with an emphasis on recent progress of nicotinamide phosphoribosyltransferase’s pathological roles in various human diseases and conditions. Future directions on exploring its Terra incognita will be offered in the end. PMID:22140607

Zhang, Li Qin; Heruth, Daniel P.; Ye, Shui Qing

2011-01-01

8

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

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

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

1999-01-01

9

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

PubMed Central

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

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

2013-01-01

10

Pre-thymic somatic mutation leads to high mutant frequency at hypoxanthine-guanine phosphoribosyltransferase gene  

SciTech Connect

While characterizing the background mutation spectrum of the Hypoxathine-guanine phosphoribosyltransferase (HPRT) gene in a healthy population, an outlier with a high mutant frequency of thioguanine resistant lymphocytes was found. When studied at the age of 46, this individual had been smoking 60 cigarettes per day for 38 years. His mutant frequency was calculated at 3.6 and 4.2x10{sup {minus}4} for two sampling periods eight months apart. Sequencing analysis of the HPRT gene in his mutant thioguanine resistant T lymphocytes was done to find whether the cells had a high rate of mutation, or if the mutation was due to a single occurrence of mutation and, if so, when in the T lymphocyte development the mutation occurred. By T-cell receptor analysis it has been found that out of 35 thioguanine resistant clones there was no dominant gamma T cell receptor gene rearrangement. During my appointment in the Science & Engineering Research Semester, I found that 34 of those clones have the same base substitution of G{yields}T at cDNA position 197. Due to the consistent mutant frequency from both sampling periods and the varying T cell receptors, the high mutant frequency cannot be due to recent proliferation of a mature mutant T lymphocyte. From the TCR and DNA sequence analysis we conclude that the G{yields}T mutation must have occurred in a T lymphocyte precursor before thymic differentiation so that the thioguanine resistant clones share the same base substitution but not the same gamma T cell receptor gene.

Jett, J. [Lawrence Livermore National Lab., CA (United States)

1994-12-01

11

Expression of transformation in cell hybrids. I. Isolation and application of density-inhibited Balb/3T3 cells deficient in hypoxanthine phosphoribosyltransferase and resistant to ouabain.  

PubMed

A cell line, THO2, was isolated from Balb/3T3 clone A31 after sequential nitrosoguanidine treatments and selection for resistance to 6-thioguanine and ouabain. THO2 retains the properties of density-dependent inhibition of growth and serum dependence of DNA synthesis characteristic of 3T3. The codominant expression of ouabain resistance and inability of THO2 to utilize exogenous hypoxanthine in the presence of aminopterin allows isolation of somatic cell hybrids involving THO2 and any ouabain-sensitive, hypoxanthine phosphoribosyltransferase-positive cell line. Hybrid clones derived from THO2 and SV40-transformed cells show dominant expression of the transformed phenotype with respect to multilayered arrangement of cells and ability to synthesize DNA in 1% calf-serum medium. PMID:1028169

Jha, K K; Ozer, H L

1976-05-01

12

A germ line mutation within the coding sequence for the putative 5-phosphoribosyl-1-pyrophosphate binding site of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in a Lesch-Nyhan patient: missense mutations within a functionally important region probably cause disease  

Microsoft Academic Search

Lesch-Nyhan syndrome caused by a complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) is the result of a heterogeneous group of germ line mutations. Identification of each mutant gene provides valuable information as to the type of mutation that occurs spontaneously. We report here a newly identified HPRT mutation in a Japanese patient with Lesch-Nyhan syndrome. This gene, designated HPRT Tokyo,

Shin Fujimori; Tetsuo Tagaya; Naoyuki Kamatani; Ieo Akaoka

1992-01-01

13

Partial Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency as the Unsuspected Cause of Renal Disease Spanning Three Generations: A Cautionary Tale  

Microsoft Academic Search

Hypoxanthine-guanine phosphoribosyl- transferase (HPRT) deficiency is an X-linked defect of purine metabolism. Clinical manifestations are usually related to the degree of enzyme deficiency: complete HPRT deficiency (Lesch-Nyhan syndrome) presenting with severe neurologic or renal symptoms, or partial HPRT deficiency (Kelley-Seegmiller syndrome) mani- festing as a gout-urolithiasis syndrome. A 3-generation kindred is described in which the recognition of partial HPRT deficiency

Persephone Augoustides-Savvopoulou; Fotis Papachristou; Lynette D. Fairbanks; Kostas Dimitrakopoulos; Anthony M. Marinaki; H. Anne Simmonds

2010-01-01

14

Synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme.  

PubMed

The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, (1)H NMR, (13)C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H 37 Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562-3.125 ?g/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues. PMID:23625031

Patel, Manishkumar B; Kumar, Sivakumar Prasanth; Valand, Nikunj N; Jasrai, Yogesh T; Menon, Shobhana K

2013-08-01

15

Isolation of mammalian cell mutants deficient in glucose-6-phosphate dehydrogenase activity: linkage to hypoxanthine phosphoribosyl transferase.  

PubMed Central

Mutants of Chinese hamster ovary cells deficient in glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP 1-oxidoreducatse, EC 1.1.1.49) activity were isolated after mutagenesis with ethyl methane sulfonate. The mutants were induced at frequencies of about 10-4 and do not differ in growth properties from wild-type cells. They were isolated by means of a sib selection technique coupled with a histochemical stain of colonies for enzyme activity. The lack of enzyme activity is not due to a dissociable inhibitor, and is recessive in hybrid cells. Multiple mutants that lack hypoxanthine phosphoribosyltransferase activity (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) and adenine phosphoribosyltransferase activity (AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) were isolated by further mutagenesis. By following segregation of wild-type phenotypes from heterozygous multiply marked hybrid cells, it was shown that the genes responsible for glucose-6-phosphate dehydrogenase activity and hypoxanthine phosphoribosyltransferase activity are linked in Chinese hamster cells, in agreement with the location of both on the X chromosome in humans. No linkage to adenosine phosphoribosyltransferase was found. The isolation of mutant cells carrying linked markers should prove useful for studying chromosomal events such as segregation, breakage, recombination, and X-chromosome reactivation. Images PMID:1054832

Rosenstraus, M; Chasin, L A

1975-01-01

16

Recycling nicotinamide. The transition-state structure of human nicotinamide phosphoribosyltransferase  

PubMed Central

Human nicotinamide phosphoribosyltransferase (NAMPT) replenishes the NAD pool and controls the activities of sirtuins (SIRT), mono- and poly-(ADP-ribose) polymerases (PARP) and NAD nucleosidase (CD38). The nature of the enzymatic transition-state (TS) is central to understanding the function of NAMPT. We determined the TS structure for pyrophosphorolysis of nicotinamide mononucleotide (NMN) by kinetic isotope effects (KIEs). With the natural substrates, NMN and pyrophosphate (PPi), the intrinsic KIEs of [1?-14C], [1-15N], [1?-3H] and [2?-3H] are 1.047, 1.029, 1.154 and 1.093, respectively. A unique quantum computational approach was used for TS analysis that included structural elements of the catalytic site. Without constraints (e.g. imposed torsion angles), the theoretical and experimental data are in good agreement. The quantum-mechanical calculations incorporated a crucial catalytic site residue (D313), two magnesium atoms and coordinated water molecules. The transition state model predicts primary 14C, ?-secondary 3H, ?-secondary 3H and primary 15N KIE close to the experimental values. The analysis reveals significant ribocation character at the TS. The attacking PPi nucleophile is weakly interacting (rC-O = 2.60 Å) and the N-ribosidic C1?-N bond is highly elongated at the TS (rC-N = 2.35 Å), consistent with an ANDN mechanism. Together with the crystal structure of the NMN•PPi•Mg2•enzyme complex, the reaction coordinate is defined. The enzyme holds the nucleophile and leaving group in relatively fixed positions to create a reaction coordinate with C1?-anomeric migration from nicotinamide to the PPi. The transition state is reached by a 0.85 Å migration of C1?. PMID:23373462

Burgos, Emmanuel S.; Vetticatt, Mathew J.; Schramm, Vern L.

2013-01-01

17

Recycling nicotinamide. The transition-state structure of human nicotinamide phosphoribosyltransferase.  

PubMed

Human nicotinamide phosphoribosyltransferase (NAMPT) replenishes the NAD pool and controls the activities of sirtuins, mono- and poly-(ADP-ribose) polymerases, and NAD nucleosidase. The nature of the enzymatic transition-state (TS) is central to understanding the function of NAMPT. We determined the TS structure for pyrophosphorolysis of nicotinamide mononucleotide (NMN) from kinetic isotope effects (KIEs). With the natural substrates, NMN and pyrophosphate (PPi), the intrinsic KIEs of [1'-(14)C], [1-(15)N], [1'-(3)H], and [2'-(3)H] are 1.047, 1.029, 1.154, and 1.093, respectively. A unique quantum computational approach was used for TS analysis that included structural elements of the catalytic site. Without constraints (e.g., imposed torsion angles), the theoretical and experimental data are in good agreement. The quantum-mechanical calculations incorporated a crucial catalytic site residue (D313), two magnesium atoms, and coordinated water molecules. The TS model predicts primary (14)C, ?-secondary (3)H, ?-secondary (3)H, and primary (15)N KIEs close to the experimental values. The analysis reveals significant ribocation character at the TS. The attacking PPi nucleophile is weakly interacting (r(C-O) = 2.60 Å), and the N-ribosidic C1'-N bond is highly elongated at the TS (r(C-N) = 2.35 Å), consistent with an A(N)D(N) mechanism. Together with the crystal structure of the NMN·PPi·Mg2·enzyme complex, the reaction coordinate is defined. The enzyme holds the nucleophile and leaving group in relatively fixed positions to create a reaction coordinate with C1'-anomeric migration from NAM to the PPi. The TS is reached by a 0.85 Å migration of C1'. PMID:23373462

Burgos, Emmanuel S; Vetticatt, Mathew J; Schramm, Vern L

2013-03-01

18

Effect of nucleoside transport inhibition on adenosine and hypoxanthine accumulation in the ischemic human myocardium.  

PubMed

The effect of nucleoside transport inhibition on the adenylate catabolism was studied in the human myocardium under normothermic ischemic conditions. Ten hearts from cardiac transplant recipients and two hearts from cardiac homograft donors were used in this study. The hearts were excised under hypothermic conditions (25 degrees C body temperature), the coronary arteries flushed with 500 ml ice-cold Ringer solution (n = 6; group I) or with ice-cold Ringer solution containing 1 mg/l of the nucleoside transport inhibitor R75231 (n = 6; group II). After transportation at 0 degree C from the operation room, the hearts were quickly rewarmed to 37 degrees C. Serial transmural biopsy specimens were taken during normothermic ischemia for determination of purine catabolites. The level of ATP before normothermic ischemia was 17.5 +/- 1.0 mumol/g dry weight in the control group (group I) and 19.3 +/- 0.4 mumol/g dry weight in the drug group. ATP, expressed as percentage of total purine content, was similar in both groups before rewarming (79.5 +/- 4.3% in group I and 79.5 +/- 2.9% in group II). There was no significant difference in the rate of ATP breakdown in both groups throughout the experiment (ATP was 3.0 +/- 1.4% of total purines in group I and 1.4 +/- 0.2% in group II at 120 min of normothermic ischemia). Adenine nucleotide content changed also similarly in both groups. Adenosine accumulation was, however, significantly higher in group II than in group I (peak values: 4.6 +/- 1.0% of total purines in group I vs 14.0 +/- 1.7% in group II; p < 0.01). The ratio between adenosine and inosine was significantly higher in group II throughout normothermic ischemia (p < 0.01). In spite of a larger accumulation of adenosine in group II, the increase in inosine was similar in both groups. We conclude that nucleoside transport inhibition significantly delays the breakdown of adenosine and the formation of hypoxanthine in the ischemic human myocardium. PMID:8215716

Masuda, M; Sukehiro, S; Möllhoff, T; Van Belle, H; Flameng, W

1993-01-01

19

A new method for the determination of adenine phosphoribosyltransferase activity in human erythrocytes by reversed phase high performance liquid chromatography.  

PubMed

A new method for the determination of adenine phosphoribosyltransferase (APRT) activity in human erythrocytes is described. APRT activity was assayed by a non-radiochemical method in which adenosine monophosphate (AMP) and AMP metabolites produced from a substrate adenine were converted to inosine by alkaline phosphatase and adenosine deaminase. The inosine thus produced was quantitated by reversed phase HPLC. This method was simple, precise, sensitive and free from interference with other co-existing erythrocyte enzymes. Four patients with 2,8-dihydroxyadenine urolithiasis and others with several disorders in purine metabolism have been studied, showing that the present method is clinically useful for the diagnosis and the evaluation of the severity of some human diseases. PMID:1868258

Kojima, T; Nishina, T; Kitamura, M; Yamanak, H; Nishioka, K

1991-03-01

20

Mitotic Separation of Two Human X-Linked Genes in Man--Mouse Somatic Cell Hybrids  

Microsoft Academic Search

Six interspecific somatic hybrid cell lines were derived from a mouse line deficient in hypoxanthine: guanine phosphoribosyltransferase (HGPRT) and human diploid cells with normal enzyme activity. Human HGPRT was present in all six hybrids and the clones derived from them. However, in two of the six, and in some clones from another two, human glucose-6-phosphate dehydrogenase (G6PD) was absent. Since

O. J. Miller; P. R. Cook; P. Meera Khan; S. Shin; M. Siniscalco

1971-01-01

21

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 ...

22

Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT), an Enzyme Essential for NAD+ Biosynthesis, in Human Cancer Cells  

PubMed Central

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD+, essential for cellular metabolism, energy production, and DNA repair. NAMPT has been extensively studied because of its critical role in these cellular processes and the prospect of developing therapeutics against the target, yet how it regulates cellular metabolism is not fully understood. In this study we utilized liquid chromatography-mass spectrometry to examine the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and serine biosynthesis in cancer cells and tumor xenografts. We show for the first time that NAMPT inhibition leads to the attenuation of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step due to the reduced availability of NAD+ for the enzyme. The attenuation of glycolysis results in the accumulation of glycolytic intermediates before and at the glyceraldehyde 3-phosphate dehydrogenase step, promoting carbon overflow into the pentose phosphate pathway as evidenced by the increased intermediate levels. The attenuation of glycolysis also causes decreased glycolytic intermediates after the glyceraldehyde 3-phosphate dehydrogenase step, thereby reducing carbon flow into serine biosynthesis and the TCA cycle. Labeling studies establish that the carbon overflow into the pentose phosphate pathway is mainly through its non-oxidative branch. Together, these studies establish the blockade of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step as the central metabolic basis of NAMPT inhibition responsible for ATP depletion, metabolic perturbation, and subsequent tumor growth inhibition. These studies also suggest that altered metabolite levels in tumors can be used as robust pharmacodynamic markers for evaluating NAMPT inhibitors in the clinic. PMID:23239881

Tan, Bo; Young, Debra A.; Lu, Zhao-Hai; Wang, Tao; Meier, Timothy I.; Shepard, Robert L.; Roth, Kenneth; Zhai, Yan; Huss, Karen; Kuo, Ming-Shang; Gillig, James; Parthasarathy, Saravanan; Burkholder, Timothy P.; Smith, Michele C.; Geeganage, Sandaruwan; Zhao, Genshi

2013-01-01

23

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...

24

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...

25

Chromosome-mediated transfer of murine alleles for hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and ouabain resistance into human cell lines  

Microsoft Academic Search

Genetic drug-resistance markers were transferred via purified metaphase chromosomes from mouse L cells into the human fibrosarcoma line HT1080 and HeLa S3 cells. Interspecific chromosome-mediated transfer of hypoxanthine-guanine phosphoribosyl transferase (HGPRT; EC 2.4.2.8) from mouse L cells into HGPRT- HT1080 cells occurred at a frequency of approximately 1×10-7. The presence of the mouse allele for HGPRT in transferent isolates was

Tracy Gross Lugo; Raymond M. Baker

1985-01-01

26

Fragment-based identification of amides derived from trans-2-(pyridin-3-yl)cyclopropanecarboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).  

PubMed

Potent, trans-2-(pyridin-3-yl)cyclopropanecarboxamide-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using fragment-based screening and structure-based design techniques. Multiple crystal structures were obtained of initial fragment leads, and this structural information was utilized to improve the biochemical and cell-based potency of the associated molecules. Many of the optimized compounds exhibited nanomolar antiproliferative activities against human tumor lines in in vitro cell culture experiments. In a key example, a fragment lead (13, KD = 51 ?M) was elaborated into a potent NAMPT inhibitor (39, NAMPT IC50 = 0.0051 ?M, A2780 cell culture IC50 = 0.000?49 ?M) which demonstrated encouraging in vivo efficacy in an HT-1080 mouse xenograft tumor model. PMID:24405419

Giannetti, Anthony M; Zheng, Xiaozhang; Skelton, Nicholas J; Wang, Weiru; Bravo, Brandon J; Bair, Kenneth W; Baumeister, Timm; Cheng, Eric; Crocker, Lisa; Feng, Yezhen; Gunzner-Toste, Janet; Ho, Yen-Ching; Hua, Rongbao; Liederer, Bianca M; Liu, Yongbo; Ma, Xiaolei; O'Brien, Thomas; Oeh, Jason; Sampath, Deepak; Shen, Youming; Wang, Chengcheng; Wang, Leslie; Wu, Hongxing; Xiao, Yang; Yuen, Po-wai; Zak, Mark; Zhao, Guiling; Zhao, Qiang; Dragovich, Peter S

2014-02-13

27

The Mutational Spectrum of the HPRT Gene from Human T Cells in Vivo Shares a Significant Concordant Set of Hot Spots with MNNG-treated Human Cells1  

Microsoft Academic Search

The preponderance of G:C to A:T transitions in inherited and somatic human mutations has led to the hypothesis that some of these mutations arise as a result of formation of O6-methylguanine in DNA. To test this hypothesis, the fine structure map of N-methyl-N'-nitro-N-nitrosoguani- dine (MNNG)-induced mutations was determined in human lymphoblas- toid cells in the human hypoxanthine-guanine-phosphoribosyltransferase (HPRT) gene and

Aoy Tomita-Mitchell; Losee Lucy Ling; Curtis L. Glover; Jacklene Goodluck-Griffith; William G. Thilly

2003-01-01

28

Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).  

PubMed

The fragment-based identification of two novel and potent biochemical inhibitors of the nicotinamide phosphoribosyltransferase (NAMPT) enzyme is described. These compounds (51 and 63) incorporate an amide moiety derived from 3-aminopyridine, and are thus structurally distinct from other known anti-NAMPT agents. Each exhibits potent inhibition of NAMPT biochemical activity (IC50=19 and 15 nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50=121 and 99 nM, respectively). However, additional biological studies indicate that only inhibitor 51 exerts its A2780 cell culture effects via a NAMPT-mediated mechanism. The crystal structures of both 51 and 63 in complex with NAMPT are also independently described. PMID:24433859

Dragovich, Peter S; Zhao, Guiling; Baumeister, Timm; Bravo, Brandon; Giannetti, Anthony M; Ho, Yen-Ching; Hua, Rongbao; Li, Guangkun; Liang, Xiaorong; Ma, Xiaolei; O'Brien, Thomas; Oh, Angela; Skelton, Nicholas J; Wang, Chengcheng; Wang, Weiru; Wang, Yunli; Xiao, Yang; Yuen, Po-wai; Zak, Mark; Zhao, Qiang; Zheng, Xiaozhang

2014-02-01

29

High rate of mutation reporter gene inactivation during human T cell proliferation  

Microsoft Academic Search

Caspase activation and degradation of deoxyribonucleic acid (DNA) damage response factors occur during in vitro T-cell proliferation,\\u000a and an increased frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT)-negative variants have been reported in\\u000a conditions associated with in vivo T-cell proliferation. We have applied two human somatic cell mutation reporter assays,\\u000a for the HPRT and phosphatidylinositol glycan class A (PIG-A) genes, to human T

Aida Gabdoulkhakova; Gunnel Henriksson; Nadezhda Avkhacheva; Alexander Sofin; Anders Bredberg

2007-01-01

30

Extracellular ATP induces P2X7-dependent nicotinamide phosphoribosyltransferase release in LPS-activated human monocytes.  

PubMed

Nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in NAD biosynthesis, has recently been identified as a novel mediator of innate immunity. In the present study, we report that treatment of LPS-primed monocytes with ATP greatly enhanced the secretion of NAMPT in a time- and concentration-dependent manner without displaying any cytotoxic effect. NAMPT release was suppressed by pretreatment with the P2X(7) receptor (P2X(7)R) inhibitors oxidized ATP (oxATP) and KN-62, indicating the engagement of P2X(7)Rs. Furthermore, P2X(7)R was found to be involved in mediating cell permeability caused by the addition of ATP. To define a role of endogenous ATP in NAMPT secretion, LPS-primed monocytes were incubated in the presence of oxATP and KN-62, as well as the ATP-hydrolyzing enzymes apyrase and hexokinase. With the exception of oxATP, neither substance led to a decrease in NAMPT release, suggesting that autocrine/paracrine ATP is unlikely to be responsible for the LPS-induced release of NAMPT. In conclusion, the enhanced release of NAMPT by extracellular ATP described here indicates the requirement of a second stimulus for the efficient secretion of NAMPT. This mode of secretion, which also applies to IL-1?, might represent a general mechanism for the release of leaderless secretory proteins at locally restricted sites. PMID:22377803

Schilling, Erik; Hauschildt, Sunna

2012-10-01

31

Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).  

PubMed

Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained. PMID:24021463

Zheng, Xiaozhang; Bair, Kenneth W; Bauer, Paul; Baumeister, Timm; Bowman, Krista K; Buckmelter, Alexandre J; Caligiuri, Maureen; Clodfelter, Karl H; Feng, Yezhen; Han, Bingsong; Ho, Yen-Ching; Kley, Nikolai; Li, Hong; Liang, Xiaorong; Liederer, Bianca M; Lin, Jian; Ly, Justin; O'Brien, Thomas; Oeh, Jason; Oh, Angela; Reynolds, Dominic J; Sampath, Deepak; Sharma, Geeta; Skelton, Nicholas; Smith, Chase C; Tremayne, Jarrod; Wang, Leslie; Wang, Weiru; Wang, Zhongguo; Wu, Hongxing; Wu, Jiansheng; Xiao, Yang; Yang, Guangxing; Yuen, Po-wai; Zak, Mark; Dragovich, Peter S

2013-10-15

32

EVIDENCE FOR INTERGENIC COMPLEMENTATION IN HYBRID CELLS DERIVED FROM TWO HUMAN DIPLOID STRAINS EACH CARRYING AN X-LINKED MUTATION*  

PubMed Central

Two male diploid fibroblast strains, each carrying deficiency mutations at different X-linked loci (glucose-6-phosphate dehydrogenase and hypoxanthine-guanine-phosphoribosyltransferase) have been successfully hybridized. The resulting mononucleated hybrid cells have been shown to synthesize both normal gene products, indicating that both X chromosomes are functionally active in the hybrid cells. We believe this is the first reported example of intergenic complementation in fused human diploid cells. Images PMID:5257005

Siniscalco, Marcello; Klinger, Harold P.; Eagle, Harry; Koprowski, Hilary; Fujimoto, Wilfred Y.; Seegmiller, J. Edwin

1969-01-01

33

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

PubMed

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

Torres, Rosa J; Puig, Juan G

2007-01-01

34

Interaction of the recombinant human methylpurine-DNA glycosylase (MPG protein) with oligodeoxyribonucleotides containing either hypoxanthine or abasic sites  

Microsoft Academic Search

Methylpurine-DNA glycosylases (MPG proteins, 3-methyladenine-DNA glycosylases) excise numerous damaged bases from DNA during the first step of base excision repair. The damaged bases removed by these proteins include those induced by both alkylating agents and\\/or oxidizing agents. The intrinsic kinetic parameters (kcat and Km) for the excision of hypoxan- thine by the recombinant human MPG protein from a 39 bp

Feng Miao; Mohammed Bouziane; Timothy R. O'Connor

1998-01-01

35

Spectrum of somatic mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene of healthy people  

SciTech Connect

We are studying the spectrum of mutation in a healthy, unexposed population in order to understand the nature of somatic mutation in the absence of major environmental exposures. Smokers (n = 82; average mutant frequency 10.9x10{sup -6}, average age 35 years) and nonsmokers (n = 46; average mutant frequency 8.1x10{sup -6}, average age 29 years) are included in this population in which mutant frequency depends on both age and years of smoking. PCR amplified cDNA and genomic DNA were sequenced to define the mutation in one mutant per person. OVerall there were 67 base substitutions (42 at GC pairs, 25 at AT pairs; 38 transversions, 27 transitions, 2 tandems), 22 deletions of 3 to 200bp, 19 larger deletions (ranging to >1 megabase, including 2 recombinase mediated events), 16 frameshifts of 1 to 2 bp, 2 insertions/duplications, and 2 complex changes. 21% (27) were exact repeat mutations, 2 to 3 at each of 9 {open_quotes}hotspots{close_quotes}. In all 6 cases of G to T transversions (3 each in smokers and nonsmokers), G was in the nontranscribed strand. There were two CC to TT tandem changes, one each in the transcribed and the nontranscribed strand, one in a smoker and one in a nonsmoker. There was a trend to more events at AT pairs of smokers and nonsmokers (p = 0.13). A change of T to G at coding position 146 seen in 3 of our smokers has previously been seen in a nonsmoker. Type of mutation, age of donor, and mutant frequency were not correlated. The mutation spectrum in this control population reveals the richness of mechanisms by which cells misprocess DNA and misrepair damaged DNA, and the difficulty of discriminating between mutations caused by errors of DNA metabolism and by exogenous and endogenous toxic agents.

Burkhart-Schultz, K.; Thomas, C.B.; Tucker, B.; Strout, C.L.; Jones, I.M. [Lawrence Livermore National Lab., CA (United States); Thompson, C.L.; Fuscoe, J.C. [Integrated Laboratory Systems, Research Triangle Park, NC (United States)

1994-12-31

36

Cell cycle-specific mutagenesis at the hypoxanthine phosphoribosyltransferase locus in adult rat liver epithelial cells.  

PubMed

The cell cycle specificity of chemical mutagenesis was studied by use of two cell synchronization techniques, one a nontoxic technique involving serum deprivation and the other a double thymidine block, to obtain rat liver epithelial cells in different phases of the cell cycle to be exposed to chemical mutagens. For both methyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine, there was a cell cycle specificity of chemical mutagenesis, with the most sensitive phase being the period of DNA synthesis. PMID:6938982

Tong, C; Fazio, M; Williams, G M

1980-12-01

37

Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).  

PubMed

Potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors containing 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas were identified using structure-based design techniques. The new compounds displayed improved aqueous solubilities, determined using a high-throughput solubility assessment, relative to previously disclosed urea and amide-containing NAMPT inhibitors. An optimized 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived compound exhibited potent anti-NAMPT activity (18; BC NAMPT IC50 = 11 nM; PC-3 antiproliferative IC50 = 36 nM), satisfactory mouse PK properties, and was efficacious in a PC-3 mouse xenograft model. The crystal structure of another optimized compound (29; NAMPT IC50 = 10nM; A2780 antiproliferative IC50 = 7 nM) in complex with the NAMPT protein was also determined. PMID:23899614

Dragovich, Peter S; Bair, Kenneth W; Baumeister, Timm; Ho, Yen-Ching; Liederer, Bianca M; Liu, Xiongcai; Liu, Yongbo; O'Brien, Thomas; Oeh, Jason; Sampath, Deepak; Skelton, Nicholas; Wang, Leslie; Wang, Weiru; Wu, Hongxing; Xiao, Yang; Yuen, Po-Wai; Zak, Mark; Zhang, Lei; Zheng, Xiaozhang

2013-09-01

38

Xanthine phosphoribosyltransferase from Leishmania donovani. Molecular cloning, biochemical characterization, and genetic analysis.  

PubMed

Xanthine phosphoribosyltransferase (XPRT) from Leishmania donovani is a unique enzyme that lacks a mammalian counterpart and is, therefore, a potential target for antiparasitic therapy. To investigate the enzyme at the molecular and biochemical level, a cDNA encoding the L. donovani XPRT was isolated by functional complementation of a purine auxotroph of Escherichia coli that also harbors deficiencies in the prokaryotic phosphoribosyltransferase (PRT) activities. The cDNA was then used to isolate the XPRT genomic clone. XPRT encodes a 241-amino acid protein exhibiting approximately 33% amino acid identity with the L. donovani hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and significant homology with other HGPRT family members. Southern blot analysis revealed that XPRT was a single copy gene that co-localized with HGPRT within a 4.3-kilobase pair (kb) EcoRI fragment, implying that the two genes arose as a result of an ancestral duplication event. Sequencing of this EcoRI fragment confirmed that HGPRT and XPRT were organized in a head-to-tail arrangement separated by an approximately 2.2-kb intergenic region. Both the 3.2-kb XPRT mRNA and XPRT enzyme were significantly up-regulated in Deltahgprt and Deltahgprt/Deltaaprt L. donovani mutants. Genetic obliteration of the XPRT locus by targeted gene replacement indicated that XPRT was not an essential gene under most conditions and that the Deltaxprt null strain was competent of salvaging all purines except xanthine. XPRT was overexpressed in E. coli and the recombinant protein purified to homogeneity. Kinetic analysis revealed that the XPRT preferentially phosphoribosylated xanthine but could also recognize hypoxanthine and guanine. K(m) values of 7.1, 448.0, and >100 microM and k(cat) values of 3.5, 2.6, and approximately 0.003 s(-1) were calculated for xanthine, hypoxanthine, and guanine, respectively. The XPRT gene and XPRT protein provide the requisite molecular and biochemical reagents for subsequent studies to validate XPRT as a potential therapeutic target. PMID:10567419

Jardim, A; Bergeson, S E; Shih, S; Carter, N; Lucas, R W; Merlin, G; Myler, P J; Stuart, K; Ullman, B

1999-11-26

39

Pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT), an enzyme essential for NAD+ biosynthesis, in human cancer cells: metabolic basis and potential clinical implications.  

PubMed

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for cellular metabolism, energy production, and DNA repair. NAMPT has been extensively studied because of its critical role in these cellular processes and the prospect of developing therapeutics against the target, yet how it regulates cellular metabolism is not fully understood. In this study we utilized liquid chromatography-mass spectrometry to examine the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and serine biosynthesis in cancer cells and tumor xenografts. We show for the first time that NAMPT inhibition leads to the attenuation of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step due to the reduced availability of NAD(+) for the enzyme. The attenuation of glycolysis results in the accumulation of glycolytic intermediates before and at the glyceraldehyde 3-phosphate dehydrogenase step, promoting carbon overflow into the pentose phosphate pathway as evidenced by the increased intermediate levels. The attenuation of glycolysis also causes decreased glycolytic intermediates after the glyceraldehyde 3-phosphate dehydrogenase step, thereby reducing carbon flow into serine biosynthesis and the TCA cycle. Labeling studies establish that the carbon overflow into the pentose phosphate pathway is mainly through its non-oxidative branch. Together, these studies establish the blockade of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step as the central metabolic basis of NAMPT inhibition responsible for ATP depletion, metabolic perturbation, and subsequent tumor growth inhibition. These studies also suggest that altered metabolite levels in tumors can be used as robust pharmacodynamic markers for evaluating NAMPT inhibitors in the clinic. PMID:23239881

Tan, Bo; Young, Debra A; Lu, Zhao-Hai; Wang, Tao; Meier, Timothy I; Shepard, Robert L; Roth, Kenneth; Zhai, Yan; Huss, Karen; Kuo, Ming-Shang; Gillig, James; Parthasarathy, Saravanan; Burkholder, Timothy P; Smith, Michele C; Geeganage, Sandaruwan; Zhao, Genshi

2013-02-01

40

Regulation of hypoxanthine transport in Neurospora crassa  

E-print Network

strain, intermediate activity levels. Ion-exchange chromatography of + the growth media revealed that in the presence of NH4, the ad-8 strain excreted hypoxanthine or inosine; the ad-1 strain did not ex- crete any detectable purines; and the double... mutant strain excreted + uric acid. In the absence of NH, none of the strains excreted any detectable purine compourds. iv ACKNOWLEDGEMENTS The author wishes to express his grateful appreciation to all the members of his committee: Drs. Clint W...

Sabina, Richard Lee

2012-06-07

41

Dihydroxyadenine Urolithiasis in Children with Partial Deficiency of Adenine Phosphoribosyltransferase  

Microsoft Academic Search

Urolithiasis composed of 2,8-dihydroxyadenine is not only formed in a complete defect of adenine phosphoribosyltransferase, but also in a partial deficiency of this enzyme. To our knowledge these cases reported in this paper are the third and fourth cases of dihydroxyadenine urinary calculi in patients with partial deficiency of adenine phosphoribosyltransferase.

Kimitaka Sakamoto; Yasuhito Fujisawa; Akio Ohmori; Kaoru Minoda; Hisashi Yamanaka; Kusuki Nishioka

1981-01-01

42

Trypanosoma brucei adenine-phosphoribosyltransferases mediate adenine salvage and aminopurinol susceptibility but not adenine toxicity?  

PubMed Central

African trypanosomes, like all obligate parasitic protozoa, cannot synthesize purines de novo and import purines from their hosts to build nucleic acids. The purine salvage pathways of Trypanosoma brucei being redundant, none of the involved enzymes is likely to be essential. Nevertheless they can be of pharmacological interest due to their role in activation of purine nucleobase or nucleoside analogues, which only become toxic when converted to nucleotides. Aminopurine antimetabolites, in particular, are potent trypanocides and even adenine itself is toxic to trypanosomes at elevated concentrations. Here we report on the T. brucei adenine phosphoribosyltransferases TbAPRT1 and TbAPRT2, encoded by the two genes Tb927.7.1780 and Tb927.7.1790, located in tandem on chromosome seven. The duplication is syntenic in all available Trypanosoma genomes but not in Leishmania. While TbAPRT1 is cytosolic, TbAPRT2 possesses a glycosomal targeting signal and co-localizes with the glycosomal marker aldolase. Interestingly, the distribution of glycosomal targeting signals among trypanosomatid adenine phosphoribosyltransferases is not consistent with their phylogeny, indicating that the acquisition of adenine salvage to the glycosome happened after the radiation of Trypanosoma. Double null mutant T. brucei ?tbaprt1,2 exhibited no growth phenotype but no longer incorporated exogenous adenine into the nucleotide pool. This, however, did not reduce their sensitivity to adenine. The ?tbaprt1,2 trypanosomes were resistant to the adenine isomer aminopurinol, indicating that it is activated by phosphoribosyl transfer. Aminopurinol was about 1000-fold more toxic to bloodstream-form T. brucei than the corresponding hypoxanthine isomer allopurinol. Aminopurinol uptake was not dependent on the aminopurine permease P2 that has been implicated in drug resistance. PMID:24596669

Lüscher, Alexandra; Lamprea-Burgunder, Estelle; Graf, Fabrice E.; de Koning, Harry P.; Mäser, Pascal

2013-01-01

43

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

PubMed Central

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 the presence of predators have been successfully utilized in such research. Zebrafish has been shown to respond to its natural alarm substance with species-typical fear reactions. However, the extraction of this alarm substance and ascertaining its consistent dosing has been problematic. A synthetic substance with a known chemical identity and molecular weight would allow precise dosing and experimental control. Previously, the chemical component, hypoxanthine 3-N-oxide, common to several fish alarm substances has been identified and has been shown to elicit alarm reactions in fish species belonging to the Osteriophysan superorder. In the current study we investigate the effect of hypoxanthine 3-N-oxide by exposing zebrafish to three different concentrations of this synthetic substance. Our results show that the substance efficaciously induces species-typical fear reactions increasing the number of erratic movement episodes and jumps in zebrafish. We discuss the translational relevance of our findings and conclude that hypoxanthine 3-N-oxide will have utility to elicit fear responses in the laboratory in a precisely controlled manner in zebrafish. PMID:19583985

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

2009-01-01

44

Molecular characterization of 15 rearrangements among 90 human in vivo somatic mutants shows that deletions predominate.  

PubMed Central

Ninety hypoxanthine phosphoribosyltransferase-deficient mutants were isolated from lymphocytes of 31 individuals drawn from both control populations and populations exposed to low doses of ionizing radiation. Southern analysis of the DNA revealed altered hybridization patterns in 15 mutants. Of these, 14 changes consisted of deletions of 2 to 40 kilobases or more. Images PMID:3821735

Bradley, W E; Gareau, J L; Seifert, A M; Messing, K

1987-01-01

45

The use of bromodeoxyuridine labeling in the human lymphocyte HGPRT somatic mutation assay.  

PubMed

The autoradiographic assay developed by Strauss and Albertini (1979) to quantitate human in vivo somatic mutation at the hypoxanthine guanine phosphoribosyl-transferase locus uses tritiated thymidine to identify mutant cells by their ability to pass through 'S' phase in the presence of 6-thioguanine. An alternative method, based on the incorporation of bromodeoxyuridine (BrdUrd) into the DNA of proliferative cells, followed by differential staining with the fluorescence-plus-Giemsa method, was used to identify 3 classes of lymphocyte nuclei: (a) small darkly stained nuclei, (b) large, reddish-colored nuclei with an apparent nucleolus, and (c) large, bluish-colored nuclei. By double labeling with BrdUrd and tritiated thymidine, it was determined that only the nuclei of the third class had incorporated BrdUrd. These results demonstrate that the technique used for sister-chromatid differentiation can be used to detect putative HGPRT mutants and to determine variant frequencies at the HGPRT locus. PMID:3627157

Ostrosky-Wegman, P; Montero, M R; de Nava, C C; Tice, R R; Albertini, R

1987-01-01

46

Use of double-replacement gene targeting to replace the murine alpha-lactalbumin gene with its human counterpart in embryonic stem cells and mice.  

PubMed

The mouse alpha-lactalbumin gene has been replaced with the human gene by two consecutive rounds of gene targeting in hypoxanthine phosphoribosyltransferase (HPRT)-deficient feeder-independent murine embryonic stem (ES) cells. One mouse alpha-lactalbumin allele was first replaced by an HPRT minigene which was in turn replaced by human alpha-lactalbumin. The end result is a clean exchange of defined DNA fragments with no other DNA remaining at the target locus. Targeted ES cells at each stage remained capable of contributing efficiently to the germ line of chimeric animals. Double replacement using HPRT-deficient ES cells and the HPRT selection system is therefore a powerful and flexible method of targeting specific alterations to animal genes. A typical strategy for future use would be to generate a null mutation which could then be used to produce multiple second-step alterations at the same locus. PMID:8289781

Stacey, A; Schnieke, A; McWhir, J; Cooper, J; Colman, A; Melton, D W

1994-02-01

47

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...

48

Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis.  

PubMed Central

Adenine phosphoribosyltransferase (APRT) deficiency in humans is an autosomal recessive syndrome characterized by the urinary excretion of adenine and the highly insoluble compound 2,8-dihydroxyadenine (DHA) that can produce kidney stones or renal failure. Targeted homologous recombination in embryonic stem cells was used to produce mice that lack APRT. Mice homozygous for a null Aprt allele excrete adenine and DHA crystals in the urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds. Thus, biochemical and histological changes in these mice mimic the human disease and provide a suitable model of human hereditary nephrolithiasis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8643571

Engle, S J; Stockelman, M G; Chen, J; Boivin, G; Yum, M N; Davies, P M; Ying, M Y; Sahota, A; Simmonds, H A; Stambrook, P J; Tischfield, J A

1996-01-01

49

Mechanism of Feedback Allosteric Inhibition of ATP Phosphoribosyltransferase  

PubMed Central

MtATP-phosphoribosyltransferase catalyzes the first and committed step in l-histidine biosynthesis in Mycobacterium tuberculosis and is therefore subjected to allosteric feedback regulation. Because of its essentiality, this enzyme is being studied as a potential target for novel anti-infectives. To understand the basis for its regulation, we characterized the allosteric inhibition using gel filtration, steady-state and pre-steady-state kinetics, and the pH dependence of inhibition and binding. Gel filtration experiments indicate that MtATP-phosphoribosyltransferase is a hexamer in solution, in the presence or absence of l-histidine. Steady-state kinetic studies demonstrate that l-histidine inhibition is uncompetitive versus ATP and noncompetitive versus PRPP. At pH values close to neutrality, a Kii value of 4 ?M was obtained for l-histidine. Pre-steady-state kinetic experiments indicate that chemistry is not rate-limiting for the overall reaction and that l-histidine inhibition is caused by trapping the enzyme in an inactive conformation. The pH dependence of binding, obtained by nuclear magnetic resonance, indicates that l-histidine binds better as the neutral ?-amino group. The pH dependence of inhibition (Kii), on the contrary, indicates that l-histidine better inhibits MtATP-phosphoribosytransferase with a neutral imidazole and an ionized ?-amino group. These results are combined into a model that accounts for the allosteric inhibition of MtATP-phosphoribosyltransferase. PMID:22989207

2012-01-01

50

An amperometric hypoxanthine biosensor based on Au@FeNPs for determination of hypoxanthine in meat samples.  

PubMed

A xanthine oxidase (XOD) from buttermilk was immobilized covalently onto boronic acid functionalized gold coated iron nanoparticles (Au@FeNPs) electrodeposited on pencil graphite (PG) electrode, via the boroester linkages, between free hydroxyl groups of boronic acid, ?-COOH and -NH2 groups of enzyme. The surface functionalization of Fe/Au nanoparticles with boronic acid (Au@FeNPs) on pencil graphite (PG) electrode was characterized by Fourier transform infrared (FTIR), cyclic voltammetry (CV), scanning electron microscopy (SEM), atomic force microscopy (AFM) and Electrochemical impedance spectroscopy (EIS) before and after immobilization of XOD. The biosensor exhibited optimum response within 3s at pH 7.2 and 30 °C and linearity in the range, 0.05 ?M to 150 ?M for hypoxanthine with a detection limit of 0.05 ?M (S/N=3). Apparent Michaelis Menten constant (Km(app)) for hypoxanthine was 40 ?M and Imax 0.125 mA. The biosensor was employed to determine hypoxanthine in fish, chicken, pork, beef meat and lost 50% of its initial activity after its 200 uses over 100 days, when stored at 4 °C. PMID:24140402

Devi, Rooma; Yadav, Sujata; Nehra, Renuka; Pundir, C S

2013-11-01

51

Regulatory elements in the introns of the human HPRT gene are necessary for its expression in embryonic stem cells  

SciTech Connect

The authors have examined the expression of transfected human hypoxanthine phosphoribosyltransferase minigenes (HPRT) in mouse embryonic stem (ES) cells. cDNA constructs of this gene that have been successfully used in somatic cell lines failed to confer hypoxanthine/aminopterin/thymidine (HAT) resistance in ES cells. In contrast, constructs containing introns 1 and 2 from the HPRT gene produced a high frequency of HAT-resistant colonies. This observation allowed them to identify two sequences in these introns that influence expression of the HPRT gene in ES cells. One element, located in intron 2, is required for effective HPRT expression in thee cells; the other element, located in intron 1, acts as an enhancer of HPRT expression. Using this information, they have constructed an HPRT minigene that can be used for either positive or negative selection in ES cell experiments. This dual capability allows the design of in-out procedures to create subtle changes in target genes by homologous recombination with the aid of this selectable minigene.

Reid, L.H.; Smithies, O.; Koller, B.H. (Univ. of North Carolina, Chapel Hill (USA)); Gregg, R.G. (Univ. of Wisconsin, Madison (USA))

1990-06-01

52

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

PubMed Central

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

2014-01-01

53

Human gene targeting favors insertions over deletions.  

PubMed

Gene targeting is a powerful technique for manipulating the human genome, but few studies have directly compared the targeting frequencies of various types of vector constructs. Here we show that similar targeting constructs are able to insert nucleotides at the homologous chromosomal target locus more efficiently than they can delete nucleotides, and combination insertion/deletion vectors appear to target at intermediate frequencies. This holds true for deletions ranging from 1 to 334 bp and insertions ranging from 1 to 1332 bp. In addition, vectors designed to inactivate the human hypoxanthine phosphoribosyltransferase gene (HPRT) by deleting nucleotides often produced rearrangements at the target locus that in many cases were due to insertions of multimerized vector constructs, effectively converting a deletion vector into an insertion vector. These findings were obtained when adeno-associated virus vectors were used to efficiently deliver single-stranded DNA targeting constructs, but the same phenomenon was also observed when transfecting linearized double-stranded plasmids. Thus human cells distinguish between deletion and insertion vectors and process their recombination intermediates differently, presumably at the heteroduplex stage, with implications for the design of gene-targeting vectors and the evolution of human genomes. PMID:18680404

Russell, David W; Hirata, Roli K

2008-09-01

54

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

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

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

55

Prognostic value of serum nicotinamide phosphoribosyltransferase in patients with bladder cancer  

PubMed Central

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

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

2014-01-01

56

Phenotype and Genotype Characterization of Adenine Phosphoribosyltransferase Deficiency  

PubMed Central

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder causing 2,8-dihydroxyadenine stones and renal failure secondary to intratubular crystalline precipitation. Little is known regarding the clinical presentation of APRT deficiency, especially in the white population. We retrospectively reviewed all 53 cases of APRT deficiency (from 43 families) identified at a single institution between 1978 and 2009. The median age at diagnosis was 36.3 years (range 0.5 to 78.0 years). In many patients, a several-year delay separated the onset of symptoms and diagnosis. Of the 40 patients from 33 families with full clinical data available, 14 (35%) had decreased renal function at diagnosis. Diagnosis occurred in six (15%) patients after reaching ESRD, with five diagnoses made at the time of disease recurrence in a renal allograft. Eight (20%) patients reached ESRD during a median follow-up of 74 months. Thirty-one families underwent APRT sequencing, which identified 54 (87%) mutant alleles on the 62 chromosomes analyzed. We identified 18 distinct mutations. A single T insertion in a splice donor site in intron 4 (IVS4 + 2insT), which produces a truncated protein, accounted for 40.3% of the mutations. We detected the IVS4 + 2insT mutation in two (0.98%) of 204 chromosomes of healthy newborns. This report, which is the largest published series of APRT deficiency to date, highlights the underdiagnosis and potential severity of this disease. Early diagnosis is crucial for initiation of effective treatment with allopurinol and for prevention of renal complications. PMID:20150536

Bollee, Guillaume; Dollinger, Cecile; Boutaud, Lucile; Guillemot, Delphine; Bensman, Albert; Harambat, Jerome; Deteix, Patrice; Daudon, Michel; Knebelmann, Bertrand

2010-01-01

57

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

SciTech Connect

The authors describe here the construction and initial characterization of a 3-fold coverage genomic library of the human haploid genome that was prepared using the bacteriophase 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 No. 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 the authors 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. 19 refs., 3 figs., 1 tab.

Shepherd, N.S.; Perogner, B.D.; Coulby, J.N.; Ackerman, S.L.; Vaidyanathan, G.; Sauer, R.H.; Balkenhol, T.C.; Sternberg, N. [Dupont Merck Pharmaceutical Co., Wilmington, DE (United States)]|[Central Research and Development Engineering Department and Service Division, Wilmington, DE (United States)

1994-03-29

58

High level glucose increases mutagenesis in human lymphoblastoid cells  

PubMed Central

Epidemiological data have suggested an increased cancer rates in diabetic patients, for which the underlying mechanism is poorly understood. We studied whether high level of glucose (HG) treatment that mimic the hyperglycemic condition in diabetes mellitus is mutagenic. Mutagenesis studies were carried out at both hypoxanthine phosphoribosyltransferase (hprt) and thymidine kinase (tk) loci. Role of p53 in HG-induced mutagenesis was also investigated by using human lymphoblastoid cell lines derived from same donor but differs in p53 statuses; TK6 has wild-type p53, NH32 has null p53, and WTK1 has mutant p53 (ile237). In addition, we studied the influence of antioxidant treatment on HG-induced mutagenesis. Mutation fractions at both loci increased significantly in all three lines at 21 and 28 days after HG treatments. At tk locus, the increase of a class of mutants with normal growth rate is mainly responsible for the overall increased mutant fraction. Compared to TK6 cells, both NH32 and WTK1 cells showed an early onset of mutagenesis. Treatment of cells with antioxidant N-acetyl-L-cysteine partially reduced HG induced mutagenesis. This study is the first to indicate that HG is able to induce gene mutation which may be one of the important mechanisms of diabetes-associated carcinogenesis. PMID:17848982

Zhang, Ying; Zhou, Junqing; Wang, Tieli; Cai, Lu

2007-01-01

59

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

SciTech Connect

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.

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

60

Effects of Hypoxanthine Substitution in Peptide Nucleic Acids Targeting KRAS2 Oncogenic mRNA Molecules: Theory and Experiment  

PubMed Central

Genetic disorders can arise from single base substitutions in a single gene. A single base substitution for wild type guanine in the twelfth codon of KRAS2 mRNA occurs frequently to initiate lung, pancreatic, and colon cancer. We have observed single base mismatch specificity in radioimaging of mutant KRAS2 mRNA in tumors in mice by in vivo hybridization with radiolabeled peptide nucleic acid (PNA) dodecamers. We hypothesized that multi-mutant specificity could be achieved with a PNA dodecamer incorporating hypoxanthine, which can form Watson-Crick basepairs with adenine, cytosine, thymine, and uracil. Using molecular dynamics simulations and free energy calculations, we show that hypoxanthine substitutions in PNAs are tolerated in KRAS2 RNA-PNA duplexes where wild type guanine is replaced by mutant uracil or adenine in RNA. To validate our predictions, we synthesized PNA dodecamers with hypoxanthine, and then measured the thermal stability of RNA-PNA duplexes. Circular dichroism thermal melting results showed that hypoxanthine-containing PNAs are more stable in duplexes where hypoxanthine-adenine and hypoxanthine-uracil base pairs are formed than single mismatch duplexes or duplexes containing hypoxanthine-guanine opposition. PMID:23972113

Sanders, Jeffrey M.; Wampole, Matthew E.; Chen, Chang-Po; Sethi, Dalip; Singh, Amrita; Dupradeau, Francois-Yves; Wang, Fan; Gray, Brian D.; Thakur, Mathew L.; Wickstrom, Eric

2013-01-01

61

Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies  

Microsoft Academic Search

Adenine phosphoribosyltransferase (APRT) deficiency leading to 2,8-dihydroxyadenine (DHA) urolithiasis has been considered a rare cause of urolithiasis and renal insufficiency. We have examined samples from 19 Japanese families with DHA lithiasis. In 79% of the families, patients only partially lacked hemolysate APRT activities, clearly contrasting with the complete deficiency in all the patients from non-Japanese families so far reported. All

Naoyuki Kamatani; Chihiro Terai; Shoko Kuroshima; Kusuki Nishioka; Kiyonobu Mikanagi

1987-01-01

62

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

Microsoft Academic Search

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 21.2eV 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 16.67eV led predominantly to the parent ion. The valence

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

2009-01-01

63

Complex changes in ecto-nucleoside 5?-triphosphate diphosphohydrolase expression in hypoxanthine phosphoribosyl transferase deficiency  

Microsoft Academic Search

Lesch-Nyhan disease is caused by a deficiency of the purine salvage enzyme, hypoxanthine phosphoribosyl transferase (HPRT). The link between HPRT deficiency and the neuropsychiatric symptoms is unknown. In rat B103 neuroblastoma cell membranes and mouse Neuro2a neuroblastoma cell membranes, nucleoside 5?-triphosphatase (NTPase) activity is substantially reduced, whereas in fibroblast membranes from HPRT knock-out mice, NTPase activity is increased. Candidate genes

Veronika Lorenz; Cibele S. Pinto; Roland Seifert

2007-01-01

64

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

E-print Network

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. ...

Pang, Bo

65

Thirdhand smoke causes DNA damage in human cells  

PubMed Central

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

Hang, Bo

2013-01-01

66

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

NASA Astrophysics Data System (ADS)

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.

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

2009-03-01

67

Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase\\/Visfatin Enzymatic Activity Identifies a New Inflammatory Pathway Linked to NAD  

Microsoft Academic Search

Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in

Nathalie Busso; Mahir Karababa; Massimo Nobile; Aline Rolaz; Frédéric van Gool; Mara Galli; Oberdan Leo; Alexander So; Thibaut de Smedt; Jacques Zimmer

2008-01-01

68

Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors.  

PubMed

A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50=2.5nM, A2780 cell proliferation IC50=9.7nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined. PMID:24279990

Zheng, Xiaozhang; Baumeister, Timm; Buckmelter, Alexandre J; Caligiuri, Maureen; Clodfelter, Karl H; Han, Bingsong; Ho, Yen-Ching; Kley, Nikolai; Lin, Jian; Reynolds, Dominic J; Sharma, Geeta; Smith, Chase C; Wang, Zhongguo; Dragovich, Peter S; Oh, Angela; Wang, Weiru; Zak, Mark; Wang, Yunli; Yuen, Po-Wai; Bair, Kenneth W

2014-01-01

69

Myocardial reperfusion injury. Role of myocardial hypoxanthine and xanthine in free radical-mediated reperfusion injury.  

PubMed

The aim of this study was to differentiate myocardial reperfusion injury from that of ischemia. We assessed the role of the myocardial adenosine 5'-triphosphate (ATP) catabolites, hypoxanthine and xanthine, generated during ischemia and the early phase of reperfusion, in reperfusion injury by modulating adenosine transport and metabolism with specific metabolic inhibitors. This was followed by intracoronary infusion of exogenous hypoxanthine and xanthine. Twenty-four dogs instrumented with minor-axis piezoelectric crystals and intraventricular pressure transducers were subjected to 30 minutes of normothermic global myocardial ischemia and 60 minutes of reperfusion. In Group 1 (n = 7), normal saline was infused into the cardiopulmonary bypass reservior before ischemia and before reperfusion. Saline solution containing 25 microM p-nitrobenzylthioinosine (NBMPR) and 100 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was infused in Group 2 (n = 10) dogs. Group 3 (n = 7) dogs were treated exactly like those in Group 2 except, at the end of the ischemic period and immediately before releasing the cross-clamp, a solution of EHNA-NBMPR containing 100 microM hypoxanthine and 100 microM xanthine was infused into the aortic root. Left ventricular performance and myocardial adenine nucleotide pool intermediates were determined before and after ischemia. ATP was depleted by about 50% (p less than 0.05 vs. preischemia) in all groups after 30 minutes of ischemia. Inosine was the major ATP catabolite (9.29 +/- 1.2 nmol/mg protein) in Group 1, while adenosine (9.91 +/- 0.7 nmol/mg protein) was the major metabolite in EHNA-NBMPR-treated dogs (Groups 2 and 3). Hypoxanthine levels were fivefold more in Group 1 compared with Groups 2 and 3 (p less than 0.05). Left ventricular performance in Group 1 decreased from 76.8 +/- 7.6 to 42.9 +/- 9.8 and 52.3 +/- 8.4 dynes/cm2 x 10(3) (p less than 0.05), while myocardial ATP decreased from 30.9 +/- 2.2 to 17.2 +/- 1.0 and 16.5 +/- 1.0 nmol/mg protein during 30 and 60 minutes of reperfusion, respectively (p less than 0.05 vs. preischemia). Ventricular function in Group 2 dogs completely recovered within 30 minutes of reperfusion, and myocardial ATP recovered to the preischemic level at 60 minutes of reperfusion. In Group 3, left ventricular performance was depressed by 39% and 30% during 30 and 60 minutes of reperfusion (p less than 0.05), respectively, and myocardial ATP did not recover during reperfusion despite a significant intramyocardial adenosine accumulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3180402

Abd-Elfattah, A S; Jessen, M E; Lekven, J; Doherty, N E; Brunsting, L A; Wechsler, A S

1988-11-01

70

Determination of xanthine in the presence of hypoxanthine by adsorptive stripping voltammetry at the mercury film electrode.  

PubMed

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

Farias, Percio Augusto Mardini; Castro, Arnaldo Aguiar

2014-01-01

71

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

PubMed Central

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

Krikavova, Radka; Hosek, Jan; Vanco, Jan; Hutyra, Jakub; Dvorak, Zdenek; Travnicek, Zdenek

2014-01-01

72

Overexpression of the Orotate Phosphoribosyl-Transferase Gene Enhances the Effect of 5Fluorouracil on Gastric Cancer Cell Lines  

Microsoft Academic Search

Objective: Orotate phosphoribosyl-transferase (OPRT) is the initial enzyme of the 5-fluorouracil (5-FU) metabolic pathway, converting 5-FU into 5-fluorouridinemonophosphate, which is the most important mechanism of 5-FU activation. We therefore investigated whether overexpression of the OPRT gene enhances sensitivity to 5-FU. Methods: An expression vector of the OPRT gene (pTARGET-OPRT) was transfected into two gastric cancer cell lines, TMK-1 and MKN-45,

Jyunnya Taomoto; Kazuhiro Yoshida; Yoshiyuki Wada; Kazuaki Tanabe; Kazuo Konishi; Hidetoshi Tahara; Masakazu Fukushima

2006-01-01

73

A haplotype of human angiotensinogen gene containing -217A increases blood pressure in transgenic mice compared with -217G.  

PubMed

The human angiotensinogen (hAGT) gene contains an A/G polymorphism at -217, and frequency of -217A allele is increased in African-American hypertensive patients. The hAGT gene has seven polymorphic sites in the 1.2-kb region of its promoter, and variant -217A almost always occurs with -532T, -793A, and -1074T, whereas variant -217G almost always occurs with -532C, -793G, and -1074G. Since allele -6A is the predominant allele in African-Americans, the AGT gene can be subdivided into two main haplotypes, -6A:-217A (AA) and -6A:-217G (AG). To understand the role of these haplotypes on hAGT gene expression and on blood pressure regulation in an in vivo situation, we have generated double transgenic mice containing human renin gene and either AA or AG haplotype of the hAGT gene using knock-in strategy at the hypoxanthine phosphoribosyltransferase locus. We show here that 1) hAGT mRNA level is increased in the liver by 60% and in the kidney by 40%; and 2) plasma AGT level is increased by approximately 40%, and plasma angiotensin II level is increased by approximately 50% in male double transgenic mice containing AA haplotype of the hAGT gene compared with the AG haplotype. In addition, systolic blood pressure is increased by 8 mmHg in transgenic mice containing the AA haplotype compared with the AG haplotype. This is the first report to show the effect of polymorphisms in the promoter of a human gene on its transcription in an in vivo situation that ultimately leads to an increase in blood pressure. PMID:18945948

Jain, Sudhir; Vinukonda, Govindaiah; Fiering, Steven N; Kumar, Ashok

2008-12-01

74

Structure-based discovery of novel amide-containing nicotinamide phosphoribosyltransferase (nampt) inhibitors.  

PubMed

Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MDCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model. PMID:23859118

Zheng, Xiaozhang; Bauer, Paul; Baumeister, Timm; Buckmelter, Alexandre J; Caligiuri, Maureen; Clodfelter, Karl H; Han, Bingsong; Ho, Yen-Ching; Kley, Nikolai; Lin, Jian; Reynolds, Dominic J; Sharma, Geeta; Smith, Chase C; Wang, Zhongguo; Dragovich, Peter S; Gunzner-Toste, Janet; Liederer, Bianca M; Ly, Justin; O'Brien, Thomas; Oh, Angela; Wang, Leslie; Wang, Weiru; Xiao, Yang; Zak, Mark; Zhao, Guiling; Yuen, Po-Wai; Bair, Kenneth W

2013-08-22

75

Cerebral Ischemia Is Exacerbated by Extracellular Nicotinamide Phosphoribosyltransferase via a Non-Enzymatic Mechanism  

PubMed Central

Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT) is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO) and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD) induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-? release in a time- and concentration-dependent fashion, while TNF-? neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-? release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-? release from glia cells, via a mechanism not related to NAMPT enzymatic activity. PMID:24392007

Han, Xue; Zhang, Xia-Yan; Xing, Qiong; Dong, Xu; Shi, Qiao-Juan; Huang, Peng; Lu, Yun-Bi; Wei, Er-Qing; Xia, Qiang; Zhang, Wei-Ping; Tang, Chun

2013-01-01

76

Radiation-quality dependent cellular response in mutation induction in normal human cells.  

PubMed

We studied cellular responses in normal human fibroblasts induced with low-dose (rate) or low-fluence irradiations of different radiation types, such as gamma rays, neutrons and high linear energy transfer (LET) heavy ions. The cells were pretreated with low-dose (rate) or low-fluence irradiations (approximately 1 mGy/7-8 h) of 137Cs gamma rays, 241Am-Be neutrons, helium, carbon and iron ions before irradiations with an X-ray challenging dose (1.5 Gy). Helium (LET = 2.3 keV/microm), carbon (LET = 13.3 keV/microm) and iron (LET = 200 keV/microm) ions were produced by the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. No difference in cell-killing effect, measured by a colony forming assay, was observed among the pretreatment with different radiation types. In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no difference in mutation frequency induced by the X-ray challenging dose between unpretreated and gamma-ray pretreated cells. In the case of the pretreatment of heavy ions, X-ray-induced mutation was around 1.8 times higher in helium-ion pretreated and 4.0 times higher in carbon-ion pretreated cells than in unpretreated cells (X-ray challenging dose alone). However, the mutation frequency in cells pretreated with iron ions was the same level as either unpretreated or gamma-ray pretreated cells. In contrast, it was reduced at 0.15 times in cells pretreated with neutrons when compared to unpretreated cells. The results show that cellular responses caused by the influence of hprt mutation induced in cells pretreated with low-dose-rate or low-fluence irradiations of different radiation types were radiation-quality dependent manner. PMID:19680011

Suzuki, Masao; Tsuruoka, Chizuru; Uchihori, Yukio; Kitamura, Hisashi; Liu, Cui Hua

2009-09-01

77

Regional gene assignment of human porphobilinogen deaminase and esterase A4 to chromosome 11q23 leads to 11qter.  

PubMed Central

The regional gene assignments for human porphobilinogen deaminase (PBGD; EC 4.3.1.8) and esterase A4 (ESA4; EC3.1.1.1) chromosome 11 have been determined with somatic cell hybridization and immunologic, electrophoretic, and cytogenetic techniques. Dimethyl sulfoxide-induced erythroid differentiation of hybrid clones derived from the fusion of tetraploid Friend murine erythroleukemia (2S MEL) cells deficient in thymidine kinase and human Lesch--Nyhan fibroblasts (HLN) deficient in hypoxanthine phosphoribosyltransferase (HPRT-; EC 2.4.2.8) were examined for expression of human PBGD, ESA4, and lactate dehydrogenase A (LDHA; EC 1.1.1.27). Human PBGD was detected by rocket immunoelectrophoresis with rabbit anti-human PBGD IgG and by isoelectric focusing. The human chromosome complement of each clone was determined by cytogenetic and enzyme marker analyses. Of the five primary 2S MEL--HLN clones examined, three were positive for human PBGD. These were subcloned to yield a total of 10 secondary, tertiary, or quaternary clones. Analyses of these subclones permitted the regional assignment of human PBGD and ESA4 to the long arm of chromosome 11. Finer regional assignment of the loci for human PBGD and ESA4 was facilitated when two 2S MEL (HPRT-)--human fibroblast (HX/11) hybrids, each containing the X chromosome--autosome translocation (der11), t(X;11)(q25-26;q23) as the only human chromosome, were examined for expression of human PBGD, ESA4, and LDHA. One clone, HX/11-2, contained the intact X/11 translocated chromosome; in the other, HX/11-3, 11p was deleted, and the human X/11 derivative was translocated onto a mouse chromosome. HX/11-2 expressed human LDHA, but HX/11-3 did not, verifying that the latter human 11/X derivative did not include 11pter leads to 11p12; PBGD and ESA4 were not detected in either hybrid. These results confirm the location of the gene for human PBGD on chromosome 11 and establish the assignment of the loci for PBGD and ESA4 in the region 11q23 leads to 11qter. Images PMID:6946513

Wang, A L; Arredondo-Vega, F X; Giampietro, P F; Smith, M; Anderson, W F; Desnick, R J

1981-01-01

78

Nicotinamide phosphoribosyltransferase inhibition reduces intraplaque CXCL1 production and associated neutrophil infiltration in atherosclerotic mice.  

PubMed

Pharmacological treatments targeting CXC chemokines and the associated neutrophil activation and recruitment into atherosclerotic plaques hold promise for treating cardiovascular disorders. Therefore, we investigated whether FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor with anti-inflammatory properties that we recently found to reduce neutrophil recruitment into the ischaemic myocardium, would exert beneficial effects in a mouse atherosclerosis model. Atherosclerotic plaque formation was induced by carotid cast implantation in ApoE-/- mice that were fed with a Western-type diet. FK866 or vehicle were administrated intraperitoneally from week 8 until week 11 of the diet. Treatment with FK866 reduced neutrophil infiltration and MMP-9 content and increased collagen levels in atherosclerotic plaques compared to vehicle. No effect on other histological parameters, including intraplaque lipids or macrophages, was observed. These findings were associated with a reduction in both systemic and intraplaque CXCL1 levels in FK866-treated mice. In vitro, FK866 did not affect MMP-9 release by neutrophils, but it strongly reduced CXCL1 production by endothelial cells which, in the in vivo model, were identified as a main CXCL1 source at the plaque level. CXCL1 synthesis inhibition by FK866 appears to reflect interference with nuclear factor-?B signalling as shown by reduced p65 nuclear levels in endothelial cells pre-treated with FK866. In conclusion, pharmacological inhibition of NAMPT activity mitigates inflammation in atherosclerotic plaques by reducing CXCL1-mediated activities on neutrophils. These results support further assessments of NAMPT inhibitors for the potential prevention of plaque vulnerability. PMID:24196571

Nencioni, Alessio; da Silva, Rafaela F; Fraga-Silva, Rodrigo A; Steffens, Sabine; Fabre, Mathias; Bauer, Inga; Caffa, Irene; Magnone, Mirko; Sociali, Giovanna; Quercioli, Alessandra; Pelli, Graziano; Lenglet, Sébastien; Galan, Katia; Burger, Fabienne; Vázquez Calvo, Sara; Bertolotto, Maria; Bruzzone, Santina; Ballestrero, Alberto; Patrone, Franco; Dallegri, Franco; Santos, Robson A; Stergiopulos, Nikolaos; Mach, François; Vuilleumier, Nicolas; Montecucco, Fabrizio

2014-02-01

79

Clonal Analysis Using Recombinant DNA Probes from the X-Chromosome1  

Microsoft Academic Search

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

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

1987-01-01

80

Ectopically Expressed CAG Repeats Cause Intranuclear Inclusions and a Progressive Late Onset Neurological Phenotype in the Mouse  

Microsoft Academic Search

The mutations responsible for several human neurodegenerative disorders are expansions of translated CAG repeats beyond a normal size range. To address the role of repeat context, we have introduced a 146-unit CAG repeat into the mouse hypoxanthine phosphoribosyltransferase gene (Hprt). Mutant mice express a form of the HPRT protein that contains a long polyglutamine repeat. These mice develop a phenotype

Jared M Ordway; Sara Tallaksen-Greene; Claire-Anne Gutekunst; Eve M Bernstein; Jamie A Cearley; Howard W Wiener; Leon S Dure; Russell Lindsey; Steven M Hersch; Richard S Jope; Roger. L Albin; Peter J Detloff

1997-01-01

81

Prototropic tautomerism and basic molecular principles of hypoxanthine mutagenicity: an exhaustive quantum-chemical analysis.  

PubMed

The molecular structures, relative stability order, and dipole moments of a complete family of 21 planar hypoxanthine (Hyp) prototropic molecular-zwitterionic tautomers including ylidic forms were computationally investigated at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum and in three different surrounding environments: continuum with a low dielectric constant (??=?4) corresponding to a hydrophobic interface of protein-nucleic acid interactions, dimethylsulfoxide (DMSO), and water. The keto-N1HN7H tautomer was established to be the global minimum in vacuum and in continuum with ??=?4, while Hyp molecule exists as a mixture of the keto-N1HN9H and keto-N1HN7H tautomers in approximately equal amounts in DMSO and in water at T?=?298.15?K. We found out that neither intramolecular tautomerization by single proton transfer in the Hyp base, nor intermolecular tautomerization by double proton transfer in the most energetically favorable Hyp·Hyp homodimer (symmetry C(2h)), stabilized by two equivalent N1H…O6 H-bonds, induces the formation of the enol tautomer (marked with an asterisk) of Hyp with cis-oriented O6H hydroxyl group relative to neighboring N1C6 bond. We first discovered a new scenario of the keto-enol tautomerization of Hyp?·?Hyp homodimer (C(2h)) via zwitterionic near-orthogonal transition state (TS), stabilized by N1?H…N1? and O6?H…N1? H-bonds, to heterodimer Hyp??·?Hyp (C(s)), stabilized by O6H…O6 and N1H…N1 H-bonds. We first showed that Hyp??·?Thy mispair (C(s)), stabilized by O6H…O4, N3H…N1, and C2H…O2 H-bonds, mimicking Watson-Crick base pairing, converts to the wobble Hyp?·?Thy base pair (C(s)), stabilized by N3H…O6 and N1H…O2 H-bonds, via high- and low-energy TSs and intermediate Hyp?·?Thy?, stabilized by O4H…O6, N1H…N3, and C2H…O2 H-bonds. The most energetically favorable TS is the zwitterionic pair Hyp??·?Thy? (C(s)), stabilized by O6?H…O4?, O6?H…N3?, N1?H…N3?, and N1?H…O2? H-bonds. The authors expressed and substantiated the hypothesis, that the keto tautomer of Hyp is a mutagenic compound, while enol tautomer Hyp? does not possess mutagenic properties. The lifetime of the nonmutagenic tautomer Hyp? exceeds by many orders the time needed to complete a round of DNA replication in the cell. For the first time purine-purine planar H-bonded mispairs containing Hyp in the anti-orientation with respect to the sugar moiety--Hyp?·?Ade(syn), Hyp?·?Gua?(syn), and Hyp?·?Gua(syn), that closely resembles the geometry of the Watson-Crick base pairs, have been suggested as the source of transversions. An influence of the surrounding environment (??=?4) on the stability of studied complexes and corresponding TSs was estimated by means of the conductor-like polarizable continuum model. Electron-topological, structural, vibrational, and energetic characterictics of all conventional and nonconventional H-bonds in the investigated structures are presented. Presented data are key to understanding elementary molecular mechanisms of mutagenic action of Hyp as a product of the adenine deamination in DNA. PMID:22962845

Brovarets', Ol'ha O; Hovorun, Dmytro M

2013-01-01

82

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

SciTech Connect

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.

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

1988-11-01

83

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

E-print Network

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 ...

Lee, Chun-Yue I.

84

Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies  

Microsoft Academic Search

2,8-Dihydroxyadenine urolithiasis associated with partial deficiencies of adenine phosphoribosyltransferase (APRT) has been found only among Japanese families. All Caucasian patients with the same lithiasis are completely deficient in this enzyme. Partially purified APRT from one of the Japanese families with the lithiasis associated with a partial deficiency of APRT had a reduced affinity for 5-phosphoribosyl-1-pyrophosphate (PRPP). In the present investigations,

S. Fujimori; I. Akaoka; K. Sakamoto; H. Yamanaka; K. Nishioka; N. Kamatani

1985-01-01

85

Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase/Visfatin Enzymatic Activity Identifies a New Inflammatory Pathway Linked to NAD  

PubMed Central

Nicotinamide phosphoribosyltransferase (NAMPT), also known as visfatin, is the rate-limiting enzyme in the salvage pathway of NAD biosynthesis from nicotinamide. Since its expression is upregulated during inflammation, NAMPT represents a novel clinical biomarker in acute lung injury, rheumatoid arthritis, and Crohn's disease. However, its role in disease progression remains unknown. We report here that NAMPT is a key player in inflammatory arthritis. Increased expression of NAMPT was confirmed in mice with collagen-induced arthritis, both in serum and in the arthritic paw. Importantly, a specific competitive inhibitor of NAMPT effectively reduced arthritis severity with comparable activity to etanercept, and decreased pro-inflammatory cytokine secretion in affected joints. Moreover, NAMPT inhibition reduced intracellular NAD concentration in inflammatory cells and circulating TNF? levels during endotoxemia in mice. In vitro pharmacological inhibition of NAMPT reduced the intracellular concentration of NAD and pro-inflammatory cytokine secretion by inflammatory cells. Thus, NAMPT links NAD metabolism to inflammatory cytokine secretion by leukocytes, and its inhibition might therefore have therapeutic efficacy in immune-mediated inflammatory disorders. PMID:18493620

Nobile, Massimo; Rolaz, Aline; Van Gool, Frederic; Galli, Mara; Leo, Oberdan; So, Alexander; De Smedt, Thibaut

2008-01-01

86

Enhancement of succinate production by metabolically engineered Escherichia coli with co-expression of nicotinic acid phosphoribosyltransferase and pyruvate carboxylase.  

PubMed

Escherichia coli BA002, in which the ldhA and pflB genes are deleted, cannot utilize glucose anaerobically due to the inability to regenerate NAD(+). To restore glucose utilization, overexpression of nicotinic acid phosphoribosyltransferase (NAPRTase) encoded by the pncB gene, a rate-limiting enzyme of NAD(H) synthesis pathway, resulted in a significant increase in cell mass and succinate production under anaerobic conditions. However, a high concentration of pyruvate accumulated. Thus, co-expression of NAPRTase and the heterologous pyruvate carboxylase (PYC) of Lactococcus lactis subsp. cremoris NZ9000 in recombinant E. coli BA016 was investigated. The total concentration of NAD(H) was 9.8-fold higher in BA016 than in BA002, and the NADH/NAD(+) ratio decreased from 0.60 to 0.04. Under anaerobic conditions, BA016 consumed 17.50 g l(-1) glucose and produced 14.08 g l(-1) succinate with a small quantity of pyruvate. Furthermore, when the reducing agent dithiothreitol or reduced carbon source sorbitol was added, the cell growth and carbon source consumption rate of BA016 was reasonably enhanced and succinate productivity increased. PMID:23740313

Ma, Jiangfeng; Gou, Dongmei; Liang, Liya; Liu, Rongming; Chen, Xu; Zhang, Changqing; Zhang, Jiuhua; Chen, Kequan; Jiang, Min

2013-08-01

87

Substrate Inhibition of Uracil Phosphoribosyltransferase by Uracil Can Account for the Uracil Growth Sensitivity of Leishmania donovani Pyrimidine Auxotrophs*  

PubMed Central

The pathogenic protozoan parasite Leishmania donovani is capable of both de novo pyrimidine biosynthesis and salvage of pyrimidines from the host milieu. Genetic analysis has authenticated L. donovani uracil phosphoribosyltransferase (LdUPRT), an enzyme not found in mammalian cells, as the focal enzyme of pyrimidine salvage because all exogenous pyrimidines that can satisfy the requirement of the parasite for pyrimidine nucleotides are funneled to uracil and then phosphoribosylated to UMP in the parasite by LdUPRT. To characterize this unique parasite enzyme, LdUPRT was expressed in Escherichia coli, and the recombinant enzyme was purified to homogeneity. Kinetic analysis revealed apparent Km values of 20 and 99 ?m for the natural substrates uracil and phosphoribosylpyrophosphate, respectively, as well as apparent Km values 6 and 7 ?m for the pyrimidine analogs 5-fluorouracil and 4-thiouracil, respectively. Size exclusion chromatography revealed the native LdUPRT to be tetrameric and retained partial structure and activity in high concentrations of urea. L. donovani mutants deficient in de novo pyrimidine biosynthesis, which require functional LdUPRT for growth, are hypersensitive to high concentrations of uracil, 5-fluorouracil, and 4-thiouracil in the growth medium. This hypersensitivity can be explained by the observation that LdUPRT is substrate-inhibited by uracil and 4-thiouracil, but 5-fluorouracil toxicity transpires via an alternative mechanism. This substrate inhibition of LdUPRT provides a protective mechanism for the parasite by facilitating purine and pyrimidine nucleotide pool balance and by sparing phosphoribosylpyrophosphate for consumption by the nutritionally indispensable purine salvage process. PMID:23986453

Soysa, Radika; Wilson, Zachary N.; Elferich, Johannes; Forquer, Isaac; Shinde, Ujwal; Riscoe, Michael K.; Yates, Phillip A.; Ullman, Buddy

2013-01-01

88

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

PubMed Central

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

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

2014-01-01

89

Sensitivity of somatic mutations in human umbilical cord blood to maternal environments.  

PubMed

To assess the potential effect of maternal environments on human embryonic/fetal somatic mutation, we measured the frequencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (Mf), and glycophorin A (GPA) variant erythrocytes (Vf) of both allele-loss (phi/N) and allele-loss-and-duplication (N/N) phenotypes in umbilical cord blood. The mean hprt Mf (1.40 +/- 1.11 x 10(-6), N = 66) and GPA Vf (phi/N 4.0 +/- 2.2 x 10(-6), N = 114; N/N 2.7 +/- 2.0 x 10(-6), N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt Mf was significantly higher than that of a published study of newborn cord blood samples from a geographically distant population (0.64 +/- 0.41 x 10(-6), N = 45, P < 0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt Mf (0.70 +/- 0.49 x 10(-6)) of this selected population was consistent with the published report and significantly lower than that of our initial population (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These results indicate that there is an environmental effect related to maternal socioeconomic status on the frequency of embryonic/fetal somatic mutations. Molecular analyses of hprt mutants from this cohort with elevated Mf revealed a significant decrease in the relative contribution of gross structural mutations to the overall Mf (25 of 38, 66% vs. 34 of 41, 83%, P = 0.024, chi 2 test), suggesting that the higher Mf resulted from an elevated level of "point" mutations. No individual maternal demographic or environmental factor was identified as contributing more significantly than other any factor to the observed variability in hprt Mf or GPA Vf. PMID:7588645

Manchester, D K; Nicklas, J A; O'Neill, J P; Lippert, M J; Grant, S G; Langlois, R G; Moore, D H; Jensen, R H; Albertini, R J; Bigbee, W L

1995-01-01

90

Expression of catalytic domains of human UMP synthase in uridine auxotrophic bacteria  

Microsoft Academic Search

Orotate phosphoribosyltransferase (OPRT) and orotidine-5'-monophosphate decarboxylase (ODC), which catalyze the last two steps in de novo UMP biosynthesis, are two distinct monofunctional proteins in bacteria and lower eukaryotes. In mammals, OPRT and ODC activities are contained in a single bifunctional protein labeled UMP synthase. The human UMP synthase cDNA was separated into the predicted OPRT and ODC domains using polymerase

Ti Lin; D. Parker Suttle

1993-01-01

91

Human hybrid hybridoma  

SciTech Connect

Hybrid hybridomas are obtained by fusion of two cells, each producing its own antibody. Several authors have reported the construction of murine hybrid hybridomas with the aim to obtain bispecific monoclonal antibodies. The authors have investigated, in a model system, the feasibility of constructing a human hybrid hybridoma. They fused two monoclonal cell lines: an ouabain-sensitive and azaserine/hypoxanthine-resistant Epstein-Barr virus-transformed human cell line that produces an IgG1kappa antibody directed against tetanus toxiod and an azaserine/hypoxanthine-sensitive and ouabain-resistant human-mouse xenohybrid cell line that produces a human IgG1lambda antibody directed against hepatitis-B surface antigen. Hybrid hybridoma cells were selected in culture medium containing azaserine/hypoxanthine and ouabain. The hybrid nature of the secreted antibodies was analyzed by means of two antigen-specific immunoassay. The results show that it is possible, with the combined use of transformation and xenohybridization techniques, to construct human hybrid hybridomas that produce bispecific antibodies. Bispecific antibodies activity was measured by means of two radioimmunoassays.

Tiebout, R.F.; van Boxtel-Oosterhof, F.; Stricker, E.A.M.; Zeijlemaker, W.P.

1987-11-15

92

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

PubMed Central

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

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

2014-01-01

93

Quantifaction of mutagens at the Na/sup +/-K/sup +/-ATPase and hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene loci in Chinese hamster ovary cells  

SciTech Connect

The Chinese hamster ovary (CHO) cell/hypoxanthine guanine phosphoribosyl transferase (HGPRT) mutagen assay developed by Hsie et al., was simplified by culturing the cells as unattached cultures, and also modified to include mutation at the Na/sup +/-K/sup +/ ATPase (ouabain resistance) gene locus. The cost and time involved were decreased by culturing the CHO cells unattached on nontissue culture plates during the expression period. The inclusion of a second gene locus ensures that mutagenicities observed were not due to the peculiar properties of a specific gene locus. These procedures are now used in our laboratory for routine testing of environmental chemicals and complex mixtures.

Li, A.P.

1982-01-01

94

Adenine Phosphoribosyltransferase (APRT) Deficiency  

MedlinePLUS

... reddish-brown diaper stains. The 2,8-dihydroxyadenine crystals should be easily detected by urine microscopy. The ... enzyme activity. Furthermore, analysis of 2,8-DHA crystals and stone material may confirm the diagnosis. What ...

95

Bilirubin UDP-glucuronosyltransferase 1A1 (UGT1A1) gene promoter polymorphisms and HPRT, glycophorin A, and micronuclei mutant frequencies in human blood.  

PubMed

A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 (UGT1A1) gene. 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- and 8-TA displayed marginally lower GPA_NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes ( [Formula: see text] ). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7- and 8-TA) were associated with modestly increased HPRT mutation frequency ( [Formula: see text] ), 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- and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7- and 8-TA were associated with increased GPA_NØ mutant frequency relative to 5/5, 5/6, 6/6 genotypes ( [Formula: see text] ). 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. PMID:15099818

Grant, Delores J; Hall, Ingrid J; Eastmond, David A; Jones, Irene M; Bell, Douglas A

2004-05-01

96

Xanthine oxidase inhibits growth of Plasmodium falciparum in human erythrocytes in vitro.  

PubMed Central

Malaria parasites, unable to synthesize purine de novo, use host-derived hypoxanthine preferentially as purine source. In a previous study (1990. J. Biol. Chem. 265:6562-6568), we noted that xanthine oxidase rapidly and completely depleted hypoxanthine in human erythrocytes, not by crossing the erythrocyte membrane, but rather by creating a concentration gradient which facilitated hypoxanthine efflux. We therefore investigated the ability of xanthine oxidase to inhibit growth of FCR-3, a chloroquine-resistant strain of Plasmodium falciparum in human erythrocytes in vitro. Parasites were cultured in human group O+ erythrocytes in medium supplemented, as required, with xanthine oxidase or chloroquine. Parasite viability was assessed by uptake of radiolabeled glycine and adenosine triphosphate-derived purine into protein and nucleic acid, respectively, by nucleic acid accumulation, by L-lactate production, and by microscopic appearance. On average, a 90% inhibition of growth was observed after 72 h of incubation in 20 mU/ml xanthine oxidase. Inhibition was notably greater than that exerted by 10(-7) M chloroquine (less than 10%) over a comparable period. The IC50 for xanthine oxidase was estimated at 0.2 mU/ml, compared to 1.5 x 10(-7) M for chloroquine. Inhibition was completely reversed by excess hypoxanthine, but was unaffected by oxygen radical scavengers, including superoxide dismutase and catalase. The data confirms that a supply of host-derived hypoxanthine is critical for nucleic acid synthesis in P. falciparum, and that depletion of erythrocyte hypoxanthine pools of chloroquine-resistant malaria infection in humans. of chloroquine-resistant malaria infection in humans. Images PMID:1752946

Berman, P A; Human, L; Freese, J A

1991-01-01

97

A theoretical study of structures and electron affinities of radical anions of guanine-cytosine, adenine-thymine, and hypoxanthine-cytosine base pairs.  

PubMed

Adiabatic electron affinities (AEA) and structural perturbations due to addition of an excess electron to each of the neutral guanine-cytosine (G-C), adenine-thymine (A-T), and hypoxanthine-cytosine (HX-C) base pairs were studied using the self-consistent charge, density functional tight-binding (SCC-DFTB-D) method, augmented by the empirical London dispersion energy term. Performance of the SCC-DFTB-D method was examined by comparing the calculated results using it with those obtained from experiment as well as ab initio and other different density functional theoretical studies. An excellent agreement between the SCC-DFTB-D results and those obtained by the other calculations regarding the structural modifications, hydrogen bonding, and dissociation energies of the neutral and radical anion base pairs was found. It is shown that adiabatic electron affinity can be better predicted by considering reaction enthalpies of formation of the respective neutral and anionic base pairs from their respective molecular components instead of taking the difference between their total energies. The calculated AEAs of the base pairs were compared with those obtained by the bracketing method from Schaefer and coworkers, where a satisfactory agreement was found. It shows applicability of the SCC-DFTB-D method to study charged DNA models at a highly economical computational cost. PMID:15067680

Kumar, Anil; Knapp-Mohammady, Michaela; Mishra, P C; Suhai, Sándor

2004-06-01

98

Reinvestigation of the molecular influence of hypoxanthine on the DNA cleavage efficiency of restriction endonucleases BglII, EcoRI and BamHI.  

PubMed

Hypoxanthine (Hyp), a deaminated base of adenine (Ade), can be employed as a good probe molecule to reveal the significance of the minor groove of guanine (Gua) in biomolecular interactions because Hyp possesses a similar structure to Gua lacking its 2-amino group. In this study, we examined cleavage efficiencies of restriction endonuclease enzymes on DNA substrates with Hyp in their recognition sequences. As a substrate for BglII, EcoRI and BamHI, 24-mer DNA oligomer with Hyp (in place of Gua) was prepared together with its complementary sequences with cytosine (Cyt) or thymine (Thy) as the counter base. At 37 degrees C incubation for 1 h, BglII and EcoRI showed higher DNA cleavage reactivity on Hyp-containing DNA substrates than on normal ones, whereas BamHI showed lower values on Hyp-containing substrates. Such high cleavage performance of BglII and EcoRI on Hyp-containing DNA substrates is in contrast to the results obtained 20 years ago, in which short DNA substrates (8- or 10-mer) and low reaction temperatures (15-20 degrees C) were employed. These new results suggest that the lack of the exocyclic 2-amino group of Gua could contribute to enhanced recognition access of BglII and EcoRI to DNA substrates. PMID:19364803

Doi, Akihiro; Pack, Seung Pil; Kodaki, Tsutomu; Makino, Keisuke

2009-08-01

99

Detection of an amino acid substitution in the mutant enzyme for a special type of adenine phosphoribosyltransferase (APRT) deficiency by sequence-specific protein cleavage.  

PubMed Central

Generally, if mutant and normal proteins have similar molecular weights and electric charges, they cannot easily be distinguished from one another. We have developed a unique method by which a mutant enzyme of adenine phosphoribosyltransferase (APRT) can easily be distinguished from normal enzyme with nearly identical molecular weight and electric charge. DNA sequencing data have suggested that in this special type of disease (Japanese-type APRT deficiency) there is an amino acid substitution from Met to Thr at position 136 of APRT. Since normal APRT has only one Met residue, the Japanese-type mutant APRT should be a methionine-free protein. Using both an amino acid sequence-specific antiserum against APRT, and specific cleavage of peptide at the methionine residue with BrCN, we could distinguish between normal and mutant proteins. Thus, normal but not mutant APRT was cleaved with BrCN, indicating that the mutant APRT is a methionine-free protein. All tested patients with the Japanese-type APRT deficiency were found to synthesize exclusively methionine-free APRT. Usefulness of this method is not restricted to a single family, as 79% of all the patients with this disease among Japanese, and more than half of all the patients with this disease reported in the world, are likely to have this unique mutation. Thus, not only sequence-specific cleavage of DNA with restriction endonucleases but also that of protein with a chemical agent has been shown to be sometimes useful for the diagnosis and analysis of a genetic disease by careful examination of normal and mutant amino acid sequences. Images Figure 2 Figure 3 Figure 4 PMID:2502918

Kamatani, N; Kuroshima, S; Terai, C; Hidaka, Y; Palella, T D; Nishioka, K

1989-01-01

100

Adenovirus-mediated Transduction of Escherichia coli Uracil Phosphoribosyltransferase Gene Sensitizes Cancer Cells to Low Concentrations of 5Fluorouracil1  

Microsoft Academic Search

fluorouracil (5-FU), although a widely used chemotherapuetic agent, has a limited effect in the treatment of human solid tumors due to their resistance to the cytotoxic effects of 5-FU. Escherichia coli uracil phos- phoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that cata lyzes the synthesis of UMP from uracil and 5-phosphoribosyl-a-l-diphos- phate. The present study demonstrates that adenovirus-mediated transduction of

Fumihiko Kanai; Takayuki Kawakami; Hirofumi Hamada; Akiko Sudata; Yoko Yoshida; Torao Tanaka; Makoto Ohashi; Keisuke Tateishi; Yasushi Shiratori; Masao Ornata

1998-01-01

101

Determination of adenine nucleotides and their metabolites in human saliva.  

PubMed

The profile and normal concentrations of nucleotide metabolites in human saliva and reproducibility of these determinations were analyzed. Samples of human saliva collected from healthy individuals at weekly intervals, were deproteinized and analysed for the content of adenine nucleotides and their metabolites by reversed-phase HPLC. Initial ATP, hypoxanthine and uric acid concentrations were 0.52 +/- 0.15 microM, 1.91 +/- 0.37 microM and 184 +/- 22 microM respectively. A substantial individual variation persisted within 3 weeks of sampling excepted hypoxanthine which showed some unrelated variations. Determination of nucleotides and their catabolites in saliva due to its simplicity and reproducibility, may be of clinical value in diagnosis of local or systemic disorders. PMID:11310987

Kocha?ska, B; Smole?ski, R T; Knap, N

2000-01-01

102

Human somatic mutation assays as biomarkers of carcinogenesis  

SciTech Connect

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.

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

103

The properdin structural locus (Pfc) lies close to the locus for tissue inhibitor of metallothionine proteases (Timp) on the mouse X chromosome.  

PubMed

We have confirmed the assignment of the structural locus of the complement factor properdin (Pfc) to the mouse X chromosome and mapped it between monoamine oxidase-A (Mao-a) and hypoxanthine phosphoribosyltransferase (Hprt) using a Mus spretus x Mus musculus interspecific backcross of 108 animals. The structural locus for murine tissue inhibitor of metallothionine proteases (Timp) could not be separated from properdin in a panel of 18 recombinant animals. By minimizing the number of double recombinants the following gene order was obtained: Otc-Mao-a-(Pfc, Timp)-Hprt-Cf-9. The implications for comparative mapping of human and mouse X chromosomes are discussed. PMID:1916808

Laval, S H; Chen, Z Y; Boyd, Y

1991-08-01

104

Mutagenicity of stereochemical configurations of 1,3-butadiene epoxy metabolites in human cells.  

PubMed

The mutagenic and carcinogenic effects of 1,3-butadiene (BD*) are related to its bioactivation to several DNA-reactive metabolites, including 1,2-epoxy-3-butene (BDO), 1,2,3,4-diepoxybutane (BDO2), and 1,2-dihydroxy-3,4-epoxybutane (BDO-diol). Accumulated evidence indicates that stereochemical configurations of BD metabolites may play a role in the mutagenic and carcinogenic action of BD. The objective of this study was to evaluate the cytotoxicity and mutagenicity of each stereoisomer of major BD metabolites in human cells. For this purpose, nine stereochemical forms of BDO, BDO2, and BDO-diol were synthesized. TK6 cells, a human lymphoblastoid cell line, were exposed to each stereoisomer. Cytotoxicity was measured by comparing cloning efficiencies (CEs) in chemical-exposed cells versus those in control cells. Based on the results of cytotoxicity tests, TK6 cells were exposed to 0; 2, 4, or 6 pM of each form of BDO2, or to 0, 200, 400, or 600 pMof each form of BDO for 24 hours to determine the mutagenic efficiencies. The exposure concentrations for BDO-diol ranged from 5 to 1000 pM. The mutagenicity was measured by determining, in a lymphocyte cloning assay, the mutant frequencies (Mfs) in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK) genes. HPRT mutants collected from cells exposed to the three forms of BDO2 were analyzed by polymerase chain reaction (PCR) to characterize large genetic alterations. All three stereoisomers of BDO2 [(2R,3R)-BDO2, (2S,3S)-BDO2, and meso-BDO2] caused increased HPRT and TK Mfs compared with the concurrent control samples, with P values ranged from 0.05 to 0.001. There were no significant differences in cytotoxicity or mutagenicity among the three isomers of BDO2. Molecular analysis ofHPRTmutants revealed similar distributions of deletion mutations caused by the three isomers of BDO2. There were also no statistical differences in mutagenic efficiencies between the two isomers of BDO [(2R)-BDO and (2S)-BDO] in TK6 cells. These results were consistent with the in vivo finding that there was little difference in the mutagenic efficiencies of (+)-BDO2 versus meso-BDO2 in rodents. Thus, in terms of mutagenic potency, there was no evidence that stereochemical configurations of BDO and BDO2 play a significant role in the mutagenicity and carcinogenicity of BD. The most significant results of this study were the marked differences in cytotoxicity and mutagenicity among the four stereoisomers of BDO-diol [(2R,3R)-BDO-diol, (2R,3S)-BDO-diol, (2S,3R)-BDO-diol, and (2S,3S)-BDO-diol]. (2R,3S)-BDO-diol was at least 30-fold more cytotoxic and mutagenic than the other three forms of BDO-diol. This was consistent with the finding that 75% of the adduct N7-(2,3,4-trihydroxybutyl)guanine (THB-Gua) originated from (2R,3S)-BDO-diol in the lungs of mice exposed to BD. The mutagenic potency of (2R,3S)-BDO-diol was much closer to that of BDO2 than previously demonstrated in experiments in which stereochemistry was not considered. The current study demonstrated that the mutagenic potency of (2R,3S)-BDO-diol was only 5-to-l0-fold less than the average equimolar effect of BDO2 stereoisomers in the HPRT and TK genes, and was 10-to-20-fold greater than the average equimolar effect of BDO stereoisomers in the HPRT and TKgenes. Previous DNA and hemoglobin adduct data demonstrated that BDO-diol is the dominant BD metabolite available to react with macromolecules in vivo after BD exposure (Pérez et al. 1997; Swenberg et al. 2001). Thus, the differences in BD carcinogenesis among rodent species may be significantly accounted for by the stereochemistry-dependent distributions of BDO-diol metabolites and BDO-diol-DNA adducts, and by the mutagenic efficiencies of BDO-diol in mice and rats. PMID:20853577

Meng, Ryan Q; Hackfeld, Linda C; Hedge, Richard P; Wisse, Lynne A; Redetzke, Diana L; Walker, Vernon E

2010-06-01

105

Monochromosomal hybrids for the analysis of the human genome  

SciTech Connect

In this research project the authors proposed to develop rodent/human hybrid cell lines each containing a single different human chromosome. The human chromosomes will be marked with Ecogpt and stably maintained by selection in the hybrid cells. The experimental approach to produce the proposed cell lines involve the following: they will first transfer a cloned selectable marker, Ecogpt (an E. coli gene for xanthine-guanine phosphoribosyltransferase: XGPRT) to normal diploid human cells using a retroviral vector. The transferred gene will integrate at random into multiple sites in the recipient cell genome. Clonal cell lines from independent transgenotes will each carry the selectable marker integrated into a different site and perhaps a different chromosome. The chromosome carrying the selectable marker will then be transferred further to mouse cells by microcell fusion. In addition they also use directed integration of Ecogpt into the chromosome present in rodent cells, otherwise not marked with a selectable marker. This allows them to complete the bank of proposed cell line. The human chromosome, since it will be marked with a selectable marker, can be transferred to any other cell line of interest for complementation analysis. Clones of each cell line, containing varying size segments of the same chromosome produced by selection for the retention or loss of the selectable marker following x-irradiation or by metaphase chromosome transfer method will facilitate physical mapping and determination of gene order on a chromosome. 1 fig.

Athwal, R.S.

1990-01-01

106

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

SciTech Connect

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.

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

2006-01-01

107

Expression and regulation of nampt in human islets.  

PubMed

Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the mammalian NAD+ biosynthesis of a salvage pathway and exists in 2 known forms, intracellular Nampt (iNampt) and a secreted form, extracellular Nampt (eNampt). eNampt can generate an intermediate product, nicotinamide mononucleotide (NMN), which has been reported to support insulin secretion in pancreatic islets. Nampt has been reported to be expressed in the pancreas but islet specific expression has not been adequately defined. The aim of this study was to characterize Nampt expression, secretion and regulation by glucose in human islets. Gene and protein expression of Nampt was assessed in human pancreatic tissue and isolated islets by qRT-PCR and immunofluorescence/confocal imaging respectively. Variable amounts of Nampt mRNA were detected in pancreatic tissue and isolated islets. Immunofluorescence staining for Nampt was found in the exocrine and endocrine tissue of fetal pancreas. However, in adulthood, Nampt expression was localized predominantly in beta cells. Isolated human islets secreted increasing amounts of eNampt in response to high glucose (20 mM) in a static glucose-stimulated insulin secretion assay (GSIS). In addition to an increase in eNampt secretion, exposure to 20 mM glucose also increased Nampt mRNA levels but not protein content. The secretion of eNampt was attenuated by the addition of membrane depolarization inhibitors, diazoxide and nifedipine. Islet-secreted eNampt showed enzymatic activity in a reaction with increasing production of NAD+/NADH over time. In summary, we show that Nampt is expressed in both exocrine and endocrine tissue early in life but in adulthood expression is localized to endocrine tissue. Enzymatically active eNampt is secreted by human islets, is regulated by glucose and requires membrane depolarization. PMID:23536823

Kover, Karen; Tong, Pei Ying; Watkins, Dara; Clements, Mark; Stehno-Bittel, Lisa; Novikova, Lesya; Bittel, Doug; Kibiryeva, Nataliya; Stuhlsatz, Jacob; Yan, Yun; Ye, Shui Qing; Moore, Wayne V

2013-01-01

108

Delineation of the motor disorder of Lesch-Nyhan disease  

Microsoft Academic Search

Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study

H. A. Jinnah; Jasper E. Visser; James C. Harris; Alfonso Verdu; Laura Larovere; I. Ceballos-Picot; P. Gonzalez-Alegre; V. Neychev; R. J. Torres; O. Dulac; I. Desguerre; D. J. Schretlen; K. L. Robey; G. Barabas; B. R. Bloem; W. L. Nyhan; R. Kremer; G. E. Eddey; J. G. Puig; S. G. Reich

2006-01-01

109

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

Microsoft Academic Search

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

István Pályi; Judit Bence; Károly Szikla; Lehel Hullán

1989-01-01

110

Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells  

Microsoft Academic Search

Cultured P388\\/VCR mouse lymphoma cells resistant to vincristine (VCR) and 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-). The hybrid cells expressed multidrug resistance (MDR), i.e., resistance to VCR and cross-resistance to Adriamycin (ADM) and actinomycin

István Pályi; Gizella Turi; Lehel Hullán; Károly Szikla; Mihály Bak

1994-01-01

111

Dominant expression of multidrug resistance in intraspecific murine lymphoma hybrid cells  

Microsoft Academic Search

Cultured P388\\/VCR mouse lymphoma cells resistant to vincristine (VCR) and 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 –). The hybrid cells expressed multidrug resistance (MDR), i.?e., resistance to VCR and cross-resistance to Adriamycin (ADM)

István Pályi; Gizella Turi; Lehel Hullán; Károly Szikla; Mihály Bak

1994-01-01

112

Molecular Structure of 6-Mercaptopurine  

NSDL National Science Digital Library

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.

2002-09-12

113

Isolation of human-mouse somatic cell hybrids producing human prolactin: dominant expression of hormone secretion and regulation.  

PubMed

Human PRL (hPRL)-secreting adenoma cells obtained at hypophysectomy were fused with a mutant mouse fibroblast line (LMTK-) which is aminopterin sensitive due to a deficiency in the enzyme thymidine kinase. After fusion with polyethylene glycol, cells containing nuclear material from the two parental lines (heterokaryons) were selected in medium containing hypoxanthine, aminopterin, and thymidine, and resultant clones were screened for hPRL secretion. Functional human X mouse somatic cell hybrid clones secreting hPRL were isolated in order to study hPRL gene expression and regulation. Positive hybrid clones were subcultured and have sustained hPRL secretion. The hybrid nature of the cells was confirmed by fibroblastic morphology resembling the mouse parental cell, mixed karyotype of mouse and human chromosomes, and mixed isozyme banding pattern for human and mouse glucose-6-phosphate dehydrogenase and malic enzyme. Specific expression of the hPRL gene was demonstrated by the presence of electron microscopic secretory granules (650-800 nm), positive immunoperoxidase staining using anti-hPRL serum, and sustained secretion of immunoreactive hPRL, which comigrated with [125I] hPRL standard on Sephadex chromatography. Hormonal modulation of hPRL gene expression by TRH was dominantly expressed in the hybrid cell. Human chromosome 6 was identified in hybrid cells secreting hPRL, and the cells expressed human malic enzyme, a marker for this chromosome, thus confirming the chromosome assignment of the hPRL gene. The results show that functional replicating hybrids secreting hPRL can be isolated. The technique provides a useful in vitro model for the study of hPRL gene expression and modulation. PMID:6404919

Melmed, S

1983-06-01

114

Radiation-induced HPRT mutations resulting from misrejoined DNA double-strand breaks.  

PubMed

DNA double-strand breaks (DSBs) are the most severe lesions induced by ionizing radiation, and unrejoined or misrejoined DSBs can lead to cell lethality, mutations and the initiation of tumorigenesis. We have investigated X-ray- and alpha-particle-induced mutations that inactivate the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene in human bladder carcinoma cells and in hTERT-immortalized human fibroblasts. Fifty to 80% of the mutants analyzed exhibited partial or total deletions of the 9 exons of the HPRT locus. The remaining mutants retained unaltered PCR products of all 9 exons but often displayed a failure to amplify the HPRT cDNA. Hybridization analysis of a 2-Mbp NotI fragment spanning the HPRT gene with a probe 200 kbp distal to the HPRT locus indicated altered fragment sizes in most of the mutants with a wild-type PCR pattern. These mutants likely contain breakpoints for genomic rearrangements in the intronic sequences of the HPRT gene that allow the amplification of the exons but prevent HPRT cDNA amplification. Additionally, mutants exhibiting partial and total deletions of the HPRT exons also frequently displayed altered NotI fragments. Interestingly, all mutations were very rarely associated with interchromosomal exchanges analyzed by FISH. Collectively, our data suggest that intrachromosomal genomic rearrangements on the Mbp scale represent the prevailing type of radiation-induced HPRT mutations. PMID:18494542

Rothkamm, Kai; Gunasekara, Kut; Warda, Salam A; Krempler, Andrea; Löbrich, Markus

2008-06-01

115

Characterization of a human antigen specific helper factor  

SciTech Connect

While antigen (Ag) specific helper factors have been characterized in mice, similar molecules have not been identified in humans. To characterize human antigen specific helper molecules, an IL-2 dependent tetanus toxoid (T.T.) reactive T cell line was fused with a 6-thioguanine resistant CEM line, and hybrids selected in medium containing hypoxanthine and azaserine. Hybrids were screened by culturing the cells with /sup 35/S-Met then reacting the supernatants with T.T. or hepatitis vaccine immobilized on nitrocellulose. One hybrid, TT6BA-O, was identified which secreted a Met-containing molecule which bound T.T. but not hepatitis vaccine. Supernatants from TT6BA-O, but not the parent CEM line, when added to autologous peripheral blood mononuclear cells (PBMC's) stimulated secretion of T.T. specific antibodies (Abs). Specificity controls demonstrated that TT6BA-O supernatant did not induce antibodies to diphtheria toxoid, hepatitis vaccine or pneumococcal polysaccharide, and total immunoglobulin (lg) synthesis was minimally increased. In contrast, pokeweed mitogen stimulated significant lg synthesis as well as Ab's to pneumococcal polysaccharide and T.T. TT6BA-O supernatant induced anti-T.T.Ab's in autologous PBMC's but not PBMC's from 3 unrelated donors, suggesting that the activity of the helper factor is restricted, possibly by the MHC. The molecular weight of the helper factor was estimated at 100,000-150,000 by Sephacryl S-300 chromatography. Finally, the helper factor could be demonstrated to bind and elute from sephorose-immobilized T.T. and anti-DR antisera, but not anti-lg antisera or the T40/25 monoclonal antibody, which binds a nonpolymorphic determinant on the human T cell receptor. These results demonstrate that human Ag specific helper factors exist, bind antigen and bear class II MHC determinants.

Richardson, B.

1986-03-01

116

A method to generate microcells from human lymphoblasts for use in microcell mediated chromosome transfer.  

PubMed

A method is described to generate microcells from human lymphoblasts for use in microcell-mediated chromosome transfer (MMCT). Micronuclei were induced in cells from a human lymphoblastic cell line by prolonged colcemid treatment, and were separated from these lymphoblasts by: attaching the cells to Concanavalin A coated plastic slides designed for enucleation, and centrifuging the slides in medium containing cytochalasin B. Microcells of less than 3 microns in diameter were fused with thymidine kinase negative mouse fibroblasts (LMTK-). HAT medium (hypoxanthine, aminopterin, and thymidine) was used to select microcell hybrids expressing thymidine kinase activity. Positive clones were isolated and Q-banded for chromosome analysis. Unlike previous methods, this procedure permits microcells to be easily generated from lymphoid cells. The methodology of enucleation of microcells may be extended to a variety of other donor cell types which can be micronucleated but which do not adhere tightly to enucleation slides and do not exhibit extrusion subdivision. This feature makes our methodology particularly useful for constructing a library of hybrid clones containing one or a few human chromosomes. PMID:3533893

Devore-Carter, D L; Pietrzak, E; Kakati, S

1986-10-01

117

Epstein-barr virus shuttle vector for stable episomal replication of cDNA expression libraries in human cells  

SciTech Connect

Efficient transfection and expression of cDNA libraries in human cells has been achieved with an Epstein-Barr virus-based subcloning vector (EBO-pcD). The plasmid vector contains a resistance marker for hygromcying B to permit selection for transformed cells. The Epstein-Barr virus origin for plasmid replication (oriP) and the Epstein-Barr virus nuclear antigen gene have also been incorporated into the vector to ensure that the plasmids are maintained stably and extrachromosomally. Human lymphoblastodi cells can be stably transformed at high efficiency (10 to 15%) by such plasmids, thereby permitting the ready isolation of 10/sup 6/ to 10/sup 7/ independent transformants. Consequently, entire high-complexity EBO-pcD expression libraries can be introduced into these cells. Furthermore, since EBP-pcD plasmids are maintained as episomes at two to eight copies per cell, intact cDNA clones can be readily isolated from transformants and recovered by propagation in Escherichia coli. By using such vectors, human cells have been stably transformed with EBO-pcD-hprt to express hypoxanthing-guanine phosphoribosyltransferase and with EBO-pcD-Leu-2 to express the human T-cell surface marker Leu-2. Reconstruction experiments with mixtures of EBO-pcD plasmids demonstrated that one clone of EBO-pcD-hprt per 10/sup 6/ total clones or one clone of EBO-pcD-Leu-2 per 2 x 10/sup 4/ total clones can be recovered intact from the transformed cells. The ability to directly select for expression of very rare EBO-pcD clones and to then recover these episomes should make it possible to clone certain genes where hybridization and immunological screening methods are not applicable but where a phenotype can be scored or selected in human cell lines.

Margolskee, R.F.; Kavathas, P.; Berg, P.

1988-07-01

118

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

PubMed

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

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

119

Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer  

PubMed Central

Infection-driven inflammation has been implicated in the pathogenesis of ~15–20% of human tumors. Expression of microRNA-155 (miR-155) is elevated during innate immune response and autoimmune disorders as well as in various malignancies. However, the molecular mechanisms providing miR-155 with its oncogenic properties remain unclear. We examined the effects of miR-155 overexpression and proinflammatory environment on the frequency of spontaneous hypoxanthine phosphoribosyltransferase (HPRT) mutations that can be detected based on the resistance to 6-thioguanine. Both miR-155 overexpression and inflammatory environment increased the frequency of HPRT mutations and down-regulated WEE1 (WEE1 homolog-S. pombe), a kinase that blocks cell-cycle progression. The increased frequency of HPRT mutation was only modestly attributable to defects in mismatch repair machinery. This result suggests that miR-155 enhances the mutation rate by simultaneously targeting different genes that suppress mutations and decreasing the efficiency of DNA safeguard mechanisms by targeting of cell-cycle regulators such as WEE1. By simultaneously targeting tumor suppressor genes and inducing a mutator phenotype, miR-155 may allow the selection of gene alterations required for tumor development and progression. Hence, we anticipate that the development of drugs reducing endogenous miR-155 levels might be key in the treatment of inflammation-related cancers. PMID:21383199

Tili, Esmerina; Michaille, Jean-Jacques; Wernicke, Dorothee; Alder, Hansjuerg; Costinean, Stefan; Volinia, Stefano; Croce, Carlo M.

2011-01-01

120

PfHPRT: a new biomarker candidate of acute Plasmodium falciparum infection.  

PubMed

Plasmodium falciparum is a protozoan parasite that causes human malaria. This parasitic infection accounts for approximately 655,000 deaths each year worldwide. Most deaths could be prevented by diagnosing and treating malaria promptly. To date, few parasite proteins have been developed into rapid diagnostic tools. We have combined a shotgun and a targeted proteomic strategy to characterize the plasma proteome of Gambian children with severe malaria (SM), mild malaria, and convalescent controls in search of new candidate biomarkers. Here we report four P. falciparum proteins with a high level of confidence in SM patients, namely, PF10_0121 (hypoxanthine phosphoribosyltransferase, pHPRT), PF11_0208 (phosphoglycerate mutase, pPGM), PF13_0141 (lactate dehydrogenase, pLDH), and PF14_0425 (fructose bisphosphate aldolase, pFBPA). We have optimized selected reaction monitoring (SRM) assays to quantify these proteins in individual patients. All P. falciparum proteins were higher in SM compared with mild cases or control subjects. SRM-based measurements correlated markedly with clinical anemia (low blood hemoglobin concentration), and pLDH and pFBPA were significantly correlated with higher P. falciparum parasitemia. These findings suggest that pHPRT is a promising biomarker to diagnose P. falciparum malaria infection. The diagnostic performance of this marker should be validated prospectively. PMID:23339668

Thézénas, Marie L; Huang, Honglei; Njie, Madi; Ramaprasad, Abhinay; Nwakanma, Davis C; Fischer, Roman; Digleria, Katalin; Walther, Michael; Conway, David J; Kessler, Benedikt M; Casals-Pascual, Climent

2013-03-01

121

Lentiviral vectors encoding zinc-finger nucleases specific for the model target locus HPRT1.  

PubMed

Zinc-finger nucleases (ZFNs) are artificial proteins designed to induce double-stranded DNA breaks (DSBs) at predefined chromosomal positions. These site-specific genomic lesions facilitate the study of translocations and cellular DNA repair processes and serve as powerful stimuli for the editing of complex genomes. The delivery of ZFNs into a wide range of cell types is of utmost importance for the broad evaluation and deployment of the technology. Lentiviral vectors (LVs) are versatile gene delivery vehicles that transduce alike transformed and primary cells regardless of their division rate. In this chapter, we describe the generation of conventional and integrase-defective LVs encoding ZFNs targeting the human hypoxanthine phosphoribosyltransferase 1 (HPRT1) locus. Furthermore, we introduce a general LV titration method based on a cost-effective quantitative PCR protocol and implement a rapid and simple restriction enzyme site polymorphism assay to detected DSB formation at the HPRT1 target sequence. Owing in part to the small molecule-based clone selection schemes conferred by HPRT1 allelic knockouts, this X-linked gene has become a "classical" target model locus in mammalian cells. The reagents and techniques detailed herein yield LV preparations that induce HPRT1-specific DSBs. As a result, they should constitute a valuable resource to increase the robustness and decrease the timelines of the various protocols based on HPRT1 gene disruption and targeting. PMID:24557904

Pelascini, Laetitia P L; Gonçalves, Manuel A F V

2014-01-01

122

Genetic Control of Metabolism of Mutagenic Purine Base Analogs 6-Hydroxylaminopurine and 2-Amino-6-Hydroxylaminopurine in Yeast Saccharomyces cerevisiae  

PubMed Central

We studied the effect of inactivation of genes, which control biosynthesis of inosine monophosphate (IMP)de novo and purine salvage and interconversion pathways, on sensitivity of yeast Saccharomyces cerevisiae to the mutagenic and toxic action of 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine(AHA). It was shown that the manifestation of HAP and AHA mutagenic properties depends on the action of enzyme adenine phosphoribosyltransferase encoded in yeast by APT1 gene. A blockade of any step of IMP biosynthesis, with the exception of the block mediated by inactivation of genes ADE16 and ADE17 leading to the accumulation of 5-aminoimidazole-4carboxamide ribonucleotide (AICAR), was shown to enhanceyeast cell sensitivity to the HAP mutagenic effect; however, it does not affect the sensitivity to AHA. A block of conversion of IMP into adenosine monophosphate (AMP) causes hypersensitivity of yeast cells to the mutagenic action of HAP and to the toxic effect of HAP, AHA, and hypoxanthine. It is possible that this enhancement of sensitivity to HAP and AHA is due to changes in the pool of purines. We conclude that genes ADE12, ADE13, AAH1, and HAM1 controlling processes of purine salvage and interconversion in yeast, make the greatest contribution to the protection against the toxic and mutagenic action of the examined analogs. Possible mechanisms of HAP detoxication in bacteria, yeast, and humans are discussed. PMID:19514135

Stepchenkova, E. I.; Kozmin, S. G.; Alenin, V. V.; Pavlov, Yu. I.

2014-01-01

123

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

PubMed Central

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

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

2012-01-01

124

Development and application of human cell lines engineered to metabolically activate structurally diverse environmental mutagens  

NASA Astrophysics Data System (ADS)

Cytochromes P450 are responsible for the mutagenic/carcinogenic activation of many environmental promutagens/procarcinogens. These enzymes are present at highest concentrations in liver in vivo but are markedly absent in tester organisms for most in vitro mutagenicity test systems. Two approaches have been used to supply needed metabolic activation, incorporation of an extracellular activating system, usually derived from a rodent liver and introduction of activating enzymes into the target cell. The latter approach appears to result in a more sensitive testing system because of the close proximity of the activating enzymes and the target DNA. Human cell lines have been developed which stably express human cytochromes P450 and other cDNAs which have been introduced individually or in combination. The resulting cell lines are exquisitely sensitive to exposure to promutagens and procarcinogens. Mutagenicity is measured at the hypoxanthine phosphoribosyl transferase (hprt) and thymidine kinase (tk) gene loci. The most versatile cell line, designated MCL-5, stably express five cDNAs encoding all of the human hepatic P450s known to be principally responsible for known human procarcinogen activation. The induction of mutation is observed in MCL-5 cells upon exposure to ng/ml levels of model compounds such as nitrosamines, aflatoxin B1 and benzo(a)pyrene. A lower volume mutagenicity assay has been developed for use with samples available in limited amounts. Human lymphoblast mutation assays have been used to screen for mutagenic activity sediment samples from a polluted watershed. Two sediment samples were found to have mutagenic activity to human lymphoblasts.

Crespi, C. I.; Langenbach, Robert; Gonzalez, Frank J.; Gelboin, Harry V.; Penman, B. W.

1993-03-01

125

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

PubMed Central

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

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

2014-01-01

126

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

PubMed

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

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

127

Method for the production of human T-T cell hybrids and production suppressor factor by human T-T cell hybrids  

SciTech Connect

This patent describes a method for production of human T-T cell hybrids which produce Suppressor Factor wherein cells of lymphoid origin are fused with comprises: (a) mixing cells from a first parent cell line comprising a non-mutagenized Jurkat lymoblastoid T cell line, wherein the Jurkat lymphoblastoid cells are not sensitive and cannot be killed by hypoxanthine-aminopterin-thymidine medium, with a second parent cell comprising mitogen or alloantigen activated peripheral blood leukocyte T cells or purified T-cells, (b) allowing the first and second parent cells to fuse in the presence of polyethylene glycol for about 10-20 minutes with gentle agitation to generate hybrids in the cell mixture, (c) incubating the cell mixture containing the hybrids and the first and second parent cells, after removal of the polyethylene glycol, for periods of between one to sixty days at 37{sup 0} in 5% CO/sub 2/, (d) selecting for the hybrids by separating the hybrids from the first parent Jurkat lymphoblastoid cells by coloning in agar medium wherein the hybrids form colonies, (e) recovering the hybrids that form colonies in agar medium and expanding them in culture, and (f) determining the presence of Suppressor Factor in the culture and recovering the T-T cell hybrids which produce suppressor factor.

Platsoucas, C.

1989-06-27

128

Human See, Human Do.  

ERIC Educational Resources Information Center

A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

Tomasello, Michael

1997-01-01

129

Human, Still Human!’  

Microsoft Academic Search

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

Jérôme Bindé

2005-01-01

130

Segregation of the NK-sensitive phenotype in human x mouse somatic cell hybrids reveals separate genetic control of recognition and postrecognition determinants.  

PubMed

In an attempt to investigate the nature of tumor cell-derived membrane surface determinants involved in natural killer cell (NK) recognition or postrecognition events, we have constructed human X mouse interspecies somatic cell hybrids. Highly NK-sensitive (NKs) human tumor cells were fused with NK resistant (NKr) mouse fibroblasts (LMTK-) in polyethylene glycol and selected in hypoxanthine/aminopterin/thymidine medium and ouabain. Hybrids generated from NKs erythroleukemia cells (K-562) or NKs retinoblastoma cells (Y-79) with LMTK- displayed an intermediate NK-sensitive phenotype. One Y-79 X LMTK- hybrid (YL-22) retained a high level of susceptibility to NK binding and cytolysis, as determined by 51Cr release and in cold-target inhibition assays. On the other hand, human NKr RAJI cells generated NK-resistant hybrids when fused with LMTK- fibroblasts. Four hybrids (KL-12, YL-2, YL-22, and YL-43) displaying consistent NK sensitivity were subsequently cloned by limiting dilution. Various hybrid clones derived from the KL-12 hybrid (K-562 X LMTK-) demonstrated a range of NK-sensitive phenotypes. However, the uncloned KL-12 and most cloned lines derived from this hybrid competed against 51Cr-labeled K-562 targets as well as unlabeled K-562 parental cells, regardless of their NK-sensitive phenotype. These findings raise the possibility that chromosomal segregation may be affecting a postbinding step in this hybrid system. The NK-sensitive hybrids exhibited a limited number of human chromosomes as assessed by quinacrine banding. Furthermore, human transferrin receptor (TfR) expression, as monitored by flow cytometry using the B3/25 monoclonal antibody, demonstrated no clear correlation with NK sensitivity or competitive ability in either KL or YL hybrid clones, thus arguing against the involvement of the TfR in human NK recognition. These results suggest that the NK-sensitive phenotype in human tumor cells may be regulated by genes encoded by a limited number of human chromosomes. PMID:2990738

Lauzon, R J; Roder, J C

1985-08-01

131

Fossil humans 1 Fossil humans  

E-print Network

Fossil 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 of the Neanderthal speci- men in 1856. Fossil human remains have come prin- cipally from Europe, Asia, China, Java

Delson, Eric

132

Long-term efficiency of mesenchymal stromal cell-mediated CD-MSC/5FC therapy in human melanoma xenograft model.  

PubMed

Mesenchymal stromal cells (MSC) can be exploited as cellular delivery vehicles for the enzymes converting non-toxic prodrugs to toxic substances. Because of their inherent chemoresistance, they exert potent bystander and antitumor effect. Here we show that the human adipose tissue-derived MSC expressing fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) in combination with 5-fluorocytosine (5FC) mediated a long-term tumor-free survival in the 83.3% of tumor-bearing animals. CD-MSC/5FC treatment induced cytotoxicity against model human melanoma cells EGFP-A375. Only 4% of the therapeutic CD-MSC cells eliminated >98.5% of the tumor cells in vitro. Long-term tumor-free survival was confirmed in 15 out of the 18 animals. However, repeatedly used CD-MSC/5FC therapeutic regimen generated more aggressive and metastatic variant of the melanoma cells EGFP-A375/Rel3. These cells derived from the refractory xenotransplants exhibited increased resistance to the CD-MSC/5FC treatment, altered cell adhesion, migration, tumorigenic and metastatic properties. However, long-term curative effect was achieved by the augmentation of the CD-MSC/5FC regimen along with the inhibition of c-Met/hepatocyte growth factor signaling axis in this aggressive melanoma derivative. In summary, the CD-MSC/5FC regimen can be regarded as a very effective antitumor approach to achieve long-term tumor-free survival as demonstrated on a mouse model of aggressive human melanoma xenografts. PMID:25056607

Kucerova, L; Skolekova, S; Demkova, L; Bohovic, R; Matuskova, M

2014-10-01

133

Charged-particle mutagenesis. 1. Cytotoxic and mutagenic effects of high-LET charged iron particles on human skin fibroblasts.  

PubMed

Cytotoxic and mutagenic effects of high-LET charged iron (56Fe) particles were measured quantitatively using primary cultures of human skin fibroblasts. Argon and lanthanum particles and gamma rays were used in comparative studies. The span of LETs selected was from 150 keV/microns (330 MeV/u) to 920 keV/microns (600 MeV/u). Mutations were scored at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus using 6-thio-guanine (6-TG) for selection. Exposure to these high-LET charged particles resulted in exponential survival curves. Mutation induction, however, was fitted by the linear model. The relative biological effectiveness (RBE) for cell killing ranged from 3.7 to 1.3, while that for mutation induction ranged from 5.7 to 0.5. Both the RBE for cell killing and the RBE for mutagenesis decreased with increasing LET over the range of 1.50 to 920 keV/microns. The inactivation cross section (sigma i) and the action cross section for mutation induction (sigma m) ranged from 32.9 to 92.0 microns2 and 1.45 to 5.56 X 10(-3) microns2; the maximum values were obtained by 56Fe with an LET of 200 keV/microns. The mutagenicity (sigma m/sigma i) ranged from 2.05 to 7.99 X 10(-5) with an inverse relationship to LET. PMID:1734447

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

1992-02-01

134

Human Development, Human Evolution.  

ERIC Educational Resources Information Center

One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a wholly new…

Smillie, David

135

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 ...

136

Human Ecology Human ecology Research  

E-print Network

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

Wang, Z. Jane

137

Transfer of nonselectable genes into mouse teratocarcinoma cells and transcription of the transferred human. beta. -globin gene  

SciTech Connect

Teratocarcinoma (TCC) stem cells can function as vehicles for the introduction of specific recombinant genes into mice. Because most genes do not code for a selectable marker, the authors investigated the transformation efficiency of vectors with a linked selectable gene. In one series, TCC cells first selected for thymidine kinase deficiency were treated with DNA from the plasmid vector PtkH..beta..1 containing the human genomic ..beta..-globin gene and the thymidine kinase gene of herpes simplex virus. A high transformation frequency was obtained after selection in hypoxanthine-aminopterin-thymidine medium. Hybridization tests revealed that the majority of transformants had intact copies of the human gene among three to six total copies per cell. These were associated with cellular DNA sequences as judged from the presence of additional new restriction fragments and from stability of the sequences in tumors produced by injecting the cells subcutaneously. Total polyadenylate-containing RNA from cell cultures of two out of four transformants examined showed hybridization to the human gene probe: one RNA species resembled mature human ..beta..-globin mRNA transcripts; the others were of larger size. In differentiating tumors, various tissues, including hematopoietic cells of TCC provenance could be found. In a second model set of experiments, wild-type TCC cells were used to test a dominant-selection scheme with pSV-gpt vectors. Numerous transformants were isolated, and their transfected DNA was apparently stably integrated. Thus, any gene of choice can be transferred into TCC stem cells even without mutagenesis of the cells, and selected cell clones can be characterized. Cells of interest may then be introduced into early embryos to produce new mouse strains with predetermined genetic changes.

Wagner, E.F.; Mintz, B.

1982-02-01

138

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)

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.

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

2002-01-01

139

ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1  

PubMed Central

Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia). A recent study in Icelanders identified a rare missense single nucleotide polymorphism (SNP) in the ALDH16A1 gene, ALDH16A1*2, to be associated with gout and serum uric acid levels. ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures. ALDH16 genes are present in fish, amphibians, protista, bacteria but absent from archaea, fungi and plants. In most mammalian species, two ALDH16A1 spliced variants (ALDH16A1, long form and ALDH16A1_v2, short form) have been identified and both are expressed in HepG-2, HK-2 and HK-293 human cell lines. The ALDH16 proteins contain two ALDH domains (as opposed to one in the other members of the superfamily), four transmembrane and one coiled-coil domains. The active site of ALDH16 proteins from bacterial, frog and lower animals contain the catalytically important cysteine residue (Cys-302); this residue is absent from the mammalian and fish orthologs. Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine-guanine phosphoribosyltransferase (HPRT1) protein, a key enzyme involved in uric acid metabolism and gout. Interestingly, such protein-protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A1*2. These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1*2 carriers. PMID:23348497

Vasiliou, Vasilis; Sandoval, Monica; Backos, Donald S.; Jackson, Brian C.; Chen, Ying; Reigan, Philip; Lanaspa, Miguel A.; Johnson, Richard J.; Koppaka, Vindhya; Thompson, David C.

2013-01-01

140

Proinflammatory and immunomodulatory cytokine mRNA time course profiles in hamsters infected with a virulent variant of Leptospira interrogans.  

PubMed

In order to quantify in vivo the mRNAs of cytokines which play important roles in leptospirosis, we have developed quantitative real-time PCR assays for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), transforming growth factor beta, and two housekeeping genes (encoding beta-actin and hypoxanthine phosphoribosyltransferase). We used a lethal hamster model reflecting severe leptospirosis in humans. The LightCycler system was used to quantify the gene expression levels with the SYBR green I detection format using external standard curves for each target. We compared the expression levels of cytokine mRNA in the peripheral blood mononuclear cells of both control (uninfected) hamsters and Leptospira interrogans-inoculated hamsters from 1 to 24 h and then 1 to 4 days postinfection. In this kinetic study, there was pronounced expression of Th1 cytokine mRNA (TNF-alpha, IFN-gamma, and IL-12), with transcripts being detected as early as 1 h postinfection. Expression of anti-inflammatory cytokines, such as IL-4 and IL-10, was prominent in delayed samples from 1 to 4 days postinfection in response to infection with Leptospira interrogans. Our data are the first to establish that pathogenic leptospires can stimulate in vivo the production of type 1 cytokines involved in cellular immunity by using this informative animal model. Measuring and assessing cytokine profiles may provide a useful method for accurate study of the mechanisms of anti-Leptospira immunity, indications of prognosis factors, and prospective evaluation of leptospirosis vaccine efficacy in humans. PMID:16790792

Vernel-Pauillac, Frédérique; Merien, Fabrice

2006-07-01

141

A Phosphoenzyme Mimic, Overlapping Catalytic Sites and Reaction Coordinate Motion for Human NAMPT  

SciTech Connect

Nicotinamide phosphoribosyltransferase (NAMPT) is highly evolved to capture nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD+) pool during ADP-ribosylation and transferase reactions. ATP-phosphorylation of an active-site histidine causes catalytic activation, increasing NAM affinity by 160,000. Crystal structures of NAMPT with catalytic site ligands identify the phosphorylation site, establish its role in catalysis, demonstrate unique overlapping ATP and phosphoribosyltransferase sites, and establish reaction coordinate motion. NAMPT structures with beryllium fluoride indicate a covalent H247-BeF3- as the phosphohistidine mimic. Activation of NAMPT by H247-phosphorylation causes stabilization of the enzyme-phosphoribosylpyrophosphate complex, permitting efficient capture of NAM. Reactant and product structures establish reaction coordinate motion for NAMPT to be migration of the ribosyl anomeric carbon from the pyrophosphate leaving group to the nicotinamide-N1 while the 5-phosphoryl group, the pyrophosphate moiety, and the nicotinamide ring remain fixed in the catalytic site.

Burgos, E.; Ho, M; Almo, S; Schramm, V

2009-01-01

142

Mutagenicity and cytotoxicity of five antitumor ellipticines in mammalian cells and their structure-activity relationships in Salmonella  

SciTech Connect

The mutagenicity and cytotoxicity of five antitumor compounds (ellipticines) were investigated in the Chinese hamster ovary cell hypoxanthine-guanine phosphoribosyltransferase assay and in six strains of Salmonella. All five compounds (ellipticine, 9-methoxyellipticine, 9-hydroxyellipticine, 9-aminoellipticine, and 2-methyl-9-hydroxyellipticinium) were cytotoxic and mutagenic in the Chinese hamster ovary cell hypoxanthine-guanine phosphoribosyltransferase assay in the presence or absence of Aroclor 1254-induced rat liver S9, and all except the last compound were mutagenic in Salmonella. Based on the reversion pattern obtained in various frame-shift and DNA repair-proficient (uvrB/sup +/) or -deficient (uvrB) strains of Salmonella in the presence or absence of S9, the first three compounds appear to cause frameshift mutations by both intercalation and covalent bonding with DNA; thus, these are classified as reactive intercalators. However, 9-aminoellipticine intercalates only weakly and may instead exert its mutagenic activity primarily (or exclusively) by forming a covalent adduct with DNA. Compared to the published antitumor data obtained in mice, the results in Salmonella and Chinese hamster ovary cells suggest that the ability of ellipticine, 9-methoxyellipticine, and 9-hydroxyellipticine to intercalate with DNA, induce frame-shift mutations, and cause cell killing is associated with and may be the basis for their antitumor activity. The observation that the ellipticines are mutagenic in mammalian cells suggests that these antitumor agents may be carcinogenic.

DeMarini, D.M.; Cros, S.; Paoletti, C.; Lecointe, P.; Hsie, A.W.

1983-08-01

143

Normal uricemia in lesch-nyhan syndrome and the association with pulmonary embolism in a young child-a case report and literature review.  

PubMed

Deficiency of hypoxanthine phosphoribosyltransferase activity is a rare inborn error of purine metabolism with subsequent uric acid overproduction and neurologic presentations. The diagnosis of Lesch-Nyhan syndrome (LNS) is frequently delayed until self-mutilation becomes evident. We report the case of a boy aged 1 year and 10 months who was diagnosed with profound global developmental delay, persistent chorea, and compulsive self-mutilation since the age of 1 year. Serial serum uric acid levels showed normal uric acid level, and the spot urine uric acid/creatinine ratio was >2. The hypoxanthine phosphoribosyltransferase cDNA showed the deletion of exon 6, and the boy was subsequently diagnosed to have LNS. He also had respiratory distress due to pulmonary embolism documented by chest computed tomography scan. This report highlights the need to determine the uric acid/creatinine ratio caused by increased renal clearance in LNS in young children. The presence of pulmonary embolism is unusual and may be the consequence of prolonged immobilization. PMID:23597535

Tsai, Jeng-Dau; Chen, Shan-Ming; Lin, Chien-Heng; Ku, Min-Sho; Tsao, Teng-Fu; Sheu, Ji-Nan

2014-08-01

144

Human Evolution  

NSDL National Science Digital Library

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.

Macevoy, Bruce

1969-12-31

145

Glyoxylate lowers metabolic ATP in human platelets without altering adenylate energy charge or aggregation.  

PubMed

Human blood platelets adhere to exposed collagen at the site of vascular injury, initiating a signaling cascade leading to fibrinogen activation, secretion of granules and aggregation, thus producing a stable thrombus. All these steps require metabolic ATP. In this study we have labeled the metabolic pool of ATP with nucleotides, treated platelets with various inhibitors and have monitored their ability to be activated. Incubating platelets with glyoxylate dramatically reduced the ATP level without a change in the adenylate energy charge (AEC). This reduction of ATP did not affect ADP-induced primary or secondary aggregation, whereas glyoxal, methyl glyoxal, or the combination of antimycin plus deoxyglucose reduced both ATP and AEC and inhibited aggregation. The reduction of ATP by glyoxylate was almost quantitatively matched by an increase in hypoxanthine without elevation of ADP. AMP, IMP or inosine, acetoacetate, aspartate, or glutamate had no effect on glyoxylate-induced breakdown of ATP, while pyruvate stopped the ATP reduction fast and efficiently. Glyoxylate also lowered the citrate content. The glyoxylate-induced breakdown of ATP coincided with an increase in fructose-1,6-bisphosphate, indicating that the phosphofructokinase reaction was the main ATP-consuming step. Glyoxylate was a substrate for lactate dehydrogenase although with a Km almost 100 times higher than pyruvate. We suggest that glyoxylate primarily competes with pyruvate in the pyruvate dehydrogenase reaction, thus lowering the citrate concentration, which in turn activates phosphofructokinase. Clearly, lowering of ATP in the cytosol by more than 50% does not affect platelet aggregation provided that the AEC is not reduced. PMID:23488475

Dangelmaier, Carol A; Holmsen, Holm

2014-01-01

146

Effects of hypothermic ischemia on purine catabolism in canine, primate, and human myocardium.  

PubMed

After hypothermic cardiac arrest, creatine phosphate (CrP) and adenine nucleotide catabolism was compared in myocardium from dogs (n = 7), baboons (n = 5), and man (n = 7; patients undergoing cardiac transplantation) during cold (0.5 degree C) storage for up to 24 hours. Although hypothermia delayed the catabolism in dog myocardium it still remained very extensive. CrP dropped to virtually nil and ATP fell to below 15% of the total purines within 6 hours. The majority of the adenine nucleotides was broken down to adenosine (ADO; 32% of total purines) and inosine (INO; 21%). Apart from the delay (7 to 9-fold), hypothermia also reversed the ratio between ADO and INO when compared to normothermia, suggesting a profound effect of temperature on the nucleoside transporter. In human myocardium even after 12 hours of hypothermia ATP still contributed more than 60% to the total purines. Concomitantly, nucleoside formation proceeded slowly with almost no intermediate ADO. Under similar conditions, the catabolism of ATP in baboon myocardium occurred at a higher rate than in man but still far below canine metabolism. Irrespective of the relatively higher fall in ATP, ADP and AMP accumulated more in baboon myocardium indicating a limited dephosphorylation of the nucleotides. Only in the baboon myocardium did inosine monophosphate increase above the detection limits. In none of the species did purine catabolism proceed beyond hypoxanthine and even this could hardly be detected in the primates. It is concluded that considerable species differences do exist in the rate as well as in the pattern of nucleotide catabolism even during storage of the myocardium at low temperature. PMID:1948966

Möllhoff, T; Sukehiro, S; Hendrickx, M; Van Belle, H; Flameng, W

1991-08-01

147

Misrejoining of DNA double-strand breaks in primary and transformed human and rodent cells: a comparison between the HPRT region and other genomic locations.  

PubMed

Many studies of radiation response and mutagenesis have been carried out with transformed human or rodent cell lines. To study whether the transfer of results between different cellular systems is justified with regard to the repair of radiation-induced DNA double-strand breaks (DSBs), two assays that measure the joining of correct DSB ends and total rejoining in specific regions of the genome were applied to primary and cancer-derived human cells and a Chinese hamster cell line. The experimental procedure involves Southern hybridization of pulsed-field gel electrophoresis blots and quantitative analysis of specific restriction fragments detected by a single-copy probe. The yield of X-ray-induced DSBs was comparable in all cell lines analyzed, amounting to about 1 x 10(-2) breaks/Mbp/Gy. For joining correct DSB ends following an 80 Gy X-ray exposure all cell lines showed similar kinetics and the same final level of correctly rejoined breaks of about 50%. Analysis of all rejoining events revealed a considerable fraction of unrejoined DSBs (15-20%) after 24 h repair incubation in the tumor cell line, 5-10% unrejoined breaks in CHO cells and complete DSB rejoining in primary human fibroblasts. To study intragenomic heterogeneity of DSB repair, we analyzed the joining of correct and incorrect break ends in regions of different gene density and activity in human cells. A comparison of the region Xq26 spanning the hypoxanthine guanine phosphoribosyl transferase locus with the region 21q21 revealed identical characteristics for the induction and repair of DSBs, suggesting that there are no large variations between Giemsa-light and Giemsa-dark chromosomal bands. PMID:10343652

Rothkamm, K; Löbrich, M

1999-04-01

148

Human Anatomy  

NSDL National Science Digital Library

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 ...

Schultz, Ms.

2007-11-09

149

Clonal Expansions of 6-Thioguanine Resistant T Lymphocytes in the Blood and Tumor of Melanoma Patients1  

PubMed Central

The identification of specific lymphocyte populations that mediate tumor immune responses is required for elucidating the mechanisms underlying these responses and facilitating therapeutic interventions in humans with cancer. To this end, mutant hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficient (HPRT-) T-cells were employed as probes to detect T-cell clonal amplifications and trafficking in vivo in patients with advanced melanoma. Mutant T-cells from peripheral blood were obtained as clonal isolates or in mass cultures in the presence of 6-thioguanine (TG) selection, and from tumor-bearing lymph nodes or metastatic melanoma tissues by TG-selected mass cultures. Non-mutant (wild-type) cells were obtained from all sites by analogous means, but without TG selection. cDNA sequences of the T-cell receptor (TCR) beta chains (TCR-?), determined directly (clonal isolates) or following insertion into plasmids (mass cultures), were used as unambiguous biomarkers of in vivo clonality of mature T-cell clones. Clonal amplifications, identified as repetitive TCR-? V-region, complementarity determining region 3 (CDR3), and J-region gene sequences, were demonstrated at all sites studied, i.e., peripheral blood, lymph nodes, and metastatic tumors. Amplifications were significantly enriched among the mutant compared with the wild-type T-cell fractions. Importantly, T-cell trafficking was manifest by identical TCR-? cDNA sequences, including the hyper-variable CDR3 motifs, being found in both blood and tissues in individual patients. The findings described herein indicate that the mutant T-cell fractions from melanoma patients are enriched for proliferating T-cells that infiltrate the tumor, making them candidates for investigations of potentially protective immunological responses. PMID:18712786

Albertini, Mark R.; Macklin, Michael D.; Zuleger, Cindy L.; Newton, Michael A.; Judice, Stephen A.; Albertini, Richard J.

2011-01-01

150

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

SciTech Connect

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.

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

1995-06-01

151

Genetic manipulation in ?ku80 strains for functional genomic analysis of Toxoplasma gondii.  

PubMed

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 protein(1,2). 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 scale(1-4). 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

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

2013-01-01

152

Human cloning and human dignity  

Microsoft Academic Search

Judging from the official documents dealing with the moral and legal aspects of human reproductive cloning there seems to be a nearly worldwide consensus that reproductive cloning is incompatible with human dignity. The certainty of this judgement is, however, not matched by corresponding arguments. Is the incompatibility of reproductive with human dignity an ultimate moral intuition closed to further argument?

Dieter Birnbacher

2005-01-01

153

Different mechanisms of radiation-induced loss of heterozygosity in two human lymphoid cell lines from a single donor  

NASA Technical Reports Server (NTRS)

Allelic loss is an important mutational mechanism in human carcinogenesis. Loss of heterozygosity (LOH) at an autosomal locus is one outcome of the repair of DNA double-strand breaks (DSBs) and can occur by deletion or by mitotic recombination. We report that mitotic recombination between homologous chromosomes occurred in human lymphoid cells exposed to densely ionizing radiation. We used cells derived from the same donor that express either normal TP53 (TK6 cells) or homozygous mutant TP53 (WTK1 cells) to assess the influence of TP53 on radiation-induced mutagenesis. Expression of mutant TP53 (Met 237 Ile) was associated with a small increase in mutation frequencies at the hemizygous HPRT (hypoxanthine phosphoribosyl transferase) locus, but the mutation spectra were unaffected at this locus. In contrast, WTK1 cells (mutant TP53) were 30-fold more susceptible than TK6 cells (wild-type TP53) to radiation-induced mutagenesis at the TK1 (thymidine kinase) locus. Gene dosage analysis combined with microsatellite marker analysis showed that the increase in TK1 mutagenesis in WTK1 cells could be attributed, in part, to mitotic recombination. The microsatellite marker analysis over a 64-cM region on chromosome 17q indicated that the recombinational events could initiate at different positions between the TK1 locus and the centromere. Virtually all of the recombinational LOH events extended beyond the TK1 locus to the most telomeric marker. In general, longer LOH tracts were observed in mutants from WTK1 cells than in mutants from TK6 cells. Taken together, the results demonstrate that the incidence of radi-ation-induced mutations is dependent on the genetic background of the cell at risk, on the locus examined, and on the mechanisms for mutation available at the locus of interest.

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

2001-01-01

154

Different mechanisms of radiation-induced loss of heterozygosity in two human lymphoid cell lines from a single donor.  

PubMed

Allelic loss is an important mutational mechanism in human carcinogenesis. Loss of heterozygosity (LOH) at an autosomal locus is one outcome of the repair of DNA double-strand breaks (DSBs) and can occur by deletion or by mitotic recombination. We report that mitotic recombination between homologous chromosomes occurred in human lymphoid cells exposed to densely ionizing radiation. We used cells derived from the same donor that express either normal TP53 (TK6 cells) or homozygous mutant TP53 (WTK1 cells) to assess the influence of TP53 on radiation-induced mutagenesis. Expression of mutant TP53 (Met 237 Ile) was associated with a small increase in mutation frequencies at the hemizygous HPRT (hypoxanthine phosphoribosyl transferase) locus, but the mutation spectra were unaffected at this locus. In contrast, WTK1 cells (mutant TP53) were 30-fold more susceptible than TK6 cells (wild-type TP53) to radiation-induced mutagenesis at the TK1 (thymidine kinase) locus. Gene dosage analysis combined with microsatellite marker analysis showed that the increase in TK1 mutagenesis in WTK1 cells could be attributed, in part, to mitotic recombination. The microsatellite marker analysis over a 64-cM region on chromosome 17q indicated that the recombinational events could initiate at different positions between the TK1 locus and the centromere. Virtually all of the recombinational LOH events extended beyond the TK1 locus to the most telomeric marker. In general, longer LOH tracts were observed in mutants from WTK1 cells than in mutants from TK6 cells. Taken together, the results demonstrate that the incidence of radi-ation-induced mutations is dependent on the genetic background of the cell at risk, on the locus examined, and on the mechanisms for mutation available at the locus of interest. PMID:11221843

Wiese, C; Gauny, S S; Liu, W C; Cherbonnel-Lasserre, C L; Kronenberg, A

2001-02-01

155

Structural Insights into the Function of the Nicotinate Mononucleotide:phenol/pcresol Phosphoribosyltransferase (ArsAB)  

E-print Network

cobamides,7 and unique among cobamides are those with phenol or p-cresol as the lower ligand (Figure 1C neither phenol nor p-cresol contains an atom that can establish a coordination bond with the Co ion

Rayment, Ivan

156

Bis(benzyl)polyamine analogs inhibit the growth of chloroquine-resistant human malaria parasites (Plasmodium falciparum) in vitro and in combination with alpha-difluoromethylornithine cure murine malaria.  

PubMed Central

A number of bis(benzyl)polyamine analogs were found to be potent inhibitors of both chloroquine-resistant and chloroquine-sensitive strains of the human malaria parasite Plasmodium falciparum in vitro (IC50 values = 0.2-14 microM). Administration of one of the compounds, MDL 27695, which is N,N'-bis(3-[(phenylmethyl)amino]propyl)-1,7-diaminoheptane (C6H5CH2NH(CH2)3NH(CH2)7NH(CH2)3NHCH2C6H5), at 10-15 mg/kg i.p. three times per day for 3 days in combination with 2% alpha-difluoromethylornithine (DFMO; eflornithine) in drinking water effected cures of 47/54 mice infected with Plasmodium berghei. Cured mice were found to be immune upon rechallenge with the same P. berghei strain 4 months after the initial infection and drug-induced cure. MDL 27695 rapidly inhibited the incorporation of [3H]hypoxanthine into P. falciparum RNA and DNA, whereas the incorporation of [3H]isoleucine was not affected until much later. We conclude, therefore, that the major cytotoxic event may be direct binding of MDL 27695 to DNA with subsequent disruption of macromolecular biosynthesis and cell death. These compounds offer a lead in the search for new agents for chemotherapy of malaria. PMID:2463635

Bitonti, A J; Dumont, J A; Bush, T L; Edwards, M L; Stemerick, D M; McCann, P P; Sjoerdsma, A

1989-01-01

157

Human Evolution  

NSDL National Science Digital Library

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.

Lee, Amy.

2002-01-01

158

Human Aggression.  

National Technical Information Service (NTIS)

The paper presents an approach to human aggression concerned with environmental stimuli. Details of recent studies and analysis of aversive stimuli and reinforcing stimuli are presented. The paper concludes by suggesting some possible generalizations from...

R. E. Ulrich, J. E. Favell

1968-01-01

159

Human monkeypox.  

PubMed

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

McCollum, Andrea M; Damon, Inger K

2014-01-01

160

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.

161

Humanizing Calculus  

ERIC Educational Resources Information Center

In this article, the author explores the history and the mathematics used by Newton and Leibniz in their invention of calculus. The exploration of this topic is intended to show students that mathematics is a human invention. Suggestions are made to help teachers incorporate the mathematics and the history into their own lessons. (Contains 3…

Cirillo, Michelle

2007-01-01

162

Human Trafficking  

ERIC Educational Resources Information Center

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…

Wilson, David McKay

2011-01-01

163

Human Levitation  

Microsoft Academic Search

Human levitation occurs when the physical body rises into the air seemingly in defiance of the force of gravity. Traditionally most levitation reports have originated from seven groups: (i) mysticism, (ii) shamanism, (iii) people supposedly possessed by demonic spiritual entities, (iv) those subjected to poltergeist activity, (v) Spiritualism, (vi) people who believe they have been abducted by aliens, and (vii)

SIMON HARVEY-WILSON

2006-01-01

164

Nothing Human  

ERIC Educational Resources Information Center

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…

Wharram, C. C.

2014-01-01

165

Human torso  

NSDL National Science Digital Library

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.

William Cheselden (None;)

2000-04-02

166

Human Effect  

NSDL National Science Digital Library

In this lesson, students will investigate changes in air quality due to human interaction particularly burning of fossil fuels, and crop burning which increase levels of carbon monoxide. Students will evaluate changes in air quality over a 6 month time frame using Air Quality-Carbon Monoxide Data and draw conclusions based on observing color plot comparison graphs.

167

Human monkeypox.  

PubMed

Human monkeypox, occurring in the tropical rainforest of west and central Africa, is regarded as the most important orthopoxvirus infection for epidemiological surveillance during the post-smallpox era. This disease, first recognized in Zaïre in 1970 resembles smallpox clinically but differs epidemiologically. Clinical features, their evolution and sequelae of monkeypox could be compared with discrete ordinary or modified type of smallpox. A case-fatality rate of 14% has been observed but some cases can be exceedingly mild or atypical and may easily remain undetected and unreported. Pronounced lymphadenopathy has been the only clinical feature found commonly in monkeypox but not in smallpox. Fifty-seven cases of human monkeypox have occurred since 1970, in the tropical rainforests in six west and central African countries, the majority of them (45) being reported from Zaïre. The disease appears to be more frequent in dry season. Children below ten years of age comprise 84% of the cases. Smallpox vaccination protects against monkeypox. Clusters of cases have been observed in certain areas within countries and within affected households. Human-to-human spread has possibly occurred seven times. No cases of possible tertiary spread were observed. The secondary attack rate among susceptible close household contacts was 10%, among all susceptible contacts 5%. This is much lower than that occurring with smallpox, which is between 25-40%. The limited avidity of monkeypox virus for human beings indicates that monkeypox is probably a zoonosis, although the animal reservoir(s) have not yet been identified. The low transmissibility, resulting in low frequency of disease in man indicates that monkeypox is not a public health problem. Human monkeypox has been a relatively newly recognized disease. Studies are in progress to identify the natural cycle of monkeypox virus and to define better its clinical and epidemiological characteristics. Special surveillance is maintained in endemic areas with the aim to provide assurance that in spite of waning immunity of the human population following cessation of the smallpox vaccination, the disease does not constitute a potential danger to man. PMID:6304185

Jezek, Z; Gromyko, A I; Szczeniowski, M V

1983-01-01

168

Human Ectoparasites  

NSDL National Science Digital Library

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).

Sohmer, Rachel.

169

Human papillomavirus.  

PubMed

In the past year, new data have been published on the molecular biology of human papillomavirus infections and their relationship to cervical neoplasia. As molecular techniques have become more sophisticated and as the molecular knowledge of human papilloma-virus infections has been pursued in greater depth, it is increasingly apparent that this human tumor DNA virus is similar to a number of other oncogenic DNA viruses that have been described and well studied. These viruses appear to act through a common pathway of producing oncogenic proteins that interfere with key signalling elements that normally control the process of cell division. With a better mechanistic knowledge, it should be possible to design new therapeutic approaches to treating human papillomavirus-associated disease that are directed toward specific cellular events such as turning off the production of E6 and E7 proteins or restoring the activity of pRB or p53. Increased attention has also been turned to immunologic aspects of HPV infections, and a number of groups are eagerly pursuing the possibility of using simple office-based procedures to detect specific proteins encoded for by the human papillomavirus open reading frames in an attempt to determine who has been infected, is actively infected, and has proteins being produced that are indicative of neoplasia. From the clinical point of view, the use of outpatient excisional techniques such as the loop electrosurgical excision procedure is rapidly supplanting ablative techniques because of their superior ability to identify early invasive carcinomas and adenocarcinomas in situ that have not been detected by colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1327250

Richart, R M; Wright, T C

1992-10-01

170

Human Capital, (Human) Capabilities and Higher Education  

ERIC Educational Resources Information Center

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…

Le Grange, L.

2011-01-01

171

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.

172

Human Locomotion  

PubMed Central

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

Inman, Verne T.

1966-01-01

173

Human Protothecosis  

PubMed Central

Human protothecosis is a rare infection caused by members of the genus Prototheca. Prototheca species are generally considered to be achlorophyllic algae and are ubiquitous in nature. The occurrence of protothecosis can be local or disseminated and acute or chronic, with the latter being more common. Diseases have been classified as (i) cutaneous lesions, (ii) olecranon bursitis, or (iii) disseminated or systemic manifestations. Infections can occur in both immunocompetent and immunosuppressed patients, although more severe and disseminated infections tend to occur in immunocompromised individuals. Prototheca wickerhamii and Prototheca zopfii have been associated with human disease. Usually, treatment involves medical and surgical approaches; treatment failure is not uncommon. Antifungals such as ketoconazole, itraconazole, fluconazole, and amphotericin B are the most commonly used drugs to date. Among them, amphotericin B displays the best activity against Prototheca spp. Diagnosis is largely made upon detection of characteristic structures observed on histopathologic examination of tissue. PMID:17428884

Lass-Florl, Cornelia; Mayr, Astrid

2007-01-01

174

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.

175

Human Chromosomes  

NSDL National Science Digital Library

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.

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

2005-03-12

176

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

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

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

2013-01-01

177

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

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

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

2013-01-01

178

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

PubMed

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

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

2014-11-01

179

Human Speedy  

PubMed Central

The decision for a cell to self-replicate requires passage from G1 to S phase of the cell cycle and initiation of another round of DNA replication. This commitment is a critical one that is tightly regulated by many parallel pathways. Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of cell progression. Here we report the identification and characterization of a novel cell cycle gene, designated Speedy (Spy1). Spy1 is 40% homologous to the Xenopus cell cycle gene, X-Spy1. Similar to its Xenopus counterpart, human Speedy is able to induce oocyte maturation, suggesting similar biological characteristics. Spy1 mRNA is expressed in several human tissues and immortalized cell lines and is only expressed during the G1/S phase of the cell cycle. Overexpression of Spy1 protein demonstrates that Spy1 is nuclear and results in enhanced cell proliferation. In addition, flow cytometry profiles of these cells demonstrate a reduction in G1 population. Changes in cell cycle regulation can be attributed to the ability of Spy1 to bind to and prematurely activate cdk2 independent of cyclin binding. We demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2 activation. Furthermore, abrogation of Spy1 expression, through the use of siRNA, demonstrates that Spy1 is an essential component of cell proliferation pathways. Hence, human Speedy is a novel cell cycle protein capable of promoting cell proliferation through the premature activation of cdk2 at the G1/S phase transition. PMID:11980914

Porter, Lisa A.; Dellinger, Ryan W.; Tynan, John A.; Barnes, Elizabeth A.; Kong, Monica; Lenormand, Jean-Luc; Donoghue, Daniel J.

2002-01-01

180

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 ...

181

Human schistosomiasis.  

PubMed

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

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

2014-06-28

182

[Human metapneumovirus].  

PubMed

Human metapneumovirus (hMPV), first isolated in the Netherlands in 2001, is a member of the genus Metapneumovirus of the sub-family Pneumovirinae of the family Paramyxoviridae. The genomic organization of hMPV is 3'-N-P-M-F-M2-SH-G-L-5'. hMPV resembles the sole member of this genus, avian pneumovirus. hMPV is the most closely related human pathogen to respiratory syncytial virus. Phylogenetic analysis of the nucleotide sequences indicated that there were two genetic groups. Furthermore, each group could be subdivided into two subgroups. hMPV encodes three surface proteins, F, G and SH proteins. The majority of antibodies to hMPV in serum were antibody against F protein, which mediates cross-group neutralization and protection. The incidences of hMPV-associated respiratory infection estimate 5 to 10% in children and 2 to 4% in adults. hMPV generally causes upper respiratory tract infection and flu-like illness, the virus can be associated with lower tract infections, such as wheezy bronchitis, bronchitis, bronchiolitis and pneumonia, in very young children, elderly persons, and immunocompromised patients. hMPV has a seasonal peak during the spring in Japan. Reinfection with hMPV frequently occurs in children, implying that the host immune response induced by natural infection provides incomplete protection. The RT-PCR test is the most sensitive test for detection of hMPV. PMID:17446666

Kikuta, Hideaki

2006-12-01

183

Carbocyclic Analogues of Inosine-5'-Monophosphate: Synthesis and Biological Activity  

PubMed Central

9-(4’-Phosphonomethoxy-2’-cyclopenten-1’-yl)hypoxanthine and 9-(4’-phosphonomethoxy-2’,3’-dihydroxycyclopenten-1’-yl)hypoxanthine were synthesized as isosteric carbocyclic analogues of inosine-5’-monophosphate. The synthesized compounds were shown to be capable of inhibiting the activity of human type II inosine-5?-monophosphate dehydrogenase (IMPDH II) (IC50 = 500 µM) and to have no significant effects on the growth ofMycobacterium tuberculosis. PMID:23346382

Matyugina, E.S.; Andreevskaya, S.N.; Smirnova, T.G.; Khandazhinskaya, A.L.

2012-01-01

184

Human Clones and International Human Rights  

Microsoft Academic Search

The United Nations Declaration on Human Cloning calls upon member states to prohibit all forms of human cloning. However, the Declaration is nonbinding and will not put a stop to cloning around the world. Scientists will continue to clone embryos in their quest to develop stem cell therapies, ultimately, their work will facilitate the birth of human clones.;Once born, human

Kerry MacIntosh

2006-01-01

185

Human Subjects Section 6. Protection of Human  

E-print Network

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

Heller, Barbara

186

HUMAN SERVICES ANNEX O HUMAN SERVICES  

E-print Network

ANNEX O HUMAN SERVICES #12;ANNEX O ­ HUMAN SERVICES 07/25/2012 v.1.0 Page O-1 PROMULGATION STATEMENT Annex O: Human Services, and contents within, is a guide to how the University provides human Office of Safety and Security Texas A&M University #12;ANNEX O ­ HUMAN SERVICES 07/25/2012 v.1.0 Page O-2

187

Damage to Aspergillus fumigatus and Rhizopus oryzae Hyphae by Oxidative and Nonoxidative Microbicidal Products of Human Neutrophils In Vitro  

PubMed Central

Our previous studies established that human neutrophils could damage and probably kill hyphae of Aspergillus fumigatus and Rhizopus oryzae in vitro, primarily by oxygen-dependent mechanisms active at the cell surface. These studies were extended, again quantitating hyphal damage by reduction in uptake of 14C-labeled uracil or glutamine. Neither A. fumigatus nor R. oryzae hyphae were damaged by neutrophils from patients with chronic granulomatous disease, confirming the importance of oxidative mechanisms in damage to hyphae. In contrast, neutrophils from one patient with hereditary myeloperoxidase deficiency damaged R. oryzae but not A. fumigatus hyphae. Cell-free, in vitro systems were then used to help determine the relative importance of several potentially fungicidal products of neutrophils. Both A. fumigatus and R. oryzae hyphae were damaged by the myeloperoxidase-hydrogen peroxide-halide system either with reagent hydrogen peroxide or enzymatic systems for generating hydrogen peroxide (glucose oxidase with glucose, or xanthine oxidase with either hypoxanthine or acetaldehyde). Iodide with or without chloride supported the reaction, but damage was less with chloride alone as the halide cofactor. Hydrogen peroxide alone damaged hyphae only in concentrations ?1 mM, but 0.01 mM hypochlorous acid, a potential product of the myeloperoxidase system, significantly damaged R. oryzae hyphae (a 1 mM concentration was required for significant damage to A. fumigatus hyphae). Damage to hyphae by the myeloperoxidase system was inhibited by azide, cyanide, catalase, histidine, and tryptophan, but not by superoxide dismutase, dimethyl sulfoxide, or mannitol. Photoactivation of the dye rose bengal resulted in hyphal damage which was inhibited by histidine, tryptophan, and 1,4-diazobicyclo(2,2,2)octane. Lysates of neutrophils or separated neutrophil granules did not affect A. fumigatus hyphae, but did damage R. oryzae hyphae. Similarly, three preparations of cationic proteins purified from human neutrophil granules were more active in damaging R. oryzae than A. fumigatus hyphae. This damage, as with the separated granules and whole cell lysates, was inhibited by the polyanion heparin. Damage to R. oryzae hyphae by neutrophil cationic proteins was enhanced by activity of the complete myeloperoxidase system or by hydrogen peroxide alone in subinhibitory concentrations. These data support the importance of oxidative products in general and the myeloperoxidase system in particular in damage to hyphae by neutrophils. Cationic proteins may also contribute significantly to neutrophil-mediated damage to R. oryzae hyphae. PMID:6292103

Diamond, Richard D.; Clark, Robert A.

1982-01-01

188

Human development?  

PubMed

This pamphlet gives a summary of the UN "Human Development Report, 1992" for developed countries in general and developing countries in general. Each country's ranking in the Human Development Index, 1992, is given. Scores range from 0.05 to 1.0, and are based on longevity, knowledge, and income. The Philippines' score of 0.6 ranks them 80th out of 160 countries. Global distribution of income is reported as 20% of the richest receiving 82.7% of the total world income while the poorest 20% receive only 1.4%. The second highest 20% receive 11.7% of the total world income; the middle 20% receive 2.3%; the second to the poorest 20% receive 1.9%. Developing countries have demonstrated progress in increased life expectancy, which in 26 developing countries is over 70 years. The average is 63 years. 66% have access to health services. Access to safe drinking water has improved considerably. Public expenditures on health as a proportion of gross national product have increased substantially. Adult literacy improved by over 33% since 1970. Almost 75% of children are enrolled in schools. Earnings, social security benefits, child mortality, immunization, and gaps between men and women in primary education have all improved in developing countries. The findings on deprivation still show 14 million child deaths annually, 1.5 billion people without access to health services, 1.3 billion without access to safe drinking water, and 2.3 billion people without access to sanitation. Almost 1 billion adults (600 million women) are illiterate. 1.2 billion people still live in absolute poverty where survival is threatened. In Sub-Saharan Africa, 1 in 40 adults and almost 1 million children are HIV infected. In developed countries 1 in 3 adults smokes, 5 in every 1000 are seriously injured in auto accidents, 33% of adults have not completed secondary education, the ratio of teachers to soldiers is 100:97, 30 million are unemployed in OECD countries, the gap between rich and poor is very wide, 1 in every 500 is in jail, homicide and divorce rates are high, and environmental pollution is a major concern. PMID:12179224

1993-02-01

189

Update on the phenotypic spectrum of Lesch-Nyhan disease and its attenuated variants.  

PubMed

Congenital deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a spectrum of clinical phenotypes. All of these phenotypes are associated with marked overproduction of uric acid and related problems such as hyperuricemia, urate nephrolithiasis, tophi, and gout. The mildest phenotypes include only problems related to overproduction of uric acid. The most severe phenotype is known as Lesch-Nyhan disease, in which the phenotype also includes severe motor handicap, intellectual disability, and self-injurious behavior. In between these two extremes is a continuous spectrum of phenotypes with varying degrees of motor and cognitive handicap but no self-injurious behavior. The pathogenesis of overproduction of uric acid in HPRT deficiency is well-understood, and treatments are available to control it. The pathogenesis of the neurobehavioral problems is less well-understood, and effective treatments for them are lacking. PMID:22198833

Torres, Rosa J; Puig, Juan G; Jinnah, H A

2012-04-01

190

Embryonic stem cells expressing expanded CAG repeats undergo aberrant neuronal differentiation and have persistent Oct-4 and REST/NRSF expression.  

PubMed

Nine neurodegenerative disorders are caused by CAG/polyglutamine (polyQ) repeat expansions. The molecular mechanisms responsible for disease-specific neurodegeneration remain elusive. We developed an embryonic stem (ES) cell-based model to probe the role of polyQ tract expansion in neuronal degeneration. ES cells containing expanded CAG repeats in the hypoxanthine phosphoribosyltransferase (Hprt) gene develop features typical of CAG-mediated neuropathology, exhibit length-dependent decrease in survival, undergo aberrant neuronal differentiation as well as persistent Oct-4 and Repressor element-1 transcription factor/neuron restrictive silencer factor (REST/NRSF) expression. This novel model will allow analysis of the molecular pathogenesis of neuronal degeneration and can be used to rapidly screen therapeutic interventions for these fatal diseases. PMID:15121185

Lorincz, Matthew T; Detloff, Peter J; Albin, Roger L; O'Shea, K Sue

2004-05-01

191

Human oestrus  

PubMed Central

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

Gangestad, Steven W; Thornhill, Randy

2008-01-01

192

Human Rhinoviruses  

PubMed Central

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

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

2013-01-01

193

Human Factors in Human-Systems Integration  

NASA Technical Reports Server (NTRS)

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.

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

2008-01-01

194

HUMAN RIGHTS IN SPORTS  

Microsoft Academic Search

This article, inspired by the activities surrounding the 50th anniversary of the Universal Declaration of Human Rights, examines both the development and potential of human rights initiatives in sports. Following a general discussion of the development and status of human rights, we turn specifically to the issue of human rights in sports, both in terms of the human rights of

Bruce Kidd; Peter Donnelly

2000-01-01

195

Human Papillomavirus (HPV)  

MedlinePLUS

... Preventable Diseases > Human Papillomavirus (HPV) Health Issues Listen Human Papillomavirus (HPV) Article Body According to the Centers ... Control and Prevention, there is an epidemic of human papillomavirus (HPV) in the United States. HPV is ...

196

Humanized Mouse Models to Study Human Diseases  

PubMed Central

Purpose of review Update on humanized mouse models and their use in biomedical research. Recent findings The recent description of immunodeficient mice bearing a mutated IL-2 receptor gamma chain (IL2ry) facilitated greatly the engraftment and function of human hematolymphoid cells and other cells and tissues. These mice permit the development of human immune systems, including functional T and B cells, following engraftment of hematopoietic stem cells (HSC). The engrafted functional human immune systems are capable of T and B cell-dependent immune responses, antibody production, anti-viral responses, and allograft rejection. Immunodeficient IL2rynull mice also support heightened engraftment of primary human cancers and malignant progenitor cells, permitting in vivo investigation of pathogenesis and function. In addition, human-specific infectious agents for which animal models were previously unavailable can now be studied in vivo using these new generation humanized mice. Summary Immunodeficient mice bearing an IL2rynull mutated gene can be engrafted with functional human cells and tissues, including human immune systems, following engraftment with human hematolymphoid cells. These mice are now used as in vivo models to study human hematopoiesis, immunity, regeneration, stem cell function, cancer, and human-specific infectious agents without putting patients at risk. PMID:20150806

Brehm, Michael A.; Shultz, Leonard D.; Greiner, Dale L.

2010-01-01

197

Human-machine interactions  

SciTech Connect

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.

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

198

Engineered human vaccines  

SciTech Connect

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.

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

1994-01-01

199

Human Research Protection Program Plan  

E-print Network

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

Weber, David J.

200

The Humanities: Interconnections.  

ERIC Educational Resources Information Center

Focusing on a wide range of interdisciplinary themes and ideas for humanities instruction, the 17 articles in this journal issue discuss the following topics: (1) literature, humanities, and the adult learner; (2) the role of the humanities in educating for a democracy; (3) humanities in the marketplace; (4) literature versus "great books" in high…

Salomone, Ronald E., Ed.

1985-01-01

201

Human Research Program Opportunities  

NASA Technical Reports Server (NTRS)

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.

Kundrot, Craig E.

2014-01-01

202

Humanities 1 Department of  

E-print Network

Humanities 1 Department of --Humanities This publication refers to the session 2009 of postgraduate opportunities go to www.imperial.ac.uk/pgprospectus. #12;2 Undergraduate syllabuses Humanities Teaching in Humanities at Imperial College London at undergraduate level is focused on service modules

203

Human Computer Intelligent Interaction  

E-print Network

Human Computer Intelligent Interaction Computer technologies are progressing at a breakneck speed human-computer interfaces.In this talk,I shall describe some of the research my students and I have been doing during the last decade on Human Computer Interaction. Specifically,information flow from human

Chen, Sheng-Wei

204

human spaceflight and operations  

E-print Network

1 human spaceflight and operations Lunar Lander human spaceflight and operations #12;2 human spaceflight and operations Lunar Lander Mission Objective Astronaut health Resources e.g. water, O, OH cooperation in exploration prim ary objective opportunity for investigations #12;3 human spaceflight

Anand, Mahesh

205

Preference for human eyes in human infants.  

PubMed

Despite evidence supporting an early attraction to human faces, the nature of the face representation in neonates and its development during the first year after birth remain poorly understood. One suggestion is that an early preference for human faces reflects an attraction toward human eyes because human eyes are distinctive compared with other animals. In accord with this proposal, prior empirical studies have demonstrated the importance of the eye region in face processing in adults and infants. However, an attraction for the human eye has never been shown directly in infants. The current study aimed to investigate whether an attraction for human eyes would be present in newborns and older infants. With the use of a preferential looking time paradigm, newborns and 3-, 6-, 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman primate faces (chimpanzees and Barbary macaques) that differed only by the eyes, thereby pairing a face with original nonhuman primate eyes with the same face in which the eyes were replaced by human eyes. Our results revealed that no preference was observed in newborns, but a preference for nonhuman primate faces with human eyes emerged from 3months of age and remained stable thereafter. The findings are discussed in terms of how a preference for human eyes may emerge during the first few months after birth. PMID:24581972

Dupierrix, Eve; de Boisferon, Anne Hillairet; Méary, David; Lee, Kang; Quinn, Paul C; Di Giorgio, Elisa; Simion, Francesca; Tomonaga, Masaki; Pascalis, Olivier

2014-07-01

206

Electrophilic Aromatic Selenylation: New OPRT Inhibitors  

PubMed Central

2-Ethoxyethaneseleninic acid reacts with electron rich aromatic substrates to deliver, by way of the selenoxides, the (2-ethoxyethyl) seleno ethers, which can in turn be transformed into a diverse set of aryl selenylated products. Among these, a family of 5-uridinyl derivatives shows sub-micromolar inhibition of human and malarial orotate phosphoribosyltransferase. PMID:20521773

Abdo, Mohannad; Zhang, Yong; Schramm, Vern L.; Knapp, Spencer

2010-01-01

207

Mice with human livers.  

PubMed

Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections. PMID:24042096

Grompe, Markus; Strom, Stephen

2013-12-01

208

Virtual Human Project  

SciTech Connect

This paper describes the development of a comprehensive human modeling environment, the Virtual Human, which will be used initially to model the human respiratory system for purposes of predicting pulmonary disease or injury using lung sounds. The details of the computational environment, including the development of a Virtual Human Thorax, a database for storing models, model parameters, and experimental data, and a Virtual Human web interface are outlined. Preliminary progress in developing this environment will be presented. A separate paper at the conference describes the modeling of sound generation using computational fluid dynamics and the modeling of sound propagation in the human respiratory system.

Ward, RD

2001-06-12

209

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.

210

Human Melioidosis, Malawi, 2011  

PubMed Central

A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing. PMID:23735189

Katangwe, Thembi; Purcell, Janet; Bar-Zeev, Naor; Denis, Brigitte; Montgomery, Jacqui; Alaerts, Maaike; Heyderman, Robert Simon; Dance, David A.B.; Kennedy, Neil; Feasey, Nicholas

2013-01-01

211

Mining human antibody repertoires  

PubMed Central

Human monoclonal antibodies (mAbs) have become drugs of choice for the management of an increasing number of human diseases. Human antibody repertoires provide a rich source for human mAbs. Here we review the characteristics of natural and non-natural human antibody repertoires and their mining with non-combinatorial and combinatorial strategies. In particular, we discuss the selection of human mAbs from naïve, immune, transgenic and synthetic human antibody repertoires using methods based on hybridoma technology, clonal expansion of peripheral B cells, single-cell PCR, phage display, yeast display and mammalian cell display. Our reliance on different strategies is shifting as we gain experience and refine methods to the efficient generation of human mAbs with superior pharmacokinetic and pharmacodynamic properties. PMID:20505349

2010-01-01

212

Introduction Letters/Humanities  

E-print Network

Cognitive Studies Psychology Linguistics Art Theory Social Culture Sociology Art History Geography Doctoral and American Literature European Literature Human Social Dynamics History Cognitive Studies Socio abilities to create literature and arts? What really are human cognitive mechanisms and languages, which

Banbara, Mutsunori

213

Climate and Human Evolution  

NSDL National Science Digital Library

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.

Foundation, Wgbh E.

2010-11-30

214

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.

215

Programming with human computation  

E-print Network

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 ...

Little, Greg (Danny Greg)

2011-01-01

216

Pathfinder: Humans in space  

NASA Technical Reports Server (NTRS)

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

Anderson, John L.

1988-01-01

217

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.

218

Human Parainfluenza Viruses  

MedlinePLUS

... visit this page: About CDC.gov . Human Parainfluenza Viruses (HPIVs) Human parainfluenza viruses (HPIVs) commonly cause respiratory ... HPIVs Are Not the Same as Influenza (Flu) Viruses People usually get HPIV infections in the spring, ...

219

HPV (Human Papillomavirus)  

MedlinePLUS

... papillomavirus test for primary cervical cancer screening HPV (human papillomavirus) Print and Share (PDF 1105 KB ) En Español HPV (human papillomavirus) is a sexually transmitted virus. It is passed ...

220

Human productivity program definition  

NASA Technical Reports Server (NTRS)

The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

Cramer, D. B.

1985-01-01

221

Human Model Report  

Microsoft Academic Search

12 pages\\u000aProvider Notes:This page contains the human model report.Last update 11\\/21\\/2005. In the order of importance, human needs oxygen, water and food for survival. Human produces energy, carbon dioxide, sweat, urine, and feces. These inputs and outputs contents and quantity are depended on human consumption and body structures such as gender, age, and body mass. Environment is a very

ALS-NSCORT

2005-01-01

222

The Human Body  

NSDL National Science Digital Library

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 ...

Bratkiewicz, Miss

2011-12-10

223

Human factors in mining  

SciTech Connect

This Bureau of Mines report is directed toward summarizing the application of human factors to improving safety, productivity, and the general physical and psychological working conditions of miners and toward familiarizing readers with the role of human factors in the mining industry and the benefits that car accrue by systematically applying human factors principles and data.

Sanders, M.S.; Peay, J.M.

1988-01-01

224

Humanity's unsustainable environmental footprint  

E-print Network

) and resultant impacts (such as biodiversity loss or effects on human health or economy). Environmental (BF)mea- sures the threat of human activity to biodiversity (14). Footprints are indicators of human this pressure (such as land-use changes, land degradation, reduced river flows, water pollution, climate change

Napp, Nils

225

Human Functional Brain Imaging  

E-print Network

Human Functional Brain Imaging 1990­2009 September 2011 Portfolio Review #12;2 | Portfolio Review: Human Functional Brain ImagingThe Wellcome Trust is a charity registered in England and Wales, no's role in supporting human functional brain imaging and have informed `our' speculations for the future

Rambaut, Andrew

226

Human Rights and Security  

E-print Network

Migration, Human Rights and Security in Europe MRU Student Conference Proceedings 2012 Edited by Siril Berglund, Helen McCarthy and Agata Patyna #12;2 "Migration, Human Rights and Security...............................................................................................58 #12;3 "Migration, Human Rights and Security in Europe", MRU Student Conference Proceedings

Jones, Peter JS

227

Developments in Human Communication  

E-print Network

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

Haykin, Simon

228

Production Of Human Antibodies  

NASA Technical Reports Server (NTRS)

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.

Sammons, David W.; Neil, Garry A.

1993-01-01

229

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...

230

Esprit: A Humanities Magazine.  

ERIC Educational Resources Information Center

In March 1984, the first issue of "Esprit," a semi-annual humanities magazine for the 56 two-year colleges in New York State, was published. The magazine seeks to confront the apparent decline of student interest in the humanities, community doubts about the relevance of the humanities, and the seeming indifference to the special truths inherent…

Parker, Donald G.; Capella, Barry John

231

Whose Human Rights?  

ERIC Educational Resources Information Center

During the last 50 years, principles, institutions, and policies of human rights have been developed worldwide. This book brings together European and international conventions on human rights, the rights of women, and the users and uses of education, and places them in their wider context. It examines issues in how human rights work, the ways in…

Rendel, Margherita

232

Human Tail and Myelomeningocele  

Microsoft Academic Search

The human tail is rarely reported and is usually associated with underlying spina bifida occulta. A male newborn presenting a caudal appendage (human tail) with skin-covered myelomeningocele and tethered cord is described. Surgical excision of the human tail and repair of the myelomeningocele were performed 3 days after birth. After the operation, the patient had an uneventful convalescence and received

Pei-Jung Lin; Yu-Tang Chang; Hsing-I Tseng; Jan-You Lin; Yu-Sheng Huang

2007-01-01

233

Are humans resources?  

Microsoft Academic Search

Purpose – This paper aims to offer a critique, from a career studies perspective, of the common term “human resource management.” Design\\/methodology\\/approach – Provides a literature review and critique. Findings – The term “human resource management” is a metaphor that presents employees as passive commodities or assets rather than as active agents, and thereby potentially de-humanizes them. In an alternative

Kerr Inkson

2008-01-01

234

Humanities 4 Professor Watkins  

E-print Network

Humanities 4 Professor Watkins Winter 2013 Writing Assignment No. 1 Essays are due at the beginning) in the Humanities format* and a counterargument is required. Respond to one of the following prompts: 1. Write in a manila folder with your name on it and containing your previous Humanities essays. Late essays

Blanco, Philip R.

235

Humanities 1 Professor Edwards  

E-print Network

Humanities 1 Professor Edwards Winter 2013 Writing Exercise Assignments are due at the end of lecture on Wednesday, January 16th . They should be 1-2 pages in length in the Humanities format (see in a plain manila folder with your name on it. All Humanities essays are to be saved and turned in each time

Blanco, Philip R.

236

Indigenous human rights  

Microsoft Academic Search

Indigenous Human Rights is an edited selection of proceedings of the Australian Indigenous Human Rights Conference, organised by members of Southern Cross University in February 2000. The collection covers a range of issues relating to Indigenous human rights including: racial discrimination and 'special measures'; removal of children; law and order; access to the United Nations; and prospects for the use

Sam Boris Garkawe; Loretta Kelly; Warwick Fisher

2001-01-01

237

integration division Human Systems  

E-print Network

integration division Human Systems Eye-Movement Metrics: Non-Intrusive Quantitative Tools a r c h C e n t e r - C a l i f o r n i a , U S A To simultaneously measure eye movements and human-based predictions of human performance accuracy from the eye-movement data with actual performance under rigorously

238

Human Genetics Portfolio Review  

E-print Network

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

Rambaut, Andrew

239

Human Research ProgramHuman Research Program Human System Risk in Exploration and  

E-print Network

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

Waliser, Duane E.

240

Human research subjects as human research workers.  

PubMed

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

Lynch, Holly Fernandez

2014-01-01

241

Human Performance in Space  

NASA Technical Reports Server (NTRS)

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.

Jones, Patricia M.; Fiedler, Edna

2010-01-01

242

Laterality and Human Evolution  

Microsoft Academic Search

The question of whether there is a fundamental discontinuity between humans and other primates is discussed in relation to the predominantly human pattern of right-handedness and the left-cerebral representation of language. Both phenomena may go back at least to Homo habilis, 2–3 million years ago. However, a distinctively human mode of cognitive representation may not have emerged until later, beginning

Michael C. Corballis

1989-01-01

243

Annotated Webliography Of Humanism  

NSDL National Science Digital Library

Created and maintained by Peter Derkx, a professor of history at the University for Humanist Studies, this Website offers a useful directory of annotated links on the subject of humanism from its inception in the Renaissance to its current struggles with Marxism and Postmodernism. The selections when addressing more contemporary topics often deal with humanism only indirectly -- a sign perhaps of the failing interest in humanism per se, rather than any lack of diligence on Dr. Derkx' part.

Derkx, Peter.

1998-01-01

244

Fully Modern Humans  

Microsoft Academic Search

For decades paleoanthropologists have pondered whether modern humans evolved throughout the human geographic range or in only\\u000a a small part. Debate continues, but the accumulating fossil, archaeological, and genetic evidence increasingly points to a\\u000a restricted origin in Africa from which modern humans spread to replace or swamp their nonmodern contemporaries elsewhere.\\u000a The case is particularly clear with regard to the

Richard G. Klein

245

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.

246

Sustaining humans in space.  

PubMed

One goal of NASA's Ames Research Center is to extend the presence of humans in space. Biomedical research, human performance, and life-support systems form the core of the Ames program. Major questions highlight how the effects of microgravity on living systems are modified by exercise, artificial gravity, autogenic feedback training, and nutrition. Bioengineering and life science studies include humans, animals, and plants. Ames investigators collaborate extensively with outside university and commercial scientists, both within the United States and internationally. PMID:11539815

Hubbard, G S; Hargens, A R

1989-09-01

247

Neandertal vs. Modern Human  

E-print Network

human skeletal remains. The opposing side to this argument is the Multiregional Evolution model. This model differs from the first by denying a recent African origin for modern humans and instead emphasizes the role of both genetic continuity over...73 INTRODUCTION Since the initial discovery of Neandertals there has been an ongoing debate about their phylogenetic position in evolution. Are they or are they not a separate species from the modern human? In the past, Paleoanthropologists...

Hill, Brittany

2009-10-01

248

Human target acquisition performance  

NASA Astrophysics Data System (ADS)

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.

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

249

Reflecting on Human Reflexes  

NSDL National Science Digital Library

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.

GK-12 Program, Computational Neurobiology Center,

250

Human-Web Interactions  

NASA Astrophysics Data System (ADS)

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.

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

251

Human factors: Aeronautics  

NASA Technical Reports Server (NTRS)

The objectives of the Aeronautics Human Factors Research and Technology program are to provide the technology base and capability to design effective crew-cockpit systems and to advance solutions to human problems affecting air transport and rotorcraft effectiveness and safety. Advanced automation technologies, information display capabilities under computer control, and concern for the effects of human error in flight operations are elements which drive the directions of the program. Thus, the program has four thrusts: flight management, human engineering methods, rotorcraft, and subsonic transports.

Jenkins, James P.

1988-01-01

252

Robotics for Human Exploration  

NASA Technical Reports Server (NTRS)

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.

Fong, Terrence; Deans, Mathew; Bualat, Maria

2013-01-01

253

Department of Humanities Department of Humanities  

E-print Network

are aesthetics; document and online design; ethics in the professions; history of art and architecture of Humanities Writing Center, and Associate Director for ESL Programs. B.A., M.S., Indiana University. Davis College; Ph.D., Loyola University of Chicago. Glassman, Ellen C., Senior Lecturer of Art and Architectural

Heller, Barbara

254

HUMAN DIGNITY AND HUMAN REPRODUCTIVE CLONING  

Microsoft Academic Search

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

Steven Malby

2002-01-01

255

Human Development, Human Differences and Learning.  

ERIC Educational Resources Information Center

This module (part of a series of 24 modules) is on human development, student characteristics, and learning styles. The genesis of these materials is in the 10 "clusters of capabilities," outlined in the paper, "A Common Body of Practice for Teachers: The Challenge of Public Law 94-142 to Teacher Education." These clusters form the proposed core…

Dillon, Ronna F.

256

Introduction Human Development/Human Devel-  

E-print Network

interdisciplinary approaches: developmental psychology, clinical psychology, health sciences, education and learning Science of Education Human Behavior Health Promotion and Education Behavioral Development Sport Sciences people to carry out those tasks will become more and more important. It is essential to enhance literacy

Banbara, Mutsunori

257

The Human Serum Metabolome  

Microsoft Academic Search

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

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

2011-01-01

258

Assessment of Human Factors  

NASA Technical Reports Server (NTRS)

Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

Mount, Frances; Foley, Tico

1999-01-01

259

Human Evolution Developmental Change  

E-print Network

Human Evolution through Developmental Change Edited by Nancy Minugh-Purvis and Kenneth J. Mc (p. ) and index, ISB:" 0-8018-6732-0 (h'lrdeo\\'er) 1. Human evolution. 2, Heterochrony (Biolog:-l. 3 forms. More recently, it has been argued that, on the contrary, many aspects ofhominid evolution reflect

Lee, Dongwon

260

Human Functional Brain Imaging  

E-print Network

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

Rambaut, Andrew

261

Humane Education Projects Handbook.  

ERIC Educational Resources Information Center

This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

Junior League of Ogden, UT.

262

Television's new humane collectivity  

Microsoft Academic Search

Analysis of the manifest content of Taxi, Barney Miller, Lou Grant, and M*A*S*H reveals three predominant fantasy themes: the realization of significant others, the alliance in action, and membership into personhood. From these three themes emerges a rhetorical vision, the new humane collectivity, which focuses on a meaningful and rewarding existence based on humane, sympathetic awareness of and concern for

Robert L. Schrag; Richard A. Hudson; Lawrance M. Bernabo

1981-01-01

263

Introduction to Human Genetics  

NSDL National Science Digital Library

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.

BEGIN:VCARD VERSION:2.1 FN:Sharon Nelson N:Nelson;Sharon ORG:Waunakee High School REV:2005-04-11 END:VCARD

1995-06-30

264

The “Practice of Humanity  

Microsoft Academic Search

“Practice of Humanity” examines visual and legal representations of transnational sex and domestic work. Specifically, we analyze a 2003 United Nations public service announcement, Cleaning Lady; the 2000 UN Protocol on Human Trafficking; the 2000 US Victims of Trafficking and Violence Protection Act; and current trends in the sociological literatures of both types of work. We demonstrate how these texts

Julietta Hua; Kasturi Ray

2010-01-01

265

Human Resources Policy Guidelines  

E-print Network

Human Resources Policy Guidelines Your Guide to Human Resources Policies at Rensselaer Polytechnic . . . . . . . 100-8 200 Recruitment and Selection 200.1 Performance Management Tool . . . . . 200-1 200.2 Position.4 Recruitment for Staff Positions. . . . . . 200-7 200.5 Hiring for Staff Positions . . . . . . 200-9 200

Linhardt, Robert J.

266

Human Sociobiology: Wilson's Fallacy.  

ERIC Educational Resources Information Center

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…

Lehrman, Nathaniel S.

1981-01-01

267

Human Service Programs  

Microsoft Academic Search

Suggests that H. C. Schulberg's comments on human service programs for psychologists underline a major problem of society and confront the psychological profession with the demand for assistance in human caretaking. It is recommended that schools be given prime consideration in a community mental health context.

Hanna Bauer

1973-01-01

268

Introduction to human services  

Microsoft Academic Search

This book delivers a uniquely practical and comprehensive introduction to the human service profession. Drawing on the authors' extensive experience as practitioners, educators, and researchers, this best-selling text defines human services, reviews the historical development of the field, and provides a practical overview of the profession. It thoroughly explores the current state of this rapidly evolving profession as well as

Tricia McClam; Marianne R Woodside

2012-01-01

269

Aging and Human Performance  

Microsoft Academic Search

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

Neil Charness

2008-01-01

270

Crosstalk in Humanities Computing  

Microsoft Academic Search

We would like to stimulate crosstalk among the humanities in this paper, i. e., interdisciplinary investigation, and more speci cally to show how hu-manities computing might stimulate this. We use the subjects of cultural variation and cultural di usion to underscore our main argument that such crosstalk might take place at a more fruitful level than earlier, noting rst, that

JOHN NERBONNE

2007-01-01

271

integration division Human Systems  

E-print Network

Vibration Test Facility incorporates state-of-the-art vibration generation and measurement hardwareintegration division Human Systems ISIS Vibration Test Facility Objective Approach Impact 1. Assess impact of flight-like whole-body vibration on human operational capabilities and ability to maintain

272

HUMAN HEALTH RESEARCH STRATEGY  

EPA Science Inventory

The mission of the U.S. Environmental Protection Agency (EPA) is to protect public health and safeguard the environment. Risk assessment is an integral part of this mission in that it identifies and characterizes environmentally related human health problems. The Human Health Re...

273

The human sialyltransferase family  

Microsoft Academic Search

The human genome encodes probably more than 20 different sialyltransferases involved in the biosynthesis of sialylated glycoproteins and glycolipids but to date only 15 different human sialyltransferase cDNAs have been cloned and characterized. Each of the sialyltransferase genes is differentially expressed in a tissue-, cell type-, and stage-specific manner to regulate the sialylation pattern of cells. These enzymes differ in

Anne Harduin-Lepers; Veronica Vallejo-Ruiz; Marie-Ange Krzewinski-Recchi; Bénédicte Samyn-Petit; Sylvain Julien; Philippe Delannoy

2001-01-01

274

Predictors of human rotation  

Microsoft Academic Search

Why some humans prefer to rotate clockwise rather than anticlockwise is not well understood. This study aims to identify the predictors of the preferred rotation direction in humans. The variables hypothesised to influence rotation preference include handedness, footedness, sex, brain hemisphere lateralisation, and the Coriolis effect (which results from geospatial location on the Earth). An online questionnaire allowed us to

Jan Stochl; Tim Croudace

2012-01-01

275

Human Embryology & Developmental Biology  

E-print Network

Biology is the modern synthesis of biological and medical sciences that looks at how the tissuesBSc (Hons) Human Embryology & Developmental Biology DEGREE PROGRAMME GUIDE 2013-2014 #12;BSc (Hons) Human Embryology & Developmental Biology Introduction Degree Aims and Outcomes General Enquiries

Levi, Ran

276

Human vaccines & immunotherapeutics: news.  

PubMed

Infant rotavirus vaccination provides for herd immunity Nonreplicating sporozoite vaccine protects humans against malaria Personalized brain cancer vaccine enters phase 2 trial Novel implantable therapeutic cancer vaccine to be tested in humans Clostridium difficile vaccine candidate successful in phase 1 CDC reports strong uptake of HPV vaccine in boys Whooping cough outbreak in Texas. PMID:24056006

Riedmann, Eva M

2013-10-01

277

Human Granulocytic Anaplasmosis, Japan  

PubMed Central

We retrospectively confirmed 2 cases of human Anaplasma phagocytophilum infection. Patient blood samples contained unique p44/msp2 for the pathogen, and antibodies bound to A. phagocytophilum antigens propagated in THP-1 rather than HL60 cells. Unless both cell lines are used for serodiagnosis of rickettsiosis-like infections, cases of human granulocytic anaplasmosis could go undetected. PMID:23460988

Gaowa; Wuritu; Kawamori, Fumihiko; Wu, Dongxing; Yoshikawa, Yuko; Chiya, Seizou; Fukunaga, Kazutoshi; Funato, Toyohiko; Shiojiri, Masaaki; Nakajima, Hideki; Hamauzu, Yoshiji; Takano, Ai; Kawabata, Hiroki; Ando, Shuji; Kishimoto, Toshio

2013-01-01

278

WORKPLACE VIOLENCE HUMAN RESOURCES  

E-print Network

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 that is free from intimidation, acts and/or threats of violence against life, health, well-being, and

Su, Xiao

279

Human papillomavirus in men - \\  

Microsoft Academic Search

The objective of this review was to discuss viral infection by Human papillomavirus because of its elevated incidence among women and their respective partners, as well as the relation between the virus groups found in women with cervical intraepithelial neoplasia or normal women and their respective partners. The presence of human papillomavirus in male partners does not necessarily implicate the

Charles Rosenblatt; Antonio Marmo Lucon; Elza Ainda; Gay Pereyra; José Aristodemo Pinnotti; Sami Arap

280

Human gene therapy.  

PubMed

Human gene therapy is a procedure that is being used in an attempt to treat genetic and other diseases. Eleven clinical protocols are under way at the present time, each with scientific and clinical objectives. Human genetic engineering raises unique safety, social, and ethical concerns. PMID:1589762

Anderson, W F

1992-05-01

281

ESA Human Exploration Activities  

Microsoft Academic Search

The long term goal of the Aurora Exploration Programme is Human exploration of Mars. In preparation for this, exploration of the Moon is a necessary step to provide demonstration of capabilities, mandatory for long duration human spaceflight. With the European Columbus module attached to the ISS, Europe has access to a world class laboratory in space for microgravity research, technology

Scott Hovland

2008-01-01

282

Mars Human Exploration Objectives  

Microsoft Academic Search

This paper reviews the objectives and other considerations of Human exploration of Mars. The objectives of human exploration of Mars are: (1) to learn how Mars is similar to, and different from, Earth; (2) to explore possible life, past and present; (3) to discover what Mars is like now from the perspective of Geoscience and geologic history; and (4) how

Geoff Briggs

1998-01-01

283

Human Simulated Diving Experiments.  

ERIC Educational Resources Information Center

This report details several simulated divinq experiments on the human. These are suitable for undergraduate or graduate laboratories in human or environmental physiology. The experiment demonstrates that a diving reflex is precipitated by both facial cooling and apnea. (Author/RE)

Bruce, David S.; Speck, Dexter F.

1979-01-01

284

Pollution and human biology.  

PubMed

Industrial pollution is a relatively new component of the environment of humans and may constitute biological challenges to human adaptation. Extensive laboratory research shows that many pollutants are capable of modifying physiological systems in mammals. Studies of human populations provide substantial evidence that some pollutants can affect biological outcomes of traditional interest to human biologists (e.g. mortality, morbidity, growth, reproduction). Air pollution has been linked to increases in mortality and morbidity, and specific pollutants such as lead and persistent organic pollutants (POPs) have been associated with decreases in measures of sperm quality, changes in the character of menses, increased obesity and diabetes, and altered rates of sexual maturation, as well as other effects. However, the evidence is far from homogeneous. Nevertheless, to achieve the comprehensive and holistic approach characteristic of human biological research, investigators should include measures of pollutant exposure in their multicausal models. PMID:20412024

Schell, Lawrence M; Burnitz, Kristopher K; Lathrop, Patrick W

2010-06-01

285

Beliefs about Human Extinction  

SciTech Connect

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.

Tonn, Bruce Edward [ORNL

2009-11-01

286

Mars Human Exploration Objectives  

NASA Technical Reports Server (NTRS)

This paper reviews the objectives and other considerations of Human exploration of Mars. The objectives of human exploration of Mars are: (1) to learn how Mars is similar to, and different from, Earth; (2) to explore possible life, past and present; (3) to discover what Mars is like now from the perspective of Geoscience and geologic history; and (4) how did Mars form and how did its formation differ from Earth. Considerations of human Martian exploration involve: (1) having a capable base laboratory; (2) having long range transportation; (3) having operational autonomy of the crew, and the requirement of the crew to possess a range of new cognitive processes along with easy communications with terrestrial colleagues; and finally (4) creating the human habitat along with human factors which involve more than just survivability.

Briggs, Geoff

1998-01-01

287

Human Space Flight  

NASA Technical Reports Server (NTRS)

The first human space flight, in the early 1960s, was aimed primarily at determining whether humans could indeed survive and function in micro-gravity. Would eating and sleeping be possible? What mental and physical tasks could be performed? Subsequent programs increased the complexity of the tasks the crew performed. Table 1 summarizes the history of U.S. space flight, showing the projects, their dates, crew sizes, and mission durations. With over forty years of experience with human space flight, the emphasis now is on how to design space vehicles, habitats, and missions to produce the greatest returns to human knowledge. What are the roles of the humans in space flight in low earth orbit, on the moon, and in exploring Mars?

Woolford, Barbara; Mount, Frances

2004-01-01

288

Archaea on human skin.  

PubMed

The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin. PMID:23776475

Probst, Alexander J; Auerbach, Anna K; Moissl-Eichinger, Christine

2013-01-01

289

Human Space Exploration  

NASA Technical Reports Server (NTRS)

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.

Jeevarajan, Antony

2014-01-01

290

[On bedside medical humanities].  

PubMed

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

Barilan, M; Sharon, D

2001-12-01

291

Human Gyrovirus DNA in Human Blood, Italy  

PubMed Central

Human gyrovirus (HGyV) is a recent addition to the list of agents found in humans. Prevalence, biologic properties, and clinical associations of this novel virus are still incompletely understood. We used qualitative PCRs to detect HGyV in blood samples of 301 persons from Italy. HGyV genome was detected in 3 of 100 solid organ transplant recipients and in 1 HIV-infected person. The virus was not detected in plasma samples from healthy persons. Furthermore, during observation, persons for whom longitudinal plasma samples were obtained had transient and scattered presence of circulating HGyV. Sequencing of a 138-bp fragment showed nucleotide identity among all the HGyV isolates. These results show that HGyV can be present in the blood of infected persons. Additional studies are needed to investigate possible clinical implications. PMID:22608195

Macera, Lisa; Focosi, Daniele; Vatteroni, Maria Linda; Boggi, Ugo; Antonelli, Guido; Eloit, Marc; Pistello, Mauro

2012-01-01

292

Human Rights Watch: Defending Human Rights Worldwide  

NSDL National Science Digital Library

The Human Rights Watch (HRW) is an independent, international nongovernmental organization with offices in 21 cities around the world (and field posts in 20 additional countries). Founded in 1978, HRW seeks to enforce fair treatment of all citizens, regardless of country, through investigation and publication of abuses. Each year, the group puts out a comprehensive World Report, which can be downloaded from the web site free of charge. The 2014 report features updates on dozens of countries, as well as analyses of themes such as The Human Rights Case for Drug Reform. For an overview of this essential document, read the Keynote, delivered by Kenneth Roth. Links to Essays, Photos and Videos, and Publications take the reader deeper into the HRWâÂÂs recent findings.

2014-01-01

293

Redrawing Humanity's Family Tree  

NSDL National Science Digital Library

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.

Wilford, John N.

1969-12-31

294

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.

1998-01-01

295

HUMAN BIOLOGY Understanding normal and disordered human function both require a broad integration of human  

E-print Network

HUMAN BIOLOGY Understanding normal and disordered human function both require a broad integration sciences focus on the relevance of these areas to the human condition. Given the focus on human biology IN HUMAN BIOLOGY School Requirements: Biological Sciences 2A, 194S; Biological Sciences Core 93, 94, 97, 98

Rose, Michael R.

296

POSITION DESCRIPTIONS GUIDELINE HUMAN RESOURCES  

E-print Network

and activities related to successful human resources operations such as: recruitment and selection, jobPOSITION DESCRIPTIONS GUIDELINE HUMAN RESOURCES Equal Opportunity & Workforce Planning | One and management position descriptions are available online at the Human Resources All Forms page website

Su, Xiao

297

HUMAN GROSS ANATOMY ANTH 695  

E-print Network

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

Auerbach, Benjamin M.

298

Strategic Implications of Human Trafficking.  

National Technical Information Service (NTIS)

There is a problem known as human trafficking that could have a direct effect on America's national security. Human trafficking involves various forms of human enslavement for prostitution and other forms of exploitation, including false promises of jobs ...

D. D. Watkins

2005-01-01

299

Human Resources Simon Fraser University  

E-print Network

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

Kavanagh, Karen L.

300

Office for Human Research Protections  

MedlinePLUS

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

301

HUMAN SUBJECT PAYMENTS Policy Statement  

E-print Network

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

Shahriar, Selim

302

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

303

Special Issue on Human Computing  

E-print Network

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.

Nijholt, Anton

304

HUMAN SERVICES Mental Health Services  

E-print Network

procedures. Federal government, Departments of Health and Human Services Justice Veterans AdministrationPSYCHOLOGY HUMAN SERVICES Counseling Advocacy Mental Health Services STRATEGIESAREAS EMPLOYERS State government, Departments of Human Services Mental Health & Mental Retardation Community mental

Escher, Christine

305

Human Resources August 2008  

E-print Network

Human Resources 1st August 2008 Updated November 2011 RELOCATION ASSISTANCE SCHEME #12;2 Contents 1........................................................................ 5 7. Cost of Removal of Personal and Household Effects .......................................... 5 8. Cost of Property Sale and/or Purchase

Doran, Simon J.

306

Aerospace Human Factors  

NASA Technical Reports Server (NTRS)

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.

Jordan, Kevin

1999-01-01

307

Human Reliability Program Overview  

SciTech Connect

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.

Bodin, Michael

2012-09-25

308

Statement on Human Cloning  

MedlinePLUS

Home American Association for the Advancement of Science Statement on Human Cloning Tweet Email Print The American Association for the Advancement of Science (AAAS) recognizes the intense debates within our society ...

309

Introduction Letters/Humanities  

E-print Network

Literature Japanese Language and Literature Chinese Language and Literature British and American Literature German Literature French Literature History Japanese History Asian History European and American History British and American Literature European Literature Human Social Dynamics History Cognitive Studies Socio

Banbara, Mutsunori

310

The Human Hazard.  

ERIC Educational Resources Information Center

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)

Tickell, Crispin

1995-01-01

311

Approaches to Human Communication.  

ERIC Educational Resources Information Center

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…

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

312

What makes us human?  

E-print Network

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.

Mikkelsen, Tarjei S.

313

Human intelligible positioning  

E-print Network

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 ...

Venugopalan, Vishwanath, 1981-

2004-01-01

314

Patenting Human Evolution  

E-print Network

the potential to promote the kinds of genetic enhancements that might lead to human evolutionary change. Public policy and the law must grapple with the implications of genetic enhancement before current technological possibilities become societal realities...

Torrance, Andrew W.

2008-06-01

315

Human Computers 1947  

NASA Technical Reports Server (NTRS)

Langley's human computers at work in 1947. The female presence at Langley, who performed mathematical computations for male staff. Photograph published in Winds of Change, 75th Anniversary NASA publication (page 48), by James Schultz.

1947-01-01

316

Teaching about Human Geography.  

ERIC Educational Resources Information Center

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)

Schlene, Vickie J.

1991-01-01

317

HUMAN DEVELOPMENT GRADUATE GROUP  

E-print Network

Program Coordinator: Effie Kolbeins Faculty Program Advisors: Zhe Chen Katherine Conger Larry Harper RoseHUMAN DEVELOPMENT GRADUATE GROUP PH.D. STUDENT HANDBOOK 2007 - 2008 Program Chair: L. V. Harper

Ullrich, Paul

318

Human Biomass Consumption  

NASA Video Gallery

Humans are using an increasing amount of Earthâ??s annual production of plants. Research shows that, from 1995 to 2005, consumption rose from 20 to 25 percent of the planet's annual production. Wha...

319

Human Papillomavirus (HPV) Screening  

MedlinePLUS

... message, please visit this page: About CDC.gov . Human Papillomavirus (HPV) Share Compartir Screening Cervical cancer is the easiest ... and then every three years after that. The HPV test checks for the virus that can cause ...

320

Human-centered Computing  

NASA Astrophysics Data System (ADS)

Computing is at one of itsmost excitingmoments in history, playing an essential role in supporting many important human activities. The explosion in the availability of information in various media forms and through multiple sensors and devices means, on one hand, that the amount of data we can collect will continue to increase dramatically, and, on the other hand, that we need to develop new paradigms to search, organize, and integrate such information to support all human activities.

Sebe, Nicu

321

Evolution and human sexuality.  

PubMed

The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory. PMID:24151100

Gray, Peter B

2013-12-01

322

Immunosenescence and human longevity  

Microsoft Academic Search

Humans are almost certainly the longest-living of all mammals. What explains their longevity? Are there evolutionary pressures\\u000a favouring longer life and if so what are they? If longevity is a positively selected trait, are many or few genes responsible\\u000a for this characteristic? It is proposed here that human longevity was selected for at the level of relatively few genes and

Graham Pawelec

2003-01-01

323

Research with human subjects.  

PubMed

Ackerman reviews three recent books on moral issues in human research: Who Goes First? The Story of Self-Experimentation in Medicine, by Lawrence K. Altman (Random House; 1987); The Patient as Partner: A Theory of Human-Experimentation Ethics, by Robert M. Veatch (Indiana University Press; 1987); and Ethics and Regulation of Clinical Research, 2d ed., by Robert J. Levine (Urban & Schwarzenberg; 1986). PMID:11653831

Ackerman, Terrence F

1988-01-01

324

Human rabies in Delhi  

Microsoft Academic Search

Objective : Analysis of human rabies cases admitted in Infectious Diseases Hospital, Delhi during the course of one year was undertaken\\u000a to understand the epidemiology of rabies.Methods : The data was collected using standardized proforma and was analyzed on EPI Info 6.02 software version. A total of 49.8%\\u000a of the human rabies came from Delhi and rest belonged to adjoining

Mala Chhabra; R. L. Ichhpujani; K. N. Tewari; Shiv Lal

2004-01-01

325

Human pulmonary dirofilariasis.  

PubMed

Dirofilaria immitis, the canine heartworm, is a relatively rare, but well-documented cause of human lung disease. The disease presents in man as a solitary, peripheral parenchymal lung nodule which may simulate a peripheral lung neoplasm. This case is the first report of the disease in New Zealand, a country where the parasite has not become established in the dog population. A brief review of the life cycle, epidemiology and clinical data relating to human dirofilariasis is included. PMID:6591027

Jagusch, M F; Roberts, R M; Rea, H H; Priestley, D R

1984-08-22

326

The human oncogenic viruses  

SciTech Connect

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.

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

1986-01-01

327

The Human Virome  

Microsoft Academic Search

\\u000a In this chapter we discuss changing approaches to viral discovery and human health, summarize the current understanding of\\u000a the human-associated viral community, and review contemporary methods in viral metagenomics. The virome is the community of viruses that populate an organism or ecosystem at any given time. This includes the “core” set of commensal viruses that do not give rise to

Matthew Haynes; Forest Rohwer

328

Cholesterol and Human Health  

Microsoft Academic Search

Cholesterol plays a major role in human heart health and high cholesterol is a leading risk factor for human cardiovascular disease such as coronary heart disease and stroke. There are 102.3 million American adults who have total blood cholesterol values of 200 mg\\/dl and higher, and about 41.3 million. Cholesterol can be good (high-density lipoprotein) or bad (low-density lipoprotein) to

Hongbao Ma

2006-01-01

329

Human neuronal nicotinic receptors  

Microsoft Academic Search

Nicotine is a very widely used drug of abuse, which exerts a number of neurovegetative, behavioural and psychological effects by interacting with neuronal nicotinic acetylcholine receptors (NAChRs). These receptors are distributed widely in human brain and ganglia, and form a family of ACh-gated ion channels of different subtypes, each of which has a specific pharmacology and physiology. As human NAChRs

C. Gotti; D. Fornasari; F. Clementi

1997-01-01

330

Urbanization and human rights  

Microsoft Academic Search

Urban governance on the basis of human rights can help to set up problem solving\\u000amechanisms to guarantee social peace, economic growth and political participation.If states both integrate more in international or regional human rights regime and give more autonomy to urban governments and local authorities, many of these issues of urbanization can be solved. Where people organize themselves on

A. Mihr

2010-01-01

331

Geology and Human Health  

NSDL National Science Digital Library

This site contains a variety of educational and supporting materials for faculty teaching in the emerging field of geology and human health. You will find links to internet resources, books, teaching activities, and a group email list, as well as posters, presentations and discussions from the spring 2004 workshop on Geology and Human Health. These resources reflect the contributions of faculty members from across the country and the collections will continue to grow as materials are developed.

332

Testing for Human Immunodeficiency Virus  

MedlinePLUS

Testing for Human Immunodeficiency Virus The American College of Obstetricians and Gynecologists Women’s Health Care Physicians patient education Fact Sheet PFS005: Testing for Human Immunodeficiency ...

333

Human Factors Review Plan  

SciTech Connect

''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.

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

1985-12-01

334

Human Development Report 2005  

NSDL National Science Digital Library

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 âÂÂcreating an environment in which people can develop their full potential and lead productive, creative lives in accord with their needs and interestsâÂÂ. 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.

2005-01-01

335

Developing Human Performance Measures  

SciTech Connect

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.

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

2006-05-01

336

Infants' Responses to Real Humans and Representations of Humans  

ERIC Educational Resources Information Center

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…

Heron, Michelle; Slaughter, Virginia

2010-01-01

337

HUMAN RESOURCE MANAGEMENT Human resource management is the process of  

E-print Network

5/2013 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 environment. The Human Resource Management program at Wichita State University prepares you to meet

338

Human Resource Development Bachelor of Science in Human Resource Development  

E-print Network

in Human Resource Development (Fall only) 3 MGMT 309 Survey of Management 3 FINC 409 Survey of FinanceHuman Resource Development Bachelor of Science in Human Resource Development FRESHMAN YEAR First. and Practices of Leadership in Human Resource Development 3 12 EHRD 491 Research 5,7 3 MKTG 409 Intro

Behmer, Spencer T.

339

The Human Condition: Medicine, Arts and Humanities Spring Quarter 2014  

E-print Network

The Human Condition: Medicine, Arts and Humanities INDE 212 Spring Quarter 2014 Thursdays from 2:15 to 4:05 This course is the Biomedical Ethics and Medical Humanities Scholarly Concentration gateway course for medical humanities. The course is open to all Stanford medical, graduate and undergraduate

Straight, Aaron

340

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

341

The Humanities and a Humanities Exploration Rodney Frey  

E-print Network

The Humanities and a Humanities Exploration Rodney Frey (from the keynote address given 12 September 2011) Now donning the regalia and dancing as the "distinguished humanities professorship" ­ though at my core still an ethnographer ­ this Humanities Exploration is really a year-long unfolding

O'Laughlin, Jay

342

Meeting human needs  

NASA Technical Reports Server (NTRS)

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.

Nicogossian, Arnauld E.

1992-01-01

343

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

NASA Technical Reports Server (NTRS)

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.

Levine, Joel S.

2011-01-01

344

Human Modeling for Ground Processing Human Factors Engineering Analysis  

NASA Technical Reports Server (NTRS)

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

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

345

Human Modeling For Ground Processing Human Factors Engineering Analysis  

NASA Technical Reports Server (NTRS)

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.

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

2011-01-01

346

Living Human Rights students raise awareness of ‘Human Trafficking’  

Microsoft Academic Search

Students from the unit Living Human Rights, from The University of Notre Dame Australia’s Fremantle Campus, recently held an expo to raise awareness of human trafficking.\\u000aThe unit, Living Human Rights, introduces students to human rights from a number of interrelated perspectives: global and local; professional and personal; present and historical. It explores how human rights need to form an

Cassidy Rebecca

2009-01-01

347

The Human Serum Metabolome  

PubMed Central

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

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

348

[Human ehrlichiosis. Review].  

PubMed

Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia canis has been known as a cause of illness in dogs and other canine species, and for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 98.7% related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been reported in USA. PCR amplification and sequence of 16S rDNA, showed that the human isolate was virtually identical to those reported for E. phagocytophila y E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is present. Some of them have complications such as pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia and elevated liver enzyme values have been common findings. Tetracycline and cloramphenicol have been using in adults and children as especific theraphy. PMID:7734523

Arraga-Alvarado, C

1994-12-01

349

Human herpesvirus 6.  

PubMed Central

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

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

1997-01-01

350

Human Skin Fungal Diversity  

PubMed Central

Traditional culture-based methods have incompletely defined the etiology of common recalcitrant human fungal skin diseases including athlete’s foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms, while providing a home for diverse commensal microbiota1. Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders2,3,4. However, microbial diversity is not limited to bacteria; microorganisms such as fungi also play major roles in microbial community stability, human health and disease5. Genomic methodologies to identify fungal species and communities have been limited compared with tools available for bacteria6. Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes7. Here, we sequenced and analyzed fungal communities of 14 skin sites in 10 healthy adults. Eleven core body and arm sites were dominated by Malassezia fungi, with species-level classifications revealing greater topographical resolution between sites. By contrast, three foot sites, plantar heel, toenail, and toeweb, exhibited tremendous fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that skin physiologic attributes and topography differentially shape these two microbial communities. These results provide a framework for future investigation of interactions between pathogenic and commensal fungal and bacterial communities in maintaining human health and contributing to disease pathogenesis. PMID:23698366

Findley, Keisha; Oh, Julia; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A.; Schoenfeld, Deborah; Nomicos, Effie; Park, Morgan; Kong, Heidi H.; Segre, Julia A.

2013-01-01

351

The Human Genome Program  

SciTech Connect

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.

Bell, G.I.

1989-01-01

352

Humanities Division UNIVERSITY OF OXFORD  

E-print Network

Humanities Division UNIVERSITY OF OXFORD HUMANITIES DIVISION MELLON POSTDOCTORAL FELLOWSHIP SCHEME A two-year research and teaching appointment in Digital Humanities from October 2011 for an outstanding Postdoctoral Fellow in Digital Humanities will: · take up appointment between 1 October 2011 and 1 January 2012

Oxford, University of

353

Human Challenges in Exploration Missions  

NASA Technical Reports Server (NTRS)

This viewgraph presents an overview using pictures some of the history of human exploration of the new frontiers of Earth and then examines some of the challenges to human exploration of space. Particular attention is given to the environmental factors and to the social and human factors that effect humans in space environments.

Lloyd, Charles W.

2007-01-01

354

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 ...

355

Humanities Division Janel Mueller, Dean  

E-print Network

Humanities Division Janel Mueller, Dean Thomas Thuerer, Dean of Students Larry Norman, Associate Dean Division of the Humanities 1010 East 59th Street University of Chicago Chicago, IL 60637 Tel: (773) 702-8512 Fax: (773) 702-9861 http://humanities.uchicago.edu Apply to Humanities Programs online

He, Chuan

356

Making IBM's Computer, Watson, Human  

ERIC Educational Resources Information Center

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…

Rachlin, Howard

2012-01-01

357

The Humanities at Triton College.  

ERIC Educational Resources Information Center

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

Jacot, Robert E.; Prendergast, Nancy E.

358

Human dignity and human tissue: a meaningful ethical relationship?  

PubMed

Human dignity has long been used as a foundational principle in policy documents and ethical guidelines intended to govern various forms of biomedical research. Despite the vast amount of literature concerning human dignity and embryonic tissues, the majority of biomedical research uses non-embryonic human tissue. Therefore, this contribution addresses a notable lacuna in the literature: the relationship, if any, between human dignity and human tissue. This paper first elaborates a multidimensional understanding of human dignity that overcomes many of the shortcomings associated with the use of human dignity in other ethical debates. Second, it discusses the relationship between such an understanding of human dignity and 'non-embryonic' human tissue. Finally, it considers the implications of this relationship for biomedical research and practice involving human tissue. The contribution demonstrates that while human tissue cannot be said to have human dignity, human dignity is nevertheless implicated by human tissue, making what is done with human tissue and how it is done worthy of moral consideration. PMID:21478417

Kirchhoffer, David G; Dierickx, Kris

2011-09-01

359

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.

360

Human Embryology Animations  

NSDL National Science Digital Library

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.

O'Loughlin, Valerie

2012-03-02

361

[Humanized antibodies as therapeutics].  

PubMed

Since 1997, nine humanized antibodies received the approval of the FDA to be used as drugs for the treatment of various diseases including transplant rejections, metastatic breast and colon cancers, leukaemia, non-Hodgkin lymphomas, allergic conditions or multiple sclerosis. This review describes techniques used to engineer these antibodies and presents the recent evolutions of these techniques : SDRs grafting or < abbreviated > CDRs grafting. Based on the illustrative examples of several antibodies, Mylotarg, Herceptin or Xolair, the therapeutic effectiveness of humanized antibodies are underlined and, with the example of Tysabri, the sometimes dramatic adverse effects associated with their clinical use is stressed. In a second part, this review presents some future and realistic avenues to improve the effectiveness of the humanized antibodies, to decrease their immunogenicity and to reduce their cost. PMID:16324646

Bellet, Dominique; Dangles-Marie, Virginie

2005-12-01

362

[Human rights and procreation].  

PubMed

The impact of procreation on freedom, health and welfare of human beings, is considerable. This relationship, however, is not mirrored in texts devoted to Human Rights. This omission obviously implies a neglect of women's and children's rights. The history of anticonceptive methods exemplifies the struggle for these rights. This conquest, which has lasted two hundred years, is far from completed. Because of the demographic outbreak in Third World countries, an ideological conflict has appeared between first generation Human Rights concerned with individual freedom ("rights of") and those of second generation aiming at social fairness ("rights to"). Adequate political and economic adjustment between North and South is a prerequisite to any balanced compromise that would resolve this conflict through democratic, albeit intensive, birth control. PMID:2339216

Leroy, F

1990-04-01

363

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.

364

Seaweed and human health.  

PubMed

Seaweeds may have an important role in modulating chronic disease. Rich in unique bioactive compounds not present in terrestrial food sources, including different proteins (lectins, phycobiliproteins, peptides, and amino acids), polyphenols, and polysaccharides, seaweeds are a novel source of compounds with potential to be exploited in human health applications. Purported benefits include antiviral, anticancer, and anticoagulant properties as well as the ability to modulate gut health and risk factors for obesity and diabetes. Though the majority of studies have been performed in cell and animal models, there is evidence of the beneficial effect of seaweed and seaweed components on markers of human health and disease status. This review is the first to critically evaluate these human studies, aiming to draw attention to gaps in current knowledge, which will aid the planning and implementation of future studies. PMID:24697280

Brown, Emma S; Allsopp, Philip J; Magee, Pamela J; Gill, Chris I R; Nitecki, Sonja; Strain, Conall R; McSorley, Emeir M

2014-03-01

365

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 âÂÂLinks, ideas, and tools for humanities instructors.â And thatâÂÂs exactly what it is. Curated by a history professor at Arizona State University (web name: Stillwater Humanities), the site âÂÂscoopsâ resources from around the web. Recent gems include articles like âÂÂHistoryâÂÂs Futureâ and âÂÂA Brief History of the Hashtag, and Other Unusual Punctuation Marks,â as well as infographics (for example, âÂÂ6 Ways Social Media Will Change in 2014âÂÂ) and blog entries (e.g. âÂÂWhat Digitization Will Do for the Future of MuseumsâÂÂ).

366

Human Ageing Genomic Resources  

NSDL National Science Digital Library

The Human Ageing Genomic Resources (HAGR)âÂÂcurrently led by Dr. João Pedro de Magalhães at the Harvard Medical SchoolâÂÂis "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, âÂÂa curated database of genes related to human ageing.â Site visitors are encouraged to download the HAGR software, Ageing Resources Computational Tools, which âÂÂis 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.

367

Preparing for Human Exploration  

NASA Technical Reports Server (NTRS)

NASA's Human Exploration and Development of Space (HEDS) Enterprise is defining architectures and requirements for human exploration that radically reduce the costs of such missions through the use of advanced technologies, commercial partnerships and innovative systems strategies. In addition, the HEDS Enterprise is collaborating with the Space Science Enterprise to acquire needed early knowledge about Mars and to demonstrate critical technologies via robotic missions. This paper provides an overview of the technological challenges facing NASA as it prepares for human exploration. Emphasis is placed on identifying the key technologies including those which will provide the most return in terms of reducing total mission cost and/or reducing potential risk to the mission crew. Top-level requirements are provided for those critical enabling technology options currently under consideration.

Drake, Bret G.; Joosten, B. Kent

1998-01-01

368

Teleoperator Human Factors Study  

NASA Technical Reports Server (NTRS)

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.

1986-01-01

369

Human tail and myelomeningocele.  

PubMed

The human tail is rarely reported and is usually associated with underlying spina bifida occulta. A male newborn presenting a caudal appendage (human tail) with skin-covered myelomeningocele and tethered cord is described. Surgical excision of the human tail and repair of the myelomeningocele were performed 3 days after birth. After the operation, the patient had an uneventful convalescence and received follow-up at our outpatient clinic without any neurological sequelae. To our knowledge, no similar case report exists in the literature. Like other skin-related lesions in the lumbosacral area, the present case of caudal appendage with myelomeningocele is only a cutaneous sign of underlying spinal dysraphism since the skin and nerve system are related by their similar ectodermal origin. After excision of the tail and repair of an underlying lesion, long-term follow-up of the neurological status is warranted. PMID:17627154

Lin, Pei-Jung; Chang, Yu-Tang; Tseng, Hsing-I; Lin, Jan-You; Huang, Yu-Sheng

2007-01-01

370

[Diagnosis of human toxocarosis].  

PubMed

Human toxocarosis is an important parasitic zoonosis caused by larval stages of Toxocara species, the roundworms from dogs and cats. Larval migration through different soft tissues in the human generates several clinical entities in the patient, such as visceral larva migrans, ocular toxocarosis, and neurotoxocarosis. Definitive diagnosis by histopathological methods is very difficult or almost impossible and, nowadays, the diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of hematological and immunological tests which finally help to confirm the clinical suspicion of the illness. The purpose of this paper was to update the available knowledge on the use of different tools for both the diagnosis and following up of human toxocarosis. PMID:21308204

Roldán, William H; Espinoza, Yrma A; Huapaya, Pedro E; Jiménez, Susana

2010-01-01

371

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"

372

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.

373

Mapping Human Epigenomes  

PubMed Central

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

Rivera, Chloe M.; Ren, Bing

2013-01-01

374

Human exploration mission studies  

NASA Technical Reports Server (NTRS)

The nation's efforts to expand human presence and activity beyond Earth orbit into the solar system was given renewed emphasis in January of 1988 when the Presidential Directive on National Space Policy was signed into effect. The expansion of human presence into the solar system has particular significance, in that it defines long-range goals for NASA's future missions. To embark and achieve such ambitious ventures is a significant undertaking, particularly compared to past space activities. Missions to Mars, the Moon, and Phobos, as well as an observatory based on the dark side of the Moon are discussed.

Cataldo, Robert L.

1989-01-01

375

Disorders of Human Hemoglobin  

NASA Astrophysics Data System (ADS)

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.

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

1980-02-01

376

Sanitation and Human Health  

NSDL National Science Digital Library

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.

Science Netlinks;

2000-12-06

377

Human MSH2 protein  

DOEpatents

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.

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

1997-01-01

378

Human MSH2 protein  

DOEpatents

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.

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

1997-01-07

379

Microsporidia and human infections.  

PubMed Central

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

Shadduck, J A; Greeley, E

1989-01-01

380

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.

381

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.

382

Human Development Index Data  

NSDL National Science Digital Library

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.

Nations, United

383

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.

384

Cardiovascular Deconditioning in Humans: Human Studies Core  

NASA Technical Reports Server (NTRS)

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.

Williams, Gordon

1999-01-01

385

Similarities and differences between human–human and human–automation trust: an integrative review  

Microsoft Academic Search

The trust placed in diagnostic aids by the human operator is a critical psychological factor that influences operator reliance on automation. Studies examining the nature of human interaction with automation have revealed that users have a propensity to apply norms of human–human inter-personal interaction to their interaction with ‘intelligent machines’. Nevertheless, there exist subtle differences in the manner in which

P. Madhavan; D. A. Wiegmann

2007-01-01

386

Have we overestimated the benefit of human(ized) antibodies?  

PubMed Central

The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account. PMID:20935511

Getts, Meghann T; McCarthy, Derrick P; Chastain, Emily ML; Miller, Stephen D

2010-01-01

387

Augmented Human Engineering: A Theoretical and Experimental  

E-print Network

. 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

Paris-Sud XI, Université de

388

Economics for Humans  

Microsoft Academic Search

Is it asking too much to demand that businesses be socially and environmentally responsible? When child care and elder care are commercially supplied, is caring turned into just another commodity? Many, believing that economies are cold and heartless systems that operate outside human control, would answer yes. But in this impassioned and perceptive work, Julie A. Nelson debunks theories that

Julie A. Nelson

2006-01-01

389

Extrapolating human probability judgment  

Microsoft Academic Search

We advance a model of human probability judgment and apply it to the design of an extrapolation algorithm. Such an algorithm examines a person's judgment about the likelihood of various statements and is then able to predict the same person's judgments about new statements. The algorithm is tested against judgments produced by thirty undergraduates asked to assign probabilities to statements

Daniel Osherson; Edward E. Smith; Tracy S. Myers; Eldar Shafir; Michael Stob

1994-01-01

390

Assemble the Human Heart  

NSDL National Science Digital Library

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.

Cosi

2000-01-01

391

Immunogenetics Human immunogenetics  

E-print Network

in the control of immune function and autoimmune diseases. Charles E Larsen The CBR Institute for Biomedical is the cellular immunology and genetics of the human nonresponse to hepatitis B vaccine. This interest has broadened to include the relationship between MHC genetic structure and autoimmune phenomena. Abbreviations

Alper, Chester A.

392

The Human Speechome Project  

Microsoft Academic Search

The Human Speechome Project is an e! ort to observe and computationally model the longitudinal course of language development for a single child at an unprece- dented scale. The idea is this: Instrument a child's home so that nearly everything the child hears and sees from birth to three is recorded. Develop a computa- tional model of language learning that

Deb Roy; Rupal Patel; Philip Decamp; Rony Kubat; Michael Fleischman; Brandon Roy; Nikolaos Mavridis; Stefanie Tellex; Alexia Salata; Jethran Guinness; Michael Levit; Peter Gorniak

2006-01-01

393

Animating human athletics  

Microsoft Academic Search

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

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

1995-01-01

394

Humanized Youth Work  

ERIC Educational Resources Information Center

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…

Brokenleg, Martin

2012-01-01

395

Human Aggression and Suicide  

ERIC Educational Resources Information Center

The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

Brown, Gerald L.; Goodwin, Frederick K

1986-01-01

396

Human Social Genomics  

PubMed Central

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

Cole, Steven W.

2014-01-01

397

The Human Potential Movement.  

ERIC Educational Resources Information Center

The advent of the human potential movement has generated the expectation that educators unleash the intellectual, emotional, physical, and spiritual talents of students. This movement is characterized by its focus on (1) the person as a total being, (2) the needs and concerns of students, (3) phenomenology, (4) personal values and goals, and (5)…

Tamashiro, Roy T.

398

Human Vaccines & Immunotherapeutics  

PubMed Central

DNA vaccine for T1D promising in the clinic HPV vaccines halved infections in US teenage girls Modified DC immunotherapy against melanoma New study looks at clinical severity of human H7N9 infections Prevnar vaccines are valuable for healthcare systems GAPVAC: New consortium in the fight of brain cancer Cytomegalovirus vaccine to enter phase 3 Malaria vaccination using chemically attenuated parasites

Riedmann, Eva M

2013-01-01

399

What Predicts Human Trafficking?  

Microsoft Academic Search

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,

Kevin Bales

2007-01-01

400

Fighting for the Humanities  

ERIC Educational Resources Information Center

The question, "Who will bankroll poetry?", succinctly embodies what is now a widespread recognition that the humanities may have more to lose in the current budget wars than either the sciences or a number of technical fields. The only budget war that can unite individuals, rather than divide them, is one arguing that too much is being spent on…

Nelson, Cary

2012-01-01

401

Solving the human predicament  

Microsoft Academic Search

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,

Paul R. Ehrlich; Anne H. Ehrlich

2012-01-01

402

RVF Appraising Human Vulnerability  

E-print Network

Foodborne Disease: Medical Costs and Productivity Losses. · These estimates were developed to provide 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;

McCarl, Bruce A.

403

Human social genomics.  

PubMed

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

Cole, Steven W

2014-08-01

404

Human Biology: Experimental.  

ERIC Educational Resources Information Center

Education is a process of adapting to change, and the rate of change is especially rapid in science today. This curriculum in human biology is an alternative to the New York State courses in general and Regents biology, and it has been designed to focus on change from the standpoint of the urban student. It is designed to provide students with…

New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

405

Humanizing the Workplace.  

ERIC Educational Resources Information Center

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…

Fairfield, Roy P., Ed.

406

Mapping the Human Record  

Microsoft Academic Search

This chapter examines the changing human demography of Britain during the Lower and early Middle Palaeolithic using Palaeolithic handaxe densities in the Middle Thames and Solent rivers as proxies for relative population. Peak populations are suggested for Marine Isotope Stages (MISs) 13 and 11, and population decline is indicated after MIS 10. This data is compared to the individual site

Nick Ashton; Simon G. Lewis; Robert Hosfield

2011-01-01

407

Genetic Modifications in Humans  

Microsoft Academic Search

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

Erin McHale

408

Human and information  

NASA Astrophysics Data System (ADS)

This is a lecture at the 15th anniversary of JICST Chugoku Branch Office. A recent progress of VLSI technologies will make possible to simulate some functions of human beings, the results of which will prepare next new innovation for a coming now century.

Mizuno, Hiroyuki

409

Rabies Diagnosis in Human  

Microsoft Academic Search

Rabies diagnosis in humans can be made by obtaining a history of exposure particularly to an animal bite, clinical symptoms and signs, neuroimaging such as magnetic resonance imaging (MRI) and laboratory testing. Although diagnosis made by clinical grounds alone can be useful, this can only be limited to furious rabies. Owing to the fact that there is more than one

Supaporn Wacharapluesadee

410

Human performance measuring device  

NASA Technical Reports Server (NTRS)

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.

Michael, J.; Scow, J.

1970-01-01

411

Biotechnologies and Human Dignity  

ERIC Educational Resources Information Center

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…

Sweet, William; Masciulli, Joseph

2011-01-01

412

Synthesizing Humanism and Behaviorism.  

ERIC Educational Resources Information Center

The old argument of humanism versus behaviorism is slowly being replaced by a synthesis of these two foundations of thought. This slow professional recognition of synthesis is due to three basic shortcomings in the professional community rather than extreme differences in ideological thought. They are: (1) psychological terminology being equated…

Linder, Steven

413

The Humanization of Science.  

ERIC Educational Resources Information Center

Describes an exercise which focuses on the ethical and human aspects of science. Outlines the approach and components of a writing assignment based on a literary and humanistic analysis of "The Double Helix" by James Watson. Provides sample questions and examples of integrative literary works. (ML)

Larson, James H.

1986-01-01

414

Lessons in Human Relations.  

ERIC Educational Resources Information Center

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)

Glenn, Joanne Lozar

2003-01-01

415

The Humanities, Unraveled  

ERIC Educational Resources Information Center

Graduate education in the humanities is in crisis. Every aspect, from the most specific details of the curriculum to the broadest questions about its purpose, is in crisis. It is a seamless garment of crisis: If one pulls on any one thread, the entire thing unravels. It is therefore exceptionally difficult to discuss any one aspect of graduate…

Berube, Michael

2013-01-01

416

"Healthy" Human Development Indices  

ERIC Educational Resources Information Center

In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

Engineer, Merwan; Roy, Nilanjana; Fink, Sari

2010-01-01

417

HHMI Human Embryonic Development  

NSDL National Science Digital Library

This video provides a talk and video illustration of the anatomical changes during human embryonic development. A clever feature of the video is that it compares the size of the growing fetus to a known shape to be able to draw comparisons. This is presented by HHMI's Biointeractive Series.

HHMI (Howard Hughes Medical Institute)

2006-12-01

418

Predictors of human rotation.  

PubMed

Why some humans prefer to rotate clockwise rather than anticlockwise is not well understood. This study aims to identify the predictors of the preferred rotation direction in humans. The variables hypothesised to influence rotation preference include handedness, footedness, sex, brain hemisphere lateralisation, and the Coriolis effect (which results from geospatial location on the Earth). An online questionnaire allowed us to analyse data from 1526 respondents in 97 countries. Factor analysis showed that the direction of rotation should be studied separately for local and global movements. Handedness, footedness, and the item hypothesised to measure brain hemisphere lateralisation are predictors of rotation direction for both global and local movements. Sex is a predictor of the direction of global rotation movements but not local ones, and both sexes tend to rotate clockwise. Geospatial location does not predict the preferred direction of rotation. Our study confirms previous findings concerning the influence of handedness, footedness, and sex on human rotation; our study also provides new insight into the underlying structure of human rotation movements and excludes the Coriolis effect as a predictor of rotation. PMID:22708777

Stochl, Jan; Croudace, Tim

2013-05-01

419

Biomedical Ethics & Medical Humanities  

E-print Network

students to reflect on, analyze and contribute to the meaning of medicine by focusing on one (or more, philosophy, history, religion, and the arts (visual, theatre, media), as well as humanities-oriented social of medicine; issues of health care access and public health policy; doctor-patient relationship

Ford, James

420

Potatoes and Human Health  

Microsoft Academic Search

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

Mary Ellen Camire; Stan Kubow; Danielle J. Donnelly

2009-01-01

421

Humane Treatment of Animals.  

ERIC Educational Resources Information Center

This booklet is designed to give teachers resource information about the humane treatment of and care for animals. The topics are presented as springboards for discussion and class activity. Topics include the care of dogs, cats, birds, horses, and fish; wildlife and ecological relationships; and careers with animals. Illustrations on some pages…

Dawson, Joan Smithey

422

Human Memory: The Basics  

ERIC Educational Resources Information Center

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.

Martinez, Michael E.

2010-01-01

423

Human Resource Management Concentration  

E-print Network

Historical Perspectives (3D) Students MUST complete CO150 and MATH141 by the time they complete 60 credits........................................................................................fall MGT474............Human Resource Planning and Development .......MGT310........................................................................................fall, spring Internship Coordinator Bill Shuster � 215 Rockwell Hall � (970) 491-4023 � bill

Barnes, Elizabeth A.

424

Rise of human intelligence  

Microsoft Academic Search

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

Fernand Gobet; Guillermo Campitelli; Andrew J Waters

2002-01-01

425

Glasgow Human Rights Network  

E-print Network

, gay, bisexual and transgender pride festival celebrating the diversity of the LGBT community (lecture theatre) Chair: Becky Kent Scottish Transgender Alliance Bisi Alimi LGBT/HIV advocate and lecturer, Free University of Berlin (Nigeria) Monica Tabengwa LGBT Rights Programme, Human Rights Watch (Botswana

Guo, Zaoyang

426

The Human Connection  

ERIC Educational Resources Information Center

Without effective classroom management, teaching and learning cannot take place. The responsibility for a teacher's success in the classroom lies as much in the human connection between administrator and teacher as between teacher and student. In fact, it lies with all who work with schools: universities, school boards, administrators, and…

Holliday, Christina O.

2005-01-01

427

Food Affects Human Behavior.  

ERIC Educational Resources Information Center

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)

Kolata, Gina

1982-01-01

428

Neurobiology and the humanities.  

PubMed

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

Zeki, Semir

2014-10-01

429

Doctors and human rights  

Microsoft Academic Search

This article describes the roles of Amnesty International's Medical Groups and the Medical Foundation for the Care of Victims of Torture in campaigning for and treating those suffering the physical and psychological effects of human rights abuse in peace and war.

Duncan M. Forrest

1991-01-01

430

Human Islet Transplantation: Update  

Microsoft Academic Search

New hope for the treatment of type 1 diabetes has recently emerged from the encouraging results of islet cell transplantation in humans during the last few years. Although still facing considerable problems, the challenge to achieving insulin independence has been overcome in some patients who received an islet graft. However, the success of clinical trials is still limited by the

Andres Boker; Lisa Rothenberg; Claudia Hernandez; Norma S. Kenyon; Camillo Ricordi; Rodolfo Alejandro

2001-01-01

431

Recombinant Human Milk Proteins  

Microsoft Academic Search

Human milk provides proteins that benefit newborn infants. They not only provide amino acids, but also facilitate the absorption of nutrients, stimulate growth and development of the intestine, modulate immune function, and aid in the digestion of other nutrients. Breastfed infants have a lower prevalence of infections than formulafed infants. Since many women in industrialized countries choose not to breastfeed,

2006-01-01

432

Animal and Human Communication.  

ERIC Educational Resources Information Center

Several misconceptions regarding the status of human communication systems relative to the systems of other animals are discussed in this paper. Arguments are offered supporting the expansion of the communication discipline to include the study of the communication systems of other species. The "communicative continuity" view which ranks man at…

Rummel, Lynda

433

Occupying the Digital Humanities  

ERIC Educational Resources Information Center

This essay questions the digital humanities' dependence on interpretation and critique as strategies for reading and responding to texts. Instead, the essay proposes suggestion as a digital rhetorical practice, one that does not replace hermeneutics, but instead offers alternative ways to respond to texts. The essay uses the Occupy movement as an…

Rice, Jeff

2013-01-01

434

On Cloning Human Beings  

Microsoft Academic Search

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

Inmaculada de Melo-Martín

2002-01-01

435

Hydroxytyrosol Disposition in Humans  

Microsoft Academic Search

Background: Animal and in vitro studies suggest that phenolic compounds in virgin olive oil are effective antioxidants. In animal and in vitro studies, hydroxyty- rosol and its metabolites have been shown to be strong antioxidants. One of the prerequisites to assess their in vivo physiologic significance is to determine their pres- ence in human plasma. Methods: We developed an analytical

Elisabet Miro-Casas; Maria-Isabel Covas; Magi Farre; Montserrat Fito; Jordi Ortuno; Tanja Weinbrenner; Pere Roset; Rafael de la Torre

436

Human Exploration of Mars  

Microsoft Academic Search

Novel approaches to the human exploration of Mars are considered with emphasis on a space suit design, extraterrestrial surface mobility, and water supply. A possible way of transporting personnel on the surface of Mars uses a suborbital rocket that will hop from one site to the next, refuelling each time it lands and giving the Martian explorers effective global mobility.

Owen Gwynne; Chris McKay; Robert Zubrin

1991-01-01

437

Communicating with Virtual Humans.  

ERIC Educational Resources Information Center

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…

Thalmann, Nadia Magnenat

438

HUMAN GENETICS Individualgenomesdiversify  

E-print Network

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

Zhang, Xin

439

Learning to Be Human  

ERIC Educational Resources Information Center

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…

Macmurray, John

2012-01-01

440

Testosterone in human saliva  

Microsoft Academic Search

Summary Testosterone has been detected in whole human saliva. Levels averaged (±SE) 295±36 and 195±25 pg\\/ml in adult males and females, respectively, and usually were undetectable in children. In adult males, the excretion of testosterone in saliva appeared to follow a circadian rhythm.

A. D. Landman; L. M. Sanford; B. E. Howland; C. Dawes; E. T. Pritchard

1976-01-01

441

Human-Robot Interaction  

NASA Technical Reports Server (NTRS)

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.

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

2015-01-01

442

Human genome analysis and the concept of human nature.  

PubMed

The possibilities opened up by human genome analysis appear to provide support for quasi-deterministic views of human nature but an analysis of the debate over sociobiology shows that we cannot derive a theory of human nature directly from biological and genetic evidence. From this perspective human genome analysis and the forms of human genetic engineering that it makes possible cannot alter our concept of human nature although they make us more aware of the 'plasticity' of the human. The possibility envisaged by some neo-eugenicists (and often accepted by their opponents) of a radical reshaping of human nature is as misconceived as the view of some sociobiologists that human nature is biologically determined. Human genome analysis raises formidable ethical, social and legal problems and we need to develop criteria that will enable us to decide which kinds of genetic manipulation will help to enhance human life and which will not. This will involve having a clear concept of human nature and the values it implies. But we shall not derive this concept of human nature from genetics itself. PMID:2335122

Charlesworth, M

1990-01-01

443

Modelling of human herpesvirus infections in humanized mice.  

PubMed

The human herpesviruses (HHVs) are remarkably successful human pathogens, with some members of the family successfully establishing infection in the vast majority of humans worldwide. Although many HHV infections result in asymptomatic infection or mild disease, there are rare cases of severe disease and death found with nearly every HHV. Many of the pathogenic mechanisms of these viruses are poorly understood, and in many cases, effective antiviral drugs are lacking. Only a single vaccine exists for the HHVs and researchers have been unable to develop treatments to cure the persistent infections associated with HHVs. A major hindrance to HHV research has been the lack of suitable animal models, with the notable exception of the herpes simplex viruses. One promising area for HHV research is the use of humanized mouse models, in which human cells or tissues are transplanted into immunodeficient mice. Current humanized mouse models mostly transplant human haematopoietic stem cells (HSCs), resulting in the production of a variety of human immune cells. Although all HHVs are thought to infect human immune cells, the beta- and gammaherpesviruses extensively infect and establish latency in these cells. Thus, mice humanized with HSCs hold great promise to study these herpesviruses. In this review, we provide a historical perspective on the use of both older and newer humanized mouse models to study HHV infections. The focus is on current developments in using humanized mice to study mechanisms of HHV-induced pathogenesis, human immune responses to HHVs and effectiveness of antiviral drugs. PMID:25053560

Berges, Bradford K; Tanner, Anne

2014-10-01

444

Human Capital Accumulation: The Role of Human Resource Development.  

ERIC Educational Resources Information Center

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)

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

2001-01-01

445

Adsorption of Human Papillomavirus 16 to live human sperm  

E-print Network

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 ...

Ribbeck, Katharina

446

Generating human-like soccer primitives from human data  

Microsoft Academic Search

Recently, interest in analysis and generation of human and human-like motion has increased in various areas. In robotics, in order to operate a humanoid robot, it is necessary to generate motions that have strictly dynamic consistency. Furthermore, human-like motion for robots will bring advantages such as energy optimization.This paper presents a mechanism to generate two human-like motions, walking and kicking,

Carlos Antonio Acosta Calderon; Rajesh Elara Mohan; Lingyun Hu; Changjiu Zhou; Huosheng Hu

2009-01-01

447

Effect of Human Angiostatin ® Protein on Human Angiogenesis in vitro  

Microsoft Academic Search

Angiostatin®, a 38-kD fragment of plasminogen, inhibits angiogenesis in both animal tumor models and in vitro endothelial cell models. However, human Angiostatin® has not been tested in vitro against an intact human tissue target to determine its ability to inhibit the initiation or subsequent promotion of the human\\u000a angiogenic response. We hypothesized that high doses of human Angiostatin® would inhibit

Sung Pil Jung; Brett Siegrist; Yi-Zarn Wang; Mark R. Wade; Catherine T. Anthony; Conrad Hornick; Eugene A. Woltering

2003-01-01

448

Department of Humanities Program in Technology and the Humanities  

E-print Network

; ethics in the professions; history of art and architecture; humanizing technology; information seek- ing of Humanities Writing Center, and Associate Director for ESL Programs. B.A., M.S., Indiana University. Davis, Associate Chair, Director for ESL Programs, and Undergraduate Advisor in the Department of Humanities . B

Heller, Barbara

449

The Human Connectome: A Structural Description of the Human Brain  

Microsoft Academic Search

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

Olaf Sporns; Giulio Tononi; Rolf Kötter

2005-01-01

450

Human evolution: Origins of modern humans still look recent  

Microsoft Academic Search

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.

Todd R. Disotell

1999-01-01

451

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

452

Visible Human Server  

NSDL National Science Digital Library

This Web site from the Swiss Federal Institute of Technology allows users to view three dimensional models of human anatomy. A free registration allows users to log on and fully access the site, but there are some sample demonstrations available without registration. When visiting the site, you can view, rotate, and extract cross sections from the anatomical models, or build your own anatomic model by choosing the structures of interest. The site works best with Internet Explorer 5 and the latest version of Microsoft Java VM. The site provides how-to files that are extremely helpful for new users. This is certainly a site for those studying human anatomy, but it is a cool site that may also appeal to others. This site is also reviewed in the April 5, 2002 NSDL Life Sciences Report.

1998-01-01

453

Humbul Humanities Hub  

NSDL National Science Digital Library

Funded by the Joint Information Systems Committee and hosted by the University of Oxford, the Humbul Humanities Hub is a service of the Resource Discovery Network. The site is geared towards meeting the needs of the humanities community and includes information in areas ranging from language and literature, to American studies, to archaeology, to philosophy. Furthermore, this site contains a searchable archive with links to various museums and libraries. During its nascent stage, this site was covered in the Scout Report's July 22, 1994 edition. However, since then, the site has added geography, education, sport, and tourism/leisure in order to ensure that interdisciplinary subjects are adequately covered. These additions give its visitors greater flexibility and diversity in deciding what to search for and how to conduct a search.

2001-01-01

454

Illinois Humanities Council  

NSDL National Science Digital Library

Based in Chicago, the Illinois Humanities Council (IHC) is "an educational organization dedicated to fostering a culture in which the humanities are a vital part of the lives of individuals and communities." Their work emphasizes the analysis, interpretation, and exchange of ideas through grant-making activities, lecture series, and community events work to enhance the lives of Illinois residents. On their website, visitors can read through their Who We Are section to learn more about their work and also check out the Watch, Listen, and Learn area to view past presentations and events. Some of the series featured here cover Conversations on Oil and Water and profiles of Illinois writers and artists. Visitors interested in applying for a grant from the IHC should click on the Grants area to learn about their guidelines and the application process.

455

Human Development Report 2006  

NSDL National Science Digital Library

Every year, many policy specialists and government officials eagerly await the annual Human Development Report issued by the United Nations Development Programme. Released in early November 2006, this year�s report was primarily focused on the issue of water, and they remarked, �unclean water is an immeasurably greater threat to human security that violent conflict.� Within its 440 page, the report investigates the underlying causes and consequences of this crisis, along with arguing for �a concerted drive to achieve water and sanitation for all through national strategies and a global plan of action.� Along with significant appendices, the report also contains special contributions from President Jimmy Carter, Gordon Brown, and UN Secretary General Kofi Annan.

2007-02-05

456

Human Development Report 2006  

NSDL National Science Digital Library

Every year, many policy specialists and government officials eagerly await the annual Human Development Report issued by the United Nations Development Programme. Released in early November 2006, this yearâÂÂs report was primarily focused on the issue of water, and they remarked that, âÂÂunclean water is an immeasurably greater threat to human security that violent conflict.â Within its 440 page, the report investigates the underlying causes and consequences of this crisis, along with arguing for âÂÂa concerted drive to achieve water and sanitation for all through national strategies and a global plan of action.â Along with significant appendices, the report also contains special contributions from President Jimmy Carter, Gordon Brown, and UN Secretary General Kofi Annan.

2006-01-01

457

How Did Humans Evolve?  

NSDL National Science Digital Library

In this lesson, students learn about the process of human evolution by interacting with a Web activity and examining possible hominid family trees. With this hands-on approach, students become responsible for their own learning and are better able to see connections between ideas and remember what they learn. In an activity called Fossil Finding, students will study four famous fossil groups and learn how scientists interpret them to explain human evolution. Students will understand how fossil evidence can be used to describe ancient life forms, learn about different kinds of fossil evidence, and how paleontologists compare information from different fossil finds to learn more about ancient life forms. In the second activity students will study three possible hominid family trees and examine why they are different. Each activity has a list of objectives and links to detailed instruction. The lesson also offers links to an assessment rubric, the national science standards for the lesson, and additional activities.

458

Maine Humanities Council  

NSDL National Science Digital Library

Formed as a private nonprofit organization, the Maine Humanities Council (MHC) "promotes strong communities and informed citizens by providing Mainers with opportunities to explore the power and pleasure of ideas." Their work is supported by volunteer board members, and their projects include programs to promote reading and writing, guest lectures around the state, and online newsletters and discussion groups. In the "Programs" area, visitors can learn about these programs, and educators can check out the resources created especially for them. The "Connections" area contains links to their thoughtful blog, their "Humanities on Demand" podcasts, and their periodic newsletter "Synapse", which deals with medicine and literature. The podcasts are quite fun, and they include "Franco-American Women's Words in Maine" and a talk by Professor Dianne Sadoff of Rutgers University on Middlemarch, by George Eliot.

459

Human biology of taste.  

PubMed

Taste or gustation is one of the 5 traditional senses including hearing, sight, touch, and smell. The sense of taste has classically been limited to the 5 basic taste qualities: sweet, salty, sour, bitter, and umami or savory. Advances from the Human Genome Project and others have allowed the identification and determination of many of the genes and molecular mechanisms involved in taste biology. The ubiquitous G protein-coupled receptors (GPCRs) make up the sweet, umami, and bitter receptors. Although less clear in humans, transient receptor potential ion channels are thought to mediate salty and sour taste; however, other targets have been identified. Furthermore, taste receptors have been located throughout the body and appear to be involved in many regulatory processes. An emerging interplay is revealed between chemical sensing in the periphery, cortical processing, performance, and physiology and likely the pathophysiology of diseases such as diabetes. PMID:23793421

Gravina, Stephen A; Yep, Gregory L; Khan, Mehmood

2013-01-01

460

Human papillomavirus genome variants  

PubMed Central

Amongst the human papillomaviruses (HPVs), the genus Alphapapillomavirus contains HPV types that are uniquely pathogenic. They can be classified into species and types based on genetic distances between viral genomes. Current circulating infectious HPVs constitute a set of viral genomes that have evolved with the rapid expansion of the human population. Viral variants were initially identified through restriction enzyme polymorphisms and more recently through sequence determination of viral fragments. Using partial sequence information, the history of variants, and the association of HPV variants with disease will be discussed with the main focus on the recent utilization of full genome sequence information for variant analyses. The use of multiple sequence alignments of complete viral genomes and phylogenetic analyses have begun to define variant lineages and sublineages using empirically defined differences of 1.0–10.0% and 0.5–1.0%, respectively. These studies provide the basis to define the genetics of HPV pathogenesis. PMID:23998342

Burk, Robert D.; Harari, Ariana; Chen, Zigui

2014-01-01

461

Human BAC Ends  

PubMed Central

The Human BAC Ends database includes all non-redundant human BAC end sequences (BESs) generated by The Institute for Genomic Research (TIGR), the University of Washington (UW) and California Institute of Technology (CalTech). It incorporates the available BAC mapping data from different genome centers and the annotation results of each end sequence for the contents of repeats, ESTs and STS markers. For each BAC end the database integrates the sequence, the phred quality scores, the map and the annotation, and provides links to sites of the library information, the reports of GenBank, dbGSS and GDB, and other relevant data. The database is freely accessible via the web and supports sequence or clone searches and anonymous FTP. The relevant sites and resources are described at http://www. tigr.org/tdb/humgen/bac_end_search/bac_end_intro.html PMID:10592201

Zhao, Shaying

2000-01-01

462

Secure Distributed Human Computation  

NASA Astrophysics Data System (ADS)

In Peha’s Financial Cryptography 2004 invited talk, he described the Cyphermint PayCash system (see www.cyphermint.com), which allows people without bank accounts or credit cards (a sizeable segment of the U.S. population) to automatically and instantly cash checks, pay bills, or make Internet transactions through publicly-accessible kiosks. Since PayCash offers automated financial transactions and since the system uses (unprotected) kiosks, security is critical. The kiosk must decide whether a person cashing a check is really the person to whom the check was made out, so it takes a digital picture of the person cashing the check and transmits this picture electronically to a central office, where a human worker compares the kiosk’s picture to one that was taken when the person registered with Cyphermint. If both pictures are of the same person, then the human worker authorizes the transaction.

Gentry, Craig; Ramzan, Zulfikar; Stubblebine, Stuart

463

Human waves in stadiums  

NASA Astrophysics Data System (ADS)

Mexican wave first widely broadcasted during the 1986 World Cup held in Mexico, is a human wave moving along the stands of stadiums as one section of spectators stands up, arms lifting, then sits down as the next section does the same. Here we use variants of models originally developed for the description of excitable media to demonstrate that this collective human behaviour can be quantitatively interpreted by methods of statistical physics. Adequate modelling of reactions to triggering attempts provides a deeper insight into the mechanisms by which a crowd can be stimulated to execute a particular pattern of behaviour and represents a possible tool of control during events involving excited groups of people. Interactive simulations, video recordings and further images are available at the webpage dedicated to this work: http://angel.elte.hu/wave.

Farkas, I.; Helbing, D.; Vicsek, T.

2003-12-01

464

MIS - The Human Connection  

PubMed Central

The lessons of the 70's with MIS were largely painful, often the same as those of the 60's, and were found in different phases on two continents. On examination this turns out to be true for many non-medical fields, true for systems programming, and thus a very general phenomenon. It is related to the functional complexity rather than to the sheer size of the software required, and above all to the relative neglect of human factors at all levels of software and hardware design. Simple hierarchical theory is a useful tool for analyzing complex systems and restoring the necessary dominance of common sense human factors. An example shows the very large effects of neglecting these factors on costs and benefits of MIS and their sub-systems.

Bush, Ian E.

1980-01-01

465

Human Development Reports  

NSDL National Science Digital Library

âÂÂPeople are the real wealth of a nation.â So began the first United Nations Development ProgrammeâÂÂs Human Development Report almost a quarter century ago. Issued annually, subsequent reports have included such themes as Sustainability and Equity (2012) and Cultural Liberty in TodayâÂÂs World (2004). The 2014 report, Sustaining Human Progress: Reducing Vulnerabilities and Building Resilience, argues that, though the number of people living in poverty has decreased substantially in the last few decades, there is still much work to be done. In addition to the current report, which can be downloaded for free, readers may want to click on Access Media Package, which provides succinct press releases for the whole report, as well as reports by five distinct geographical regions. Interested parties may also access 24 years of previous reports.

466

Human herpesvirus 8.  

PubMed

Human herpesvirus 8 (HHV 8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a g2 herpesvirus and the most recently identified human tumor virus. HHV 8 has been consistently implicated in the pathogenesis of all clinical variants of Kaposi's sarcoma, as well as in the plasma cell variant of multicentric Castleman's disease and primary effusion lymphomas. Pathogenicity of the virus is increased in the host who is immunosuppressed, either iatrogenically or through H1V-1 infection. The HHV 8 genome contains several homologues of cellular genes that regulate cell growth and differentiation, and the exact mechanisms of the virus' oncogenicity using molecular piracy are still being investigated and elucidated. In this article, the authors review the epidemiology, transmission, clinical manifestations, and molecular genetics of HHV 8 infection and provide a summary of the current treatment modalities available to the clinician. PMID:12120444

Martinelli, Paul T; Tyring, Stephen K

2002-04-01

467

[Human dignity revisited].  

PubMed

Since World War II, human dignity has made its way into many constitutions, bills of rights and international treaties. As its roots can be traced easily back to the Judeo-Christian tradition, and, later on, to the influential Kantian vision, dignity cannot be deemed an entirely new concept. For the same token, it cannot be said that dignity has been entirely alien to the legal realm till 1945. On the other hand, the latest philosophical and anthropological trends, as well as the politicisation of the human being, along with some recent advances in biotechnologies, help to explain its growing presence in the legal world. However, these authors suggest that writing down dignity in legal texts does not fully settle its meaning, not even if such texts are constitutions, and the fact remains that its presence in the judicial reasoning does not always imply being the ratio decidendi, as the study of some relevant judicial decisions shows. PMID:25329413

Pereira-Menaut, Antonio Carlos; Pereira Sáez, Carolina

2014-01-01

468

Hyaluronan in human malignancies  

SciTech Connect

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.

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

469

Human Development Report  

NSDL National Science Digital Library

Released on Monday July 12, the tenth edition of the United Nation Development Programme's (UNDP) Human Development Report has garnered considerable attention from the international press all week. The report ranks 174 countries on quality of life indicators such as life expectancy, wealth, and literacy, ranking Canada at the top and Sierra Leone at the bottom. The report pays particular attention to the opportunities and dangers of globalization. Although living conditions in almost all countries have improved over the last ten years, according to the report, economic inequalities have reached "grotesque" proportions, "with the richest fifth of humanity enjoying more than 85% of total gross domestic product and the poorest fifth only 1%." Users can download the full text and statistical tables of the report by chapter at the UNDP site. Additional resources include an Online Newsroom, which contains a press kit, author information, early reviews, and a feature on the HDR team.

1999-01-01

470

Director Human Resources Assoc Director  

E-print Network

Director ­ Human Resources Assoc Director Workforce Planning & Organisational Change Director ­ Human Resources Employment Services Support staff - EA/Receptionist - Snr Admin (Finance strategy - Recruitment strategy - Senior Appointments - Classifications & senior salaries - Academic

Botea, Adi

471