bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 2,4-Diaminopteridines with Bulky Lipophilic Groups at the 6-Position as Inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mammalian Dihydrofolate Reductase
Authors: Rosowsky Andre , Forsch Ronald A. , Queener Sherry F. , Bertino Joseph R. 
Published: March 2013

SummaryTen previously undescribed 2,4-diamino-6-(2-naphthylamino )methylpteridines with lipophilic chlorine or long-chain alkyl groups on the naphthyl moiety and either hydrogen or a methyl group on N 10 were synthesized from the appropriate 2-naphthylamine or N-methyl-2-naphthylamine by reaction with 2-amino-5-chloromethylpyrazine-3-carbonitrile and ring closure with guanidine . One analogue with a methyl group at the 7 -position was also prepared. The N 10 -unsubstituted analogues were consistently less active than the N1o-methyl analogues as inhibitors of Pneumocystis carin ii, Toxoplasma gondii, and rat liver dihydrofolate reductase. However the potency of the series as a whole was relatively low against all three enzymes, with the best inhibitors giving ICoo values only in the 0.1-1.0 ~M range and several giving IC50 values in the 10-100 ~M range. Moreover, while several compounds with ICso values of <10 ~M showed some selectivity for the Pnellmocystis carinii and/or Toxoplasma gondii enzyme relative to the rat liver enzme, the magnitude of this effect was marginal «4-fold). Assays were also performed against purified human dihydrofolate reductase and against wild-type and methotrexateresistant human leukemic lymphoblasts in culture. Activity against the enzyme was very low, the best inhibitors giving only 50-70% inhibition at 10 ~M. Although none of the compounds inhibited the growth of wild-type CEM cells by more than 20% at 1 ~M, several were more active (60-75% inhibition at 1 ~M) against the methotrexate-resistant subline CEM/MTX, which is defective in methotrexate and reduced folate transport, than they were against the methotrexate-sensitive parental CEM cells. Overall the results suggest that 2,4-diamino-6-substituted pteridines with chlorine or long-chain alkyl substituents in the 2-naphthyl moiety and hydrogen or a methyl group on NIO are not likely to be therapeutically useful agents.
In vivo Stimulatory Effects of Neopterin on Hematopoiesis
Authors: Aizawa Shin , Hiramoto Masaki , Araki Sonoko , Hosh Hajime , Kojima Shuji , Wakasugi Kazunori 
Published: March 2013

Summary The pteridine neopterin (NP) was shown to be produced by monocytes and has been known as a useful maker of immunological activation, although, the biological activity of this agent is still unclear. To elucidate the biological function of NP, the changes in the number of blood leukocyte, bone marrow and spleen hemopoietic progenitor cells after intraperitoneal administration of NP into mice were investigated. Administration of NP increased the number of blood leukocytes about 2 fold higher than that of the control at days 7 and 14. Blood films, made by smearing samples of peripheral blood, showed the increment of granulocytes in blood of NP treated animals. The number of granulocyte-macrophage progenitor cells (CFU-GM) was also increased in both bone marrow and spleen in mice with NP administration. Extensive study showed that NP stimulated the hematological recovery in bone marrow transplanted animals. All these findings suggest that NP has a stimulating activity on hemopoiesis by affecting the proliferation and differentiation of hemopoietic progenitor cells in vivo.
Correlations of Serum and Urine Levels of Neopterin, IL-8, IL-6, IL-6R, Basic Fetoprotein and Hepatocytes Growth Factor with Acute Rejection in kidney Transplantation
Authors: Miki Tsuneharu , Takahara Shiro , Okuyma Akihiko 
Published: March 2013

Summary Levels of serum- and urinary-neopterin and serum-IL-6 and IL-6R of kidney transplant recipients "Were higher in acute rejection episode than in stable condition. IL-8 serum levels had risen prior to clinical diagnosis of acute rejection episode. Serum HGF levels also increased during acute rejection episode to over 1 ng/ml. Serum-neopterin and IL-6R levels were relatively sensitive for the detection of acute rejection episode.
Proton NMR Studies on the Conformation of the Pterin Cofactor Bound at the Active Site of Recombinant Human Tyrosine Hydroxylase
Authors: Martínez Aurora , Vageli Olga , Pfleiderer Wolfgang , Flatmark Torgeir 
Published: March 2013

SummaryThe binding of L-erythro-7,S-dihydrobiopterin (BH2) in the presence of L-Phe to recombinant human tyrosine hydroxylase was studied by 1H-NMR spectroscopy. The distances (± 1.3 A) from the active site metal were estimated to be 5 .3-6.4 A for observable protons of BH2 and 7 .0-7.9 A for L-Phe protons. Due to the lack of constraints from the pyrimidine ring in BH2 , two families of conformers were computed, with an average distance from the C4a in the pterin ring to the iron of 3.7 A (family A) and S.S A (family B). The conformers for 6-methyl-tetrahydropterin bound to the enzyme at near anaerobic conditions in the absence of L-Phe were also grouped into two families, with C4a-metal distances of 3.0-4.0 A (A) and 7.0-7.5 A (B). Based on the estimated conformation of the enzyme bound 5,6,7,S-tetrahydro- 3-methylpterin, family A of conformers was selected for both oxidized and reduced pterins. Our results indicate that the pterin does not coordinate to the iron, which seems to be involved both in the binding and activation of O2 and in the C-O bond formation in the aromatic ring of the substrate.
Biosynthetic Enzymes of Tetrahydrolimipterin from Green Sulfur Bacterium Chlorobium Limicola
Authors: Kang Dongmin , Kim Sangjoon , Yim Jeongbin 
Published: March 2013

Summay Based on the structure of limipterin (Cha, Pfleiderer, and Yim, Helv, Chim. Acta, 78: 600-614. 1995 the biosynthetic pathway for the newly identified pterin glycoside was investigated. It was demonstrated that tetrahydrolimipterin (H4 -limipterin) can be synthesized from GTP by the enzymes GTP cyclohydrolase I, 6-pyruvoyltetrahydropterin (PTP) synthase, sepiaptcrin reductase and limipterin synthase, present in the extract of Chlorobium limicola. Limipterin synthase (UDP-N -acetylglucosamine:5 ,6,7 ,8-tetrahydro-L-biopterin 2'-O-β-N-acetylglucosaminyl transferase) catalyzed the condensation of tetrahydrobiopterin (H4-biopterin) with UDP-N-acetylglucosamine in the presence of dithiothreitol and MnCl2. It could also produce D-tepidopterin, [1-O-(D-threo- biopterin-2'-yl)- β-N -acetylglucosamine] when 5,6,7 ,8-tetrahydro-D-threobiopterin and UDP-N-acetylglucosamine were used as substrates . Substrate analogues such as UTP, UDP and UDP-Nacetylgalactosamine inhibit the enzyme activity. The Km values for tetrahydrobiopterin and UDP-N-acetylglucosamine were 42.2 μM and 124.3 μM, respectively. Optimum pH and temperature were pH 8.0 and 37°C. The molecular weight of the enzyme was calculated to be 46,300 dalton from a calibrated Superdex 75 and the subunit molecular weight was estimated at 46,000 dalton by SDS-PAGE. These results suggest that limipterin synthase exists as a monomer. Biosynthetic intermediates of H4-limipterin such as N2NTP , 6-PTP, and H4-biopterin were identified in vitro using purified GTP cyclohydrolase I, PTP synthase, sepiapterin reductase, and limipterin synthase. From the HPLC and TLC analyses of the enzymic intermediater, it could be concluded that H4-limipterin comes from GTP by way of H4-biopterin in Chlorobium limicola.
Electronic Charge Density and Electrostatic Potential of Pterin, 7,8-Dihydropterin and 5,6,7,8-Tetrahydropterin - an Ab initio Quantum Chemical Study
Authors: Reibnegger Gilbert , Horejsi Renate , Oettl Karl , Mlekusch Walter 
Published: March 2013

SummaryAb initio quantum chemical computations at the Hartree-Fock 6-31g** level of theory were performed on pterin, 7,8-dihydropterin and 5,6,7,8 -tetrahydropterin. The resulting electronic charge density functions and the electrostatic potential functions of the molecules are visualized by graphical software. The results demonstrate the profound changes in electronic properties among these structurally closely related compounds. Our contribution may serve as a basis for deeper insight into the molecular characteristics, also of other chemically or biologically important pterin derivatives of different oxidation state.
Neopterin in Bone Banking
Authors: Peters K. M. , Klosterhalfen B. 
Published: March 2013

Summary Not only in blood transfusion, but also in transplantation of allogenous bone, infection of patients with bacteria and especially with virus is possible. Neopterin as an unspecific marker of an activated cellmediated immune response is elevated in fresh viral infection even before antibodies are detectable. Additional determination of neopterin in bone banking can further reduce the already little risk of a still antibody-negative HIV infection in a spongiosa donor. If a first HIV-antibody test is negative and serum neopterin lies within normal range, a second HIV-test six months after operation, which is otherwise obligatory in bone banking today, can be cancelled and the allograft can be given free for transplantation assuming negative results obtained by other screening criteria.
Procalcitonin and Neopterin in Infectious Diseases
Authors: Wiedermann Franz J. , Innerhofer Petra , Margreiter Josef , Fuchs Dietmar , Schobersberger Wolfgang 
Published: March 2013

Summary
Procalcitonin, a new inflammation parameter, has been shown to be markedly increased in patients with severe bacterial and parasitic infections, septic shock, and multiple organ failure. In contrast, in severe viral infections or inflammatory reactions of non-infectious origin (e.g. toxic acute respiratory distress syndrome or toxic pancreatitis) as well as in autoimmune disorders, there is little or moderate increase of procalcitonin serum levels. Therefore procalcitonin may be used for diHerential diagnosis of bacterial versus non-bacterial inflammation. Furthermore, procaicitonin correlates with the severity of infection and sepsis and it is considered to be a valid parameter t()r monitoring both the severity and the course of sepsis and multiple organ failure as well as the success of surgical and intensive therapy in critically ill patients. Neopterin production is closely associated with activation of the cellular immune system. High neopterin levels are found in several inflamlnatory diseases and certain malignancies. Neopterin measurements are useful for monitoring allograft recipients to detect immunological complications. In autoimmune diseases, neopterin concentrations reflect the extent and activity of disease. In infectious diseases, neopterin helps in the differential diagnosis of acute viral and bacterial infections and provides prognostic information in human immunodeficiency virus disease and in patients with multiple trauma and sepsis. In this article the clinical application of procalcitonin and neopterin in infectious diseases is reviewed, and special emphasis is given to clinical situations in which the combined determination of both parameters, neoprerin and procalcitonin, is able to suppon ditkrential diagnosis.
Chronic autoimmune atrophic gastritis associated with primary hyperparathyroidism: a transversal prospective study
Authors: Massironi Sara , Cavalcoli Federica , Rossi Roberta Elisa , Conte Dario , Spampatti Matilde Pia , Ciafardini Clorinda , Verga Uberta , Beck-Peccoz Paolo , Peracchi Maddalena 
Published: February 2013

DesignThe coexistence of chronic autoimmune atrophic gastritis (CAAG) and primary hyperparathyroidism (PHPT) has been described previously, even if its extent and underlying mechanisms remain poorly understood. We therefore prospectively evaluated this association in two series of patients, one with CAAG and the other with sporadic PHPT.MethodsFrom January 2005 to March 2012, 107 histologically confirmed CAAG patients and 149 PHPT patients were consecutively enrolled. Routine laboratory assays included serum calcium, parathyroid hormone (PTH), plasma gastrin and chromogranin A (CgA). In CAAG patients with high PTH levels, ionized calcium and 25(OH)-vitamin D were evaluated. All CAAG and hypergastrinemic PHPT patients received an upper gastrointestinal endoscopy. Exclusion criteria were familial PHPT, MEN1 syndrome, treatment with proton pump inhibitor drugs,Helicobacter pyloriinfection and renal failure.ResultsOf the 107 CAAG patients, nine (8.4%) had PHPT and 13 (12.1%) had secondary hyperparathyroidism stemming from vitamin D deficiency. Among the 149 PHPT patients, 11 (7.4%) had CAAG. Gastrin and CgA levels were similar in the CAAG patients with vs those without hyperparathyroidism (either primary or secondary), and calcium and PTH levels were similar in the PHPT patients with vs those without CAAG.ConclusionsThis study confirms a non-casual association between PHPT and CAAG. The prevalence of PHPT in CAAG patients is threefold that of the general population (8.4 vs 1–3%), and the prevalence of CAAG in PHPT patients is fourfold that of the general population (7.4 vs 2%). The mechanisms underlying this association remain unknown, but a potential role for autoimmunity is suggested.
Modeling Fermi Level Effects in Atomistic Simulations
Authors: Qin Zudian , Dunham Scott T. 
Published: March 2013

AbstractIn this work, variations in electron potential are incorporated into a Kinetic Lattice Monte Carlo (KLMC) simulator and applied to dopant diffusion in silicon. To account for the effect of dopants, the charge redistribution induced by an external point charge immersed in an electron (hole) sea is solved numerically using the quantum perturbation method. The local carrier concentrations are then determined by summing contributions from all ionized dopant atoms and charged point defects, from which the Fermi level of the system is derived by the Boltzmann equation. KLMC simulations with incorporated Fermi level effects are demonstrated for charged point defect concentration as a function of Fermi level, coupled diffusion phenomenon and field effect on doping fluctuations.
Modular Platforms for Optofluidic Systems
Authors: Brammer Marko , Mappes Timo 
Published: February 2013

AbstractOptofluidics is increasingly gaining impact in a number of different fields of research, namely biology and medicine, environmental monitoring and green energy. However, the market for optofluidic products is still in the early development phase. In this manuscript, we discuss modular platforms as a potential concept to facilitate the transfer of optofluidic sensing systems to an industrial implementation. We present microfluidic and optical networks as a basis for the interconnection of optofluidic sensor modules. Finally, we show the potential for entire optofluidic networks
Influence of trace elements supplementation on the production of recombinant frutalin by Pichia pastoris KM71H in fed-batch process
Authors: Wanderley Marcela , Oliveira Carla , Bruneska Danyelly , Domingues Lucília , Lima Filho José , Teixeira José , Mussatto Solange 
Published: March 2013

AbstractFrutalin, a galactose-specific lectin used to detect specific tumour markers, is a protein with low expression level in breadfruit. In the present study, fed-batch fermentation in a stirred tank bioreactor was used as a strategy to enhance protein production by a recombinant Pichia pastoris KM71H. By using this process, the production of recombinant frutalin was 4-fold higher than the value obtained in shaker flasks batch assays. Supplementation of the fermentation medium with trace elements (Pichia trace minerals, PTM) was also evaluated in order to stimulate production of the recombinant protein. The addition of PTM to the minimum medium afforded a recombinant protein production of 13.4 mg L−1, which was 2.5-fold higher than that achieved from the culture medium without PTM supplementation. These results are significant as the development of strategies to improve the production of recombinant frutalin may broaden its application in cancer diagnosis.
Evaluation of temperature effect on growth rate of Lactobacillus rhamnosus GG in milk using secondary models
Authors: Valík Ľubomír , Medveďová Alžbeta , Čižniar Michal , Liptáková Denisa 
Published: March 2013

AbstractThe application of secondary temperature models on growth rates of Lactobacillus rhamnosus GG, the much studied probiotic bacterium, is investigated. Growth parameters resulting from a primary fitting were modelled against temperature using the following models: Hinshelwood model (H), Ratkowsky extended model (RTK2), Zwietering model (ZWT), and cardinal temperature model with inflection (CTMI). As experienced by other authors, the RTK2, ZWT, and CTMI models provided the best statistical indices related to fitting the experimental data. Moreover, with the biological background, the following cardinal temperatures of L. rhamnosus GG resulted from the study by the model application: t min = 2.7°C, t opt = 44.4°C, t max = 52.0°C. The growth rate of the strain under study at optimal temperature was 0.88 log10(CFU mL−1 h−1).
Land plant evolutionary timeline: Gene effects are secondary to fossil constraints in relaxed clock estimation of age and substitution rates
Authors: Magallón Susana , Hilu Khidir W. , Quandt Dietmar 
Published: February 2013

•Premise of the study:Land plants play an essential role in the evolution of terrestrial life. Their time of origin and diversification is fundamental to understanding the evolution of life on land. We investigated the timing and the rate of molecular evolution of land plants, evaluating the effects of different types of molecular data, including temporal information from fossils, and using different molecular clock methods.•Methods:Ages and absolute rates were estimated independently with two substitutionally different data sets: a highly conserved 4‐gene data set andmatK, a fast‐evolving gene. The vascular plant backbone and the crown nodes of all major lineages were calibrated with fossil‐derived ages. Dates and absolute rates were estimated while including or excluding the calibrations and using two relaxed clocks that differ in their implementation of temporal autocorrelation.•Key results:Land plants diverged from streptophyte alga 912 (870–962) million years ago (Mya) but diversified into living lineages 475 (471–480) Mya. Ages estimated for all major land‐plant lineages agree with their fossil record, except for angiosperms. Different genes estimated very similar ages and correlated absolute rates across the tree. Excluding calibrations resulted in the greatest age differences. Different relaxed clocks provided similar ages, but different and uncorrelated absolute rates.•Conclusions:Whole‐genome rate accelerations or decelerations may underlie the similar ages and correlated absolute rates estimated with different genes. We suggest that pronounced substitution rate changes around the angiosperm crown node may represent a challenge for relaxed clocks to model adequately.
Modified leaves with disk‐shaped nectaries of Macaranga sinensis (Euphorbiaceae) provide reward for pollinators
Authors: Yamasaki Eri , Kawakita Atsushi , Sakai Shoko 
Published: February 2013

• Premise of the study: Nectar is the most common reward provided by animal‐pollinated flowers. Diversity in position and structure of floral nectaries suggests that floral nectar production evolved repeatedly, but the evolutionary origins are not well known. Flowers of the genus Macaranga (Euphorbiaceae) are apetalous and lack floral nectar. Nevertheless, many Macaranga species possess disk‐shaped nectaries on their leaves, sought by ants that defend plants from herbivory. In some Macaranga species, similar glands also occur on the bracteoles—modified leaves subtending the flowers. We investigated whether these glands on the bracteoles of M. sinensis are involved in pollination.• Methods: Flower visitors were captured, and body pollen was examined. The behavior of flower visitors on inflorescences was also observed. Sugar composition of the nectar from bracteoles and leaves was collected and analyzed using high‐performance liquid chromatography.• Key results: Various bees and flies with body pollen visited both male and female inflorescences, feeding on nectar from the bracteoles and touching anthers and stigmas in the process. Sugar composition of nectar from the bracteoles and the leaves did not differ.• Conclusions: Macaranga sinensis was pollinated by insects foraging on the disk‐shaped nectaries on bracteoles. The similar appearance, position, and sugar composition of nectar suggest that disk‐shaped nectaries on bracteoles and leaves are homologous and that nectaries on leaves were recruited to inflorescences to serve floral function in M. sinensis. Having protective mutualism with ants has likely opened an unusual route for the evolution of floral nectar in otherwise non‐nectar‐producing flowers of M. sinensis.
Agreement Between the DAS28-CRP Assessed with 3 and 4 Variables in Patients with Rheumatoid Arthritis Treated with Biological Agents in the Daily Clinic
Authors: Madsen Ole Rintek 
Published: March 2013

Objective.The Disease Activity Score-28-C-reactive Protein 4 [DAS28-CRP(4)] composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts, CRP, and patient global assessment. DAS28-CRP(3) includes only 3 variables, because patient global assessment has been omitted. Thresholds for low and high disease activity are the same for the 2 scores. The objective of our study was to compare the 2 DAS scores and their responses on the individual patient level.Methods.Baseline and 12-week disease activity data from 239 patients with RA treated with a biological agent were extracted from the Danish registry for biological treatment (DANBIO). Cohen's effect sizes (ES) and disease activity levels according to the DAS thresholds were assessed. The Bland-Altman method was used to examine the bias between the DAS scores and the 95% limits of agreement (LoA).Results.Baseline values for DAS28-CRP(4) and DAS28-CRP(3) were 4.8 ± 1.2 and 4.6 ± 1.1, respectively. At 12 weeks, DAS28-CRP(4) had improved by −1.39 ± 1.34 (p < 0.0001). At that timepoint the bias of DAS28-CRP(3) was −0.07 (LoA −0.69, 0.55) (p < 0.0001). The bias of the DAS28-CRP(3) response was +0.21 (LoA −0.49, 0.91) (p < 0.0001). ES for DAS28-CRP(4) was 1.2 ± 1.1 versus 1.1 ± 1.1 for DAS28-CRP(3) (p < 0.0001). Compared to DAS28-CRP(4), DAS28-CRP(3) categorized 33% fewer patients as having a high level of disease activity, 8% fewer patients as good responders, and 12% more patients as nonresponders.Conclusion.Mean values of DAS28-CRP(4) and DAS28-CRP(3) agreed well, but in the individual patient the difference between the scores and their responses may be substantial.