Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.

PubMed

Ezzelarab, M B; Zahorchak, A F; Lu, L; Morelli, A E; Chalasani, G; Demetris, A J; Lakkis, F G; Wijkstrom, M; Murase, N; Humar, A; Shapiro, R; Cooper, D K C; Thomson, A W

2013-08-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5-10 × 10(6) /kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on Day -2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n = 6) and 113.5 days (p < 0.05) in DCreg-treated animals (n = 6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95(+) T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further preclinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

PubMed Central

Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

2014-01-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on day −2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n=6) and 113.5 days (p< 0.05) in DCreg-treated animals (n=6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95+ T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further pre-clinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. PMID:23758811

Lentivirus Restriction by Diverse Primate APOBEC3A Proteins

PubMed Central

Schmitt, Kimberly; Guo, Kejun; Katuwal, Miki; Wilson, Darayu; Prochnow, Courtney; Bransteitter, Ronda; Chen, Xiaojiang S.; Santiago, Mario L.; Stephens, Edward B.

2016-01-01

Rhesus macaque APOBEC3A (rhA3A) is capable of restricting both simian-human immunodeficiency virus (SHIVΔvif) and human immunodeficiency virus (HIV-1Δvif) greater extent than hA3A. We constructed chimeric A3A proteins to define the domains required for differential lentivirus restriction. Substitution of amino acids 25–33 from rhA3A into hA3A was sufficient to restrict HIVΔvif to levels similar to rhA3A restriction of SHIVΔvif. We tested if differential lentivirus restriction is conserved between A3A from Old World monkey and hominid lineages. A3A from African green monkey restricted SHIVΔvif but not HIV-1Δvif and colobus monkey A3A restricted both wild type and SHIVΔvif and HIV-1Δvif. In contrast the gibbon ape A3A restricted neither SHIVΔvif nor HIV-1Δvif. Restriction of SHIVΔvif and HIV-1Δvif by New World monkey A3A proteins was not conserved as the A3A from the squirrel monkey but not the northern owl monkey restricted SHIVΔvif. Finally, the colobus A3A protein appears to restrict by a novel post-entry mechanism. PMID:23648232

a Maximum Entropy Model of the Bearded Capuchin Monkey Habitat Incorporating Topography and Spectral Unmixing Analysis

NASA Astrophysics Data System (ADS)

Howard, A. M.; Bernardes, S.; Nibbelink, N.; Biondi, L.; Presotto, A.; Fragaszy, D. M.; Madden, M.

2012-07-01

Movement patterns of bearded capuchin monkeys (Cebus (Sapajus) libidinosus) in northeastern Brazil are likely impacted by environmental features such as elevation, vegetation density, or vegetation type. Habitat preferences of these monkeys provide insights regarding the impact of environmental features on species ecology and the degree to which they incorporate these features in movement decisions. In order to evaluate environmental features influencing movement patterns and predict areas suitable for movement, we employed a maximum entropy modelling approach, using observation points along capuchin monkey daily routes as species presence points. We combined these presence points with spatial data on important environmental features from remotely sensed data on land cover and topography. A spectral mixing analysis procedure was used to generate fraction images that represent green vegetation, shade and soil of the study area. A Landsat Thematic Mapper scene of the area of study was geometrically and atmospherically corrected and used as input in a Minimum Noise Fraction (MNF) procedure and a linear spectral unmixing approach was used to generate the fraction images. These fraction images and elevation were the environmental layer inputs for our logistic MaxEnt model of capuchin movement. Our models' predictive power (test AUC) was 0.775. Areas of high elevation (>450 m) showed low probabilities of presence, and percent green vegetation was the greatest overall contributor to model AUC. This work has implications for predicting daily movement patterns of capuchins in our field site, as suitability values from our model may relate to habitat preference and facility of movement.

Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker.

PubMed

David, Robert; Groebner, Michael; Franz, Wolfgang-Michael

2005-04-01

Embryonic stem (ES) cells offer great potential in regenerative medicine and tissue engineering. Clinical applications are still hampered by the lack of protocols for gentle, high-yield isolation of specific cell types for transplantation expressing no immunogenic markers. We describe labeling of stably transfected ES cells expressing a human CD4 molecule lacking its intracellular domain (DeltaCD4) under control of the phosphoglycerate kinase promoter for magnetic cell sorting (MACS). To track the labeled ES cells, we fused DeltaCD4 to an intracellular enhanced green fluorescent protein domain (DeltaCD4EGFP). We showed functionality of the membrane-bound fluorescent fusion protein and its suitability for MACS leading to purities greater than 97%. Likewise, expression of DeltaCD4 yielded up to 98.5% positive cells independently of their differentiation state. Purities were not limited by the initial percentage of DeltaCD4(+) cells, ranging from 0.6%-16%. The viability of MACS-selected cells was demonstrated by reaggregation and de novo formation of embryoid bodies developing all three germ layers. Thus, expression of DeltaCD4 in differentiated ES cells may enable rapid, high-yield purification of a desired cell type for tissue engineering and transplantation studies.

Neurons with object-centered spatial selectivity in macaque SEF: do they represent locations or rules?

PubMed

Tremblay, Léon; Gettner, Sonya N; Olson, Carl R

2002-01-01

In macaque monkeys performing a task that requires eye movements to the leftmost or rightmost of two dots in a horizontal array, some neurons in the supplementary eye field (SEF) fire differentially according to which side of the array is the target regardless of the array's location on the screen. We refer to these neurons as exhibiting selectivity for object-centered location. This form of selectivity might arise from involvement of the neurons in either of two processes: representing the locations of targets or representing the rules by which targets are selected. To distinguish between these possibilities, we monitored neuronal activity in the SEF of two monkeys performing a task that required the selection of targets by either an object-centered spatial rule or a color rule. On each trial, a sample array consisting of two side-by-side dots appeared; then a cue flashed on one dot; then the display vanished and a delay ensued. Next a target array consisting of two side-by-side dots appeared at an unpredictable location and another delay ensued; finally the monkey had to make an eye movement to one of the target dots. On some trials, the monkey had to select the dot on the same side as the cue (right or left). On other trials, he had to select the target of the same color as the cue (red or green). Neuronal activity robustly encoded the object-centered locations first of the cue and then of the target regardless of the whether the monkey was following a rule based on object-centered location or color. Neuronal activity was at most weakly affected by the type of rule the monkey was following (object-centered-location or color) or by the color of the cue and target (red or green). On trials involving a color rule, neuronal activity was moderately enhanced when the cue and target appeared on opposite sides of their respective arrays. We conclude that the general function of SEF neurons selective for object-centered location is to represent where the cue and target are in their respective arrays rather than to represent the rule for target selection.

Evaluation of heavy metal pollution in water wells and soil using common leafy green plant indicators in the Al-Kharj region, Saudi Arabia.

PubMed

Al-Hammad, Bushra Ahmed; Abd El-Salam, Magda Magdy

2016-06-01

This study was performed to determine the levels of eight heavy metals in irrigation well water and soil and to assess the suitability of some leafy green plants that are commonly cultivated in the Al-Kharj region, Saudi Arabia, for human consumption using an atomic absorption spectrometer. The mean concentrations of metals ranged from 0.0001 to 0.436 mg/L in well water and from 0.248 to 164.52 mg/kg in soil. The heavy metal concentrations showed significant differences among the different leafy green plants studied. Parsley (4.98 mg/kg) exhibited higher levels of Pb than other leafy green plants, whereas mallow (0.097 mg/kg) revealed greater amounts of Cd than other plants. All of the leafy green plants retained essential metals (Cu, Zn, Fe and Mn) more than the toxic metals (Pb and Cd). The levels of some of the metals in the leafy green plants were found to meet the FAO/WHO-recommended limits. The monitoring of heavy metals in leafy green plants must be continued because these plants are the main source of food for humans in many parts of the world and are considered to be bio-indicators for environmental pollution.

The excitonic photoluminescence mechanism and lasing action in band-gap-tunable CdS(1-x)Se(x) nanostructures.

PubMed

Dai, Jun; Zhou, Pengxia; Lu, Junfeng; Zheng, Hongge; Guo, Jiyuan; Wang, Fang; Gu, Ning; Xu, Chunxiang

2016-01-14

Bandgap tunable semiconductor materials have wide application in integrated-optoelectronic and communication devices. The CdS1-xSex ternary semiconductor materials covering green-red bands have been reported previously, but their basic band-gap and optical properties crucial to the performance of the CdS1-xSex-based optoelectronic devices have not been deeply understood. In this paper, we theoretically simulated and discussed the feasibility of bandgap-tunable CdS1-xSex nanomaterials for designing wavelength tunable microlasers. Then we fabricated the CdS1-xSex nanobelts with their band gap ranging from 2.4 to 1.74 eV by adjusting the composition ratio x in the vapor-phase-transport growth process. The temperature-dependent photoluminescence and exciton-related optical constants of the CdS1-xSex nanobelts were carefully demonstrated. Finally, the wavelength-tunable Fabry-Perot lasing in CdS1-xSex nanobelts was obtained, and the Fabry-Perot lasing mechanism was numerically simulated by the FDTD method. The systematic results on the mechanism of the tunable band gap, exciton properties and lasing of the CdS1-xSex nanostructure help us deeply understand the intrinsic optical properties of this material, and will build a strong foundation for future application of green-red wavelength-tunable CdS1-xSex microlasers.

Room temperature ionic liquid-based dispersive liquid phase microextraction for the separation/preconcentration of trace Cd(2+) as 1-(2-pyridylazo)-2-naphthol (PAN) complex from environmental and biological samples and determined by FAAS.

PubMed

Khan, Sumaira; Soylak, Mustafa; Kazi, Tasneem Gul

2013-12-01

The current work develops a new green methodology for the separation/preconcentration of cadmium ions (Cd(2+)) using room temperature ionic liquid-dispersive liquid phase microextraction (RTIL-DLME) prior to analysis by flame atomic absorption spectrometry with microsample introduction system. Room temperature ionic liquids (RTIL) are considered "Green Solvents" for their thermally stable and non-volatile properties, here 1-butyl-3-methylimidazolium hexafluorophosphate [C4mim][PF6] was used as an extractant. The preconcentration of Cd(2+) in different waters and acid digested scalp hair samples were complexed with 1-(2-pyridylazo)-2-naphthol and extracted into the fine drops of RTILs. Some significant factors influencing the extraction efficiency of Cd(2+) and its subsequent determination, including pH, amount of ligand, volume of RTIL, dispersant solvent, sample volume, temperature, and incubation time were investigated in detail. The limit of detection and the enhancement factor under the optimal conditions were 0.05 μg/L and 50, respectively. The relative standard deviation of 100 μg/L Cd(2+) was 4.3 %. The validity of the proposed method was checked by determining Cd(2+) in certified reference material (TM-25.3 fortified water). The sufficient recovery (>98 %) of Cd(2+) with the certified value. The mean concentrations of Cd in lake water 13.2, waste water 15.7 and hair sample 16.8 μg/L, respectively and the developed method was applied satisfactorily to the preconcentration and determination of Cd(2+) in real samples.

Seroprevalence of Zika Virus in Wild African Green Monkeys and Baboons.

PubMed

Buechler, Connor R; Bailey, Adam L; Weiler, Andrea M; Barry, Gabrielle L; Breitbach, Meghan E; Stewart, Laurel M; Jasinska, Anna J; Freimer, Nelson B; Apetrei, Cristian; Phillips-Conroy, Jane E; Jolly, Clifford J; Rogers, Jeffrey; Friedrich, Thomas C; O'Connor, David H

2017-01-01

Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive "sentinel" macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular.

Portulaca grandiflora as green roof vegetation: Plant growth and phytoremediation experiments.

PubMed

Vijayaraghavan, K; Arockiaraj, Jesu; Kamala-Kannan, Seralathan

2017-06-03

Finding appropriate rooftop vegetation may improve the quality of runoff from green roofs. Portulaca grandiflora was examined as possible vegetation for green roofs. Green roof substrate was found to have low bulk density (360.7 kg/m 3 ) and high water-holding capacity (49.4%), air-filled porosity (21.1%), and hydraulic conductivity (5270 mm/hour). The optimal substrate also supported the growth of P. grandiflora with biomass multiplication of 450.3% and relative growth rate of 0.038. Phytoextraction potential of P. grandiflora was evaluated using metal-spiked green roof substrate as a function of time and spiked substrate metal concentration. It was identified that P. grandiflora accumulated all metals (Al, Cd, Cr, Cu, Fe, Ni, Pb, and Zn) from metal-spiked green roof substrate. At the end of 40 days, P. grandiflora accumulated 811 ± 26.7, 87.2 ± 3.59, 416 ± 15.8, 459 ± 15.6, 746 ± 20.9, 357 ± 18.5, 565 ± 6.8, and 596 ± 24.4 mg/kg of Al, Cd, Cr, Cu, Fe, Ni, Pb and Zn, respectively. Results also indicated that spiked substrate metal concentration strongly influenced metal accumulation property of P. grandiflora with metal uptake increased and accumulation factor decreased with increase in substrate metal concentration. P. grandiflora also showed potential to translocate all the examined metals with translocation factor greater than 1 for Al, Cu, Fe, and Zn, indicating hyperaccumulation property.

Effect of Background Luminance Level on the Assessment of Color Visual Acuity Using Colored Landolt Rings in Young Healthy Subjects.

PubMed

Tanaka, Yoshiki; Yokoyama, Sho; Horai, Rie; Kojima, Takashi; Hiroyuki, Sato; Kato, Yukihito; Takagi, Mari; Nakamura, Hideki; Tanaka, Kiyoshi; Ichikawa, Kazuo; Tanabe, Shoko

2018-03-01

To evaluate the color visual acuity (CVA) of young healthy subjects using colored Landolt rings and the effect of background luminance level on the CVA. We measured the CVA of 20 young healthy subjects (age: 23.8 ± 3.8 years) with different colors using a computer and a liquid crystal display, with 15 Landolt ring colors (30 cd/m 2 ) with a background luminance of 30 cd/m 2 , and then 100 cd/m 2 . We then used different background luminance levels (15-50 cd/m 2 ) using four Landolt ring colors (red, green-yellow, green, and blue-green) to evaluate the effect of the background luminance level on CVA. The CVA significantly differed among the colors with a background luminance of 30 cd/m 2 (p < 0.0001). Green-yellow and blue-purple had poor CVA (high LogMAR value; 0.808 ± 0.107 and 0.633 ± 0.150, respectively) with a background luminance of 30 cd/m 2 (same luminance as the Landolt rings). There were no significant differences in the CVAs among the colors with a background luminance of 100 cd/m 2 (p = 0.5999). There were no significant difference in the CVA between background luminance 30 cd/m 2 and other luminance level ranging from 28 to 32 cd/m 2 for colors of red, green-yellow, green, and blue-green. The results reveal that the background luminance of Landolt rings affects the CVA. Distinctive CVAs for each color are measured by equalizing the luminance between the Landolt ring and the background. We consider that the poor CVAs of these colors reflect the visual function of S-cone, because GY and BP are included in the confusion locus of tritan axis on the chromaticity diagram. We believe that CVA assessment may be useful for individuals who have known or suspected ocular dysfunction or color vision deficiencies.

Unusual antigen presentation offers new insight into HIV vaccine design.

PubMed

McMichael, Andrew J; Picker, Louis J

2017-06-01

Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Use of acidophilic bacteria of the genus Acidithiobacillus to biosynthesize CdS fluorescent nanoparticles (quantum dots) with high tolerance to acidic pH".

PubMed

Ulloa, G; Collao, B; Araneda, M; Escobar, B; Álvarez, S; Bravo, D; Pérez-Donoso, J M

2016-12-01

The use of bacterial cells to produce fluorescent semiconductor nanoparticles (quantum dots, QDs) represents a green alternative with promising economic potential. In the present work, we report for the first time the biosynthesis of CdS QDs by acidophilic bacteria of the Acidithiobacillus genus. CdS QDs were obtained by exposing A. ferrooxidans, A. thiooxidans and A. caldus cells to sublethal Cd 2+ concentrations in the presence of cysteine and glutathione. The fluorescence of cadmium-exposed cells moves from green to red with incubation time, a characteristic property of QDs associated with nanocrystals growth. Biosynthesized nanoparticles (NPs) display an absorption peak at 360nm and a broad emission spectra between 450 and 650nm when excited at 370nm, both characteristic of CdS QDs. Average sizes of 6 and 10nm were determined for green and red NPs, respectively. The importance of cysteine and glutathione on QDs biosynthesis in Acidithiobacillus was related with the generation of H 2 S. Interestingly, QDs produced by acidophilic bacteria display high tolerance to acidic pH. Absorbance and fluorescence properties of QDs was not affected at pH 2.0, a condition that totally inhibits the fluorescence of QDs produced chemically or biosynthesized by mesophilic bacteria (stable until pH 4.5-5.0). Results presented here constitute the first report of the generation of QDs with improved properties by using extremophile microorganisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Origin of luminescence from ZnO/CdS core/shell nanowire arrays

NASA Astrophysics Data System (ADS)

Wang, Zhiqiang; Wang, Jian; Sham, Tsun-Kong; Yang, Shaoguang

2014-07-01

Chemical imaging, electronic structure and optical properties of ZnO/CdS nano-composites have been investigated using scanning transmission X-ray microscopy (STXM), X-ray absorption near-edge structure (XANES) and X-ray excited optical luminescence (XEOL) spectroscopy. STXM and XANES results confirm that the as-prepared product is ZnO/CdS core/shell nanowires (NWs), and further indicate that ZnS was formed on the surface of ZnO NWs as the interface between ZnO and CdS. The XEOL from ZnO/CdS NW arrays exhibits one weak ultraviolet (UV) emission at 375 nm, one strong green emission at 512 nm, and two broad infrared (IR) emissions at 750 and 900 nm. Combining XANES and XEOL, it is concluded that the UV luminescence is the near band gap emission (BGE) of ZnO; the green luminescence comes from both the BGE of CdS and defect emission (DE, zinc vacancies) of ZnO; the IR luminescence is attributed to the DE (bulk defect related to the S site) of CdS; ZnS contributes little to the luminescence of the ZnO/CdS NW arrays. Interestingly, the BGE and DE from oxygen vacancies of ZnO in the ZnO/CdS nano-composites are almost entirely quenched, while DE from zinc vacancies changes little.Chemical imaging, electronic structure and optical properties of ZnO/CdS nano-composites have been investigated using scanning transmission X-ray microscopy (STXM), X-ray absorption near-edge structure (XANES) and X-ray excited optical luminescence (XEOL) spectroscopy. STXM and XANES results confirm that the as-prepared product is ZnO/CdS core/shell nanowires (NWs), and further indicate that ZnS was formed on the surface of ZnO NWs as the interface between ZnO and CdS. The XEOL from ZnO/CdS NW arrays exhibits one weak ultraviolet (UV) emission at 375 nm, one strong green emission at 512 nm, and two broad infrared (IR) emissions at 750 and 900 nm. Combining XANES and XEOL, it is concluded that the UV luminescence is the near band gap emission (BGE) of ZnO; the green luminescence comes from both the BGE of CdS and defect emission (DE, zinc vacancies) of ZnO; the IR luminescence is attributed to the DE (bulk defect related to the S site) of CdS; ZnS contributes little to the luminescence of the ZnO/CdS NW arrays. Interestingly, the BGE and DE from oxygen vacancies of ZnO in the ZnO/CdS nano-composites are almost entirely quenched, while DE from zinc vacancies changes little. Electronic supplementary information (ESI) available: PL spectra of the ZnO NW arrays before/after CdS coating. S K-edge XANES spectra of the ZnO/CdS core/shell NW arrays. See DOI: 10.1039/c4nr02231a

Persistent infection of macaques with simian-human immunodeficiency viruses.

PubMed Central

Li, J T; Halloran, M; Lord, C I; Watson, A; Ranchalis, J; Fung, M; Letvin, N L; Sodroski, J G

1995-01-01

Chimeric simian-human immunodeficiency viruses (SHIV) containing the human immunodeficiency virus type 1 (HIV-1) tat, rev, env, and, in some cases, vpu genes were inoculated into eight cynomolgus monkeys. Viruses could be consistently recovered from the CD8-depleted peripheral blood lymphocytes of all eight animals for at least 2 months. After this time, virus isolation varied among the animals, with viruses continuing to be isolated from some animals beyond 600 days after inoculation. The level of viral RNA in plasma during acute infection and the frequency of virus isolation after the initial 2-month period were higher for the Vpu-positive viruses. All of the animals remained clinically healthy, and the absolute numbers of CD4-positive lymphocytes were stable. Antibodies capable of neutralizing HIV-1 were generated at high titers in animals exhibiting the greatest consistency of virus isolation. Strain-specific HIV-1-neutralizing antibodies were initially elicited, and then more broadly neutralizing antibodies were elicited. env sequences from two viruses isolated more than a year after infection were analyzed. In the Vpu-negative SHIV, for which virus loads were lower, a small amount of env variation, which did not correspond to that found in natural HIV-1 variants, was observed. By contrast, in the Vpu-positive virus, which was consistently isolated from the host animal, extensive variation of the envelope glycoproteins in the defined variable gp120 regions was observed. Escape from neutralization by CD4 binding site monoclonal antibodies was observed for the viruses with the latter envelope glycoproteins, and the mechanism of escape appears to involve decreased binding of the antibody to the monomeric gp120 glycoproteins. The consistency with which SHIV infection of cynomolgus monkeys is initiated and the similarities in the neutralizing antibody response to SHIV and HIV-1 support the utility of this model system for the study of HIV-1 prophylaxis. PMID:7474126

Development of Alouattamyia baeri (Diptera: Oestridae) from howler monkeys (Primates: Cebidae) on Barro Colorado Island, Panama.

PubMed

Colwell, D D; Milton, K

1998-09-01

The fecundity and development of larval stages of the cuterebrid bot fly A. baeri were studied in an unusual host, remotely related to the primary host. Third-instar Alouattamyia baeri (Shannon & Greene) removed from howler monkeys, Alouatta palliata, were allowed to pupate and then were cultured under controlled conditions. Eclosion occurred after 37.9 +/- 0.4 (mean +/- SE) (male) and 38.2 +/- 0.4 (female) d at 26 degrees C. Five-day-old females were mated using a tethered flight technique and oviposited on ridged filter paper. The total egg complement was 1,399 +/- 243 (n = 2) eggs per female. Eggs were fully embryonated after incubation for 5 d at 26 degrees C. Eggs hatched when warmed in the palm of the hand. Hatching of eggs from an individual batch was asynchronous. Newly hatched larvae would not penetrate intact skin on a rabbit, Oryctolagus cuniculus L. Larvae placed near the nares or on the ocular conjunctiva migrated rapidly from view. Warbles containing larvae were first observed on infested rabbits 5 d after infestation. Development of larvae proceeded until day 39 after infestation, when nearly mature 3rd instars were observed. None of the larvae survived to pupate.

Direct comparison of (+/-) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans.

PubMed

Mueller, Melanie; Kolbrich, Erin A; Peters, Frank T; Maurer, Hans H; McCann, Una D; Huestis, Marilyn A; Ricaurte, George A

2009-06-01

The present study compared the disposition and metabolism of the recreational drug (+/-) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4-methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

Fabrication of white light-emitting diodes based on UV light-emitting diodes with conjugated polymers-(CdSe/ZnS) quantum dots as hybrid phosphors.

PubMed

Jung, Hyunchul; Chung, Wonkeun; Lee, Chang Hun; Kim, Sung Hyun

2012-07-01

White light-emitting diodes (LEDs) were fabricated using GaN-based 380-nm UV LEDs precoated with the composite of blue-emitting polymer (poly[(9,9-dihexylfluorenyl-2,7-diyl)-alt-co-(2-methoxy-5-{2-ethylhexyloxy)-1 ,4-phenylene)]), yellow green-emitting polymer (poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadiazole)]), and 605-nm red-emitting quantum dots (QDs). CdSe cores were obtained by solvothermal route using CdO, Se precursors and ZnS shells were synthesized by using diethylzinc, and hexamethyldisilathiane precursors. The optical properties of CdSe/ZnS QDs were characterized by UV-visible and photoluminescence (PL) spectra. The structural data and composition of the QDs were transmission electron microscopy (TEM), and EDX technique. The quantum yield and size of the QDs were 58.7% and about 6.7 nm, respectively. Three-band white light was generated by hybridizing blue (430 nm), green (535 nm), and red (605 nm) emission. The color-rendering index (CRI) of the device was extremely improved by introducing the QDs. The CIE-1931 chromaticity coordinate, color temperature, and CRI of a white LED at 20 mA were (0.379, 0.368), 3969 K, and 90, respectively.

Remediation and reclamation of soils heavily contaminated with toxic metals as a substrate for greening with ornamental plants and grasses.

PubMed

Jelusic, Masa; Lestan, Domen

2015-11-01

Soils highly contaminated with toxic metals are currently treated as waste despite their potential inherent fertility. We applied EDTA washing technology featuring chelant and process water recovery for remediation of soil with 4037, 2527, and 26 mg kg(-1) of Pb, Zn and Cd, respectively in a pilot scale. A high EDTA dose (120 mmol kg(-1) of soil) removed 70%, 15%, and 58% of Pb, Zn, and Cd, respectively, and reduced human oral bioaccessibility of Pb below the limit of quantification and that of Zn and Cd 3.4 and 3.2 times. In a lysimeters experiment, the contaminated and remediated soils were laid into two garden beds (4×1×0.15 m) equipped with lysimeters, and subjected to cultivation of ornamental plants: Impatiens walleriana, Tagetes erecta, Pelargonium×peltatum, and Verbena×hybrida and grasses: Dactylis glomerata, Lolium multiflorum, and Festuca pratensis. Plants grown on remediated soil demonstrated the same or greater biomass yield and reduced the uptake of Pb, Zn and Cd up to 10, 2.5 and 9.5 times, respectively, compared to plants cultivated on the original soil. The results suggest that EDTA remediation produced soil suitable for greening. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation of Yellow-Green-Emissive Carbon Dots and Their Application in Constructing a Fluorescent Turn-On Nanoprobe for Imaging of Selenol in Living Cells.

PubMed

Wang, Qin; Zhang, Shengrui; Zhong, Yaogang; Yang, Xiao-Feng; Li, Zheng; Li, Hua

2017-02-07

Selenocysteine (Sec) carries out the majority of the functions of the various Se-containing species in vivo. Thus, it is of great importance to develop sensitive and selective assays to detect Sec. Herein, a carbon-dot-based fluorescent turn-on probe for highly selective detection of selenol in living cells is presented. The highly photoluminescent carbon dots that emit yellow-green fluorescence (Y-G-CDs; λ max = 520 nm in water) were prepared by using m-aminophenol as carbon precursor through a facile solvothermal method. The surface of Y-G-CDs was then covalently functionalized with 2,4-dinitrobenzenesulfonyl chloride (DNS-Cl) to afford the 2,4-dinitrobenzene-functionalized CDs (CD-DNS) as a nanoprobe for selenol. CD-DNS is almost nonfluorescent. However, upon treating with Sec, the DNS moiety of CD-DNS can be readily cleaved by selenolate through a nucleophilic substitution process, resulting in the formation of highly fluorescent Y-G-CDs and hence leads to a dramatic increase in fluorescence intensity. The proposed nanoprobe exhibits high sensitivity and selectivity toward Sec over biothiols and other biological species. A preliminary study shows that CD-DNS can function as a useful tool for fluorescence imaging of exogenous and endogenous selenol in living cells.

Trichromacy increases fruit intake rates of wild capuchins (Cebus capucinus imitator)

PubMed Central

Chiou, Kenneth L.; Walco, Emily R.; Bergstrom, Mackenzie L.; Kawamura, Shoji; Fedigan, Linda M.

2017-01-01

Intraspecific color vision variation is prevalent among nearly all diurnal monkeys in the neotropics and is seemingly a textbook case of balancing selection acting to maintain genetic polymorphism. Clear foraging advantages to monkeys with trichromatic vision over those with dichromatic “red-green colorblind” vision have been observed in captive studies; however, evidence of trichromatic advantage during close-range foraging has been surprisingly scarce in field studies, perhaps as a result of small sample sizes and strong impacts of environmental or individual variation on foraging performance. To robustly test the effects of color vision type on foraging efficiency in the wild, we conducted an extensive study of dichromatic and trichromatic white-faced capuchin monkeys (Cebus capucinus imitator), controlling for plant-level and monkey-level variables that may affect fruit intake rates. Over the course of 14 months, we collected behavioral data from 72 monkeys in Sector Santa Rosa, Costa Rica. We analyzed 19,043 fruit feeding events within 1,602 foraging bouts across 27 plant species. We find that plant species, color conspicuity category, and monkey age class significantly impact intake rates, while sex does not. When plant species and age are controlled for, we observe that trichromats have higher intake rates than dichromats for plant species with conspicuously colored fruits. This study provides clear evidence of trichromatic advantage in close-range fruit feeding in wild monkeys. Taken together with previous reports of dichromatic advantage for finding cryptic foods, our results illuminate an important aspect of balancing selection maintaining primate opsin polymorphism. PMID:28894009

Species and sex differences in susceptibility to olfactory lesions among the mouse, rat and monkey following an intravenous injection of vincristine sulphate.

PubMed

Kai, Kiyonori; Sahto, Hiroshi; Yoshida, Mitsuyoshi; Suzuki, Takami; Shikanai, Yukari; Kajimura, Tetsuyo; Furuhama, Kazuhisa

2006-01-01

Species and sex differences in susceptibility to vincristine sulphate (VCR)-induced olfactory epithelial lesions were investigated among the BALB/c mice, Crj: CD(SD) IGS rats and common marmoset monkeys following a single intravenous administration on day 1. As dosage levels, the 0.17-fold LD10, 0.6-fold LD10 and LD10 were used for mice and rats, and a maximum tolerated dose (MTD) was chosen only for monkeys. The order of strength of VCR action on peripheral neuropathic signs, body weight gain, and hematological parameters was mice > rats > monkeys, without clear sex differences. Histopathologically, on day 2, single cell death in the olfactory epithelium and vomeronasal organ was observed only in male mice at LD10, and in female mice at 0.6-fold LD10 or more. On day 5, the olfactory epithelium in these mice showed regenerative proliferation suggesting a sign of recovery. On day 10, axonopathy and demyelination in the sciatic and trigeminal nerves were noted in mice of both sexes at 0.6-fold LD10 or more. In rats and monkeys of either sex, however, no morphological changes were observed at any dose level. In conclusion, mice, particularly females, were shown to be more susceptible to VCR-induced apoptosis in the olfactory epithelium than rats and monkeys.

Green Synthesis of Cyclodextrin-Based Metal-Organic Frameworks through the Seed-Mediated Method for the Encapsulation of Hydrophobic Molecules.

PubMed

Qiu, Chao; Wang, Jinpeng; Qin, Yang; Fan, Haoran; Xu, Xueming; Jin, Zhengyu

2018-04-25

Metal-organic frameworks (MOFs) are attracting considerable attention as a result of their unique structural properties, such as a high surface area, highly porous topology, and tunable size and shape, which enable them to have potential applications as a new class of carriers for functional agent or drug delivery. However, most of the MOFs and the polymers used are not pharmaceutically acceptable. For the first time, this study successfully conducted the rapid synthesis of cyclodextrin metal-organic frameworks (CD-MOFs) through a facile and green seed-mediated method. The size control, crystal structure, and thermal properties of CD-MOFs with and without seeds were investigated. When 1 mg/mL seed was added, the size of γ-CD-MOF crystals decreased from 6.2 ± 0.8 to 1.8 ± 0.4 μm. The CD-MOFs synthesized though the seed-mediated method had higher crystallinity and thermal stability than those that were not. Furthermore, the CD-MOFs could encapsulate hydrophobic molecules, such as Nile red (NR), which was chosen as a model, and the interaction mechanism between γ-CD-MOFs and NR was investigated. Results showed the formation of a 1:1 complex between NR and CD-MOFs, demonstrating the potential of these polymers as carriers for hydrophobic drug delivery applications.

Permethylated-β-Cyclodextrin Capped CdTe Quantum Dot and its Sensitive Fluorescence Analysis of Malachite Green.

PubMed

Cao, Yujuan; Wei, Jiongling; Wu, Wei; Wang, Song; Hu, Xiaogang; Yu, Ying

2015-09-01

In the present work, the CdTe quantum dots were covalently conjugated with permethylated-β-cyclodextrin (OMe-β-CD) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as cross-linking reagent. The obtained functional quantum dots (OMe-β-CD/QDs) showed highly luminescent, water solubility and photostability as well as good inclusion ability to malachite green. A sensitive fluorescence method was developed for the analysis of malachite green in different samples. The good linearity was 2.0 × 10(-7)-1.0 × 10(-5) mol/L and the limit of detect was 1.7 × 10(-8) mol/L. The recoveries for three environmental water samples were 92.0-108.2 % with relative standard deviation (RSD) of 0.24-1.87 %, while the recovery for the fish sample was 94.3 % with RSD of 1.04 %. The results showed that the present method was sensitive and convenient to determine malachite green in complex samples. Graphical Abstract The analytical mechanism of OMe-β-CD/QDs and its linear response to MG.

New cadmium(II) halides modified by N-heterocyclic molecules

NASA Astrophysics Data System (ADS)

Wang, Tie-Gang; Li, Su; Yu, Jie-Hui; Xu, Ji-Qing

2015-03-01

Under the solvothermal condition, the reaction of CdI2, bpp and KI at pH = 8 afforded compound [CdI2(bpp)] (bpp = 1,2-bis(4-pyridyl)propane) 1, while at the ambient conditions, the reactions of CdX2, dabco and KX at pH = 4-5 produced compounds [H2(dabco)][CdBr4]·H2O (dabco = 1,4-diazabicyclo[2,2,2]octane) 2 and [(Hdabco)CdI3] 3. X-ray single-crystal diffraction analysis reveals that (i) compound 1 possesses a one-dimensional (1-D) zigzag chain structure. The large volume bpp molecule controls the Cd2+ ion to adopt a tetrahedral geometric configuration; (ii) both compounds 2 and 3 are mononuclear. Interestingly, in the same pH environments, dabco was in situ diprotonated in compound 2, while dabco was in situ monoprotonated in compound 3. The templating effect as well as the X- ion maybe plays a key role in the protonated degree for dabco in an acidic environment. The photoluminescence analysis indicates that compound 1 emits the strong green light, which should be attributed to a combination of two types of charge transfers: the charge transfer between Cd2+ and I-; the charge transfer between Cd2+ and bpp.

Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

PubMed

Peng, Wei; Ding, Fei; Peng, Yu-Kui; Sun, Ying

2014-01-01

Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as π-π interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the α-helix and increase of the β-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green.

Characterization of alpha(4)beta(1) (CD49d/CD29) on equine leukocytes: potential utility of a potent alpha(4)beta(1) (CD49d/CD29) receptor antagonist in the treatment of equine heaves (recurrent airway obstruction).

PubMed

Treonze, Kelly M; Alves, Kenneth; Fischer, Paul; Hagmann, William K; Hora, Donald; Kulick, Alison; Vakerich, Ken; Smith, Nicholas D; Lingham, Russell B; Maniar, Salony; Reger, Thomas S; Zunic, Jasmine; Munoz, Benito; Prasit, Peppi; Nicholson, Donald; Si, Qian; Judd, Keith; Nicolich, Susan; Kellerhouse, Patricia; Thompson, Donald; Mumford, Richard A

2009-07-15

The purpose of this study was to characterize the alpha(4)beta(1) receptor (CD49d/CD29, very late antigen-4, VLA-4) on circulating equine leukocytes and to evaluate the intrinsic potency of an alpha(4)beta(1) receptor antagonist (Compound B) in the horse. Ultimately, these studies would allow us to determine the suitability of treating recurrent airway obstruction (RAO; heaves) affected horses by blocking the cellular recruitment of lymphocytes and neutrophils into the lung. The data demonstrates the alpha(4)beta(1) integrin is present on horse lymphocytes and neutrophils (fluorescence-assisted cell sorter, FACS) and can bind low molecular weight alpha(4)beta(1) antagonists (Compounds A and B) with high affinity. K(D) values for the binding of Compound A to non-activated alpha(4)beta(1) on isolated horse PBMCs (peripheral blood mononuclear cells) and activated neutrophils were 17 pM and 27 pM, respectively. Compound B was identified as a suitable antagonist for performing a series of in vivo experiments. Compound B was found to possess excellent potency in horse whole blood, possessing IC(50) and IC(90) values of 39 pM and 172 pM, respectively. This represents a 3.9-fold molar excess of drug over the alpha(4)beta(1) concentration in blood. Following oral administration of Compound B (5 mg/kg) to beagle dogs and rhesus monkeys, rapid and sustained alpha(4)beta(1) receptor occupancy (>80%) was achieved and maintained for a period of 24 h. When Compound B was administered intravenously to the horse, by either a slow or rapid infusion at a dose of 0.3 mg/kg, receptor blockade of >80% was observed out to 24 h with a concomitant leukocytosis. We believe that Compound B possesses suitable intrinsic and pharmacological properties to be evaluated clinically in horses affected by RAO.

Synthesis, spectroscopic properties, molecular docking, anti-colon cancer and anti-microbial studies of some novel metal complexes for 2-amino-4-phenylthiazole derivative

NASA Astrophysics Data System (ADS)

Al-Harbi, Sami A.; Bashandy, Mahmoud S.; Al-Saidi, Hammed M.; Emara, Adel A. A.; Mousa, Tarek A. A.

2015-06-01

This article describes the synthesis of novel bidentate Schiff base (H2L) from condensation of 2-amino-4-phenylthiazole (APT) with 4,6-diacetylresorcinol (DAR) in the molar ratio 2:1. We studied interaction of ligand (H2L) with transition metal ions such as Cr(III), Fe(III), Cu(II), Zn(II) and Cd(II). The ligand (H2L) has two bidentate sets of (N-O) units which can coordinate with two metal ions to afford novel binuclear metal complexes. The directions of coordinate bonds are from nitrogen atoms of azomethine groups and oxygen atoms of the phenolic groups. Structures of the newly synthesized complexes were confirmed by elemental analysis, IR, UV, 1H NMR, ESR, TGA and mass spectral data. All of the newly synthesized complexes were evaluated for their antibacterial and anti-fungal activities. They were also evaluated for their in vitro anticancer activity against human colon carcinoma cells (HCT-116) and mammalian cells of African green monkey kidney (VERO). The Cu(II) complex with selectivity index (S.I.) = 21.26 exhibited better activity than methotrexate (MTX) as a reference drug with S.I. value = 13.30, while Zn(II) complex with S.I. value = 10.24 was found to be nearly as active as MTX. Molecular docking studies further helped in understanding the mode of action of the compounds through their various interactions with active sites of dihydrofolate reductase (DHFR) enzyme. The observed activity of Fe(III) and Cu(II) complexes gave rise to the conclusion that they might exert their action through inhibition of the DHFR enzyme.

Synthesis, spectroscopic properties, molecular docking, anti-colon cancer and anti-microbial studies of some novel metal complexes for 2-amino-4-phenylthiazole derivative.

PubMed

Al-Harbi, Sami A; Bashandy, Mahmoud S; Al-Saidi, Hammed M; Emara, Adel A A; Mousa, Tarek A A

2015-06-15

This article describes the synthesis of novel bidentate Schiff base (H2L) from condensation of 2-amino-4-phenylthiazole (APT) with 4,6-diacetylresorcinol (DAR) in the molar ratio 2:1. We studied interaction of ligand (H2L) with transition metal ions such as Cr(III), Fe(III), Cu(II), Zn(II) and Cd(II). The ligand (H2L) has two bidentate sets of (N-O) units which can coordinate with two metal ions to afford novel binuclear metal complexes. The directions of coordinate bonds are from nitrogen atoms of azomethine groups and oxygen atoms of the phenolic groups. Structures of the newly synthesized complexes were confirmed by elemental analysis, IR, UV, (1)H NMR, ESR, TGA and mass spectral data. All of the newly synthesized complexes were evaluated for their antibacterial and anti-fungal activities. They were also evaluated for their in vitro anticancer activity against human colon carcinoma cells (HCT-116) and mammalian cells of African green monkey kidney (VERO). The Cu(II) complex with selectivity index (S.I.)=21.26 exhibited better activity than methotrexate (MTX) as a reference drug with S.I. value=13.30, while Zn(II) complex with S.I. value=10.24 was found to be nearly as active as MTX. Molecular docking studies further helped in understanding the mode of action of the compounds through their various interactions with active sites of dihydrofolate reductase (DHFR) enzyme. The observed activity of Fe(III) and Cu(II) complexes gave rise to the conclusion that they might exert their action through inhibition of the DHFR enzyme. Copyright © 2015 Elsevier B.V. All rights reserved.

Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys

PubMed Central

Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias

2013-01-01

Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

Trace element accumulation in hawksbill turtles (Eretmochelys imbricata) and green turtles (Chelonia mydas) from Yaeyama Islands, Japan.

PubMed

Anan, Y; Kunito, T; Watanabe, I; Sakai, H; Tanabe, S

2001-12-01

Concentrations of 18 trace elements (V, Cr, Mn, Co, Cu, Zn, Se, Rb, Sr, Zr, Mo, Ag, Cd, Sb, Ba, Hg, Tl, and Pb) were determined in the liver, kidney, and muscle of green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) from Yaeyama Islands, Okinawa, Japan. Accumulation features of trace elements in the three tissues were similar between green and hawksbill turtles. No gender differences in trace element accumulation in liver and kidney were found for most of the elements. Significant growth-dependent variations were found in concentrations of some elements in tissues of green and hawksbill turtles. Significant negative correlations (p < 0.05) were found between standard carapace length (SCL) and the concentrations of Cu, Zn, and Se in the kidney and V in muscle of green turtles and Mn in the liver, Rb and Ag in kidney, and Hg in muscle of hawksbill turtles. Concentrations of Sr, Mo, Ag, Sb, and Tl in the liver, Sb in kidney, and Sb and Ba in muscle of green turtles and Se and Hg in the liver and Co, Se, and Hg in kidney of hawksbill turtles increased with an increase in SCL (p < 0.05). Green and hawksbill turtles accumulated extremely high concentrations of Cu in the liver and Cd in kidney, whereas the levels of Hg in liver were low in comparison with those of other higher-trophic-level marine animals. High accumulation of Ag in the liver of green turtles was also observed. To evaluate the trophic transfer of trace elements, concentrations of trace elements were determined in stomach contents of green and hawksbill turtles. A remarkably high trophic transfer coefficient was found for Ag and Cd in green turtles and for Cd and Hg in hawksbill turtles.

Differential effects of Denileukin Diftitox IL-2 immunotoxin on NK and regulatory T cells in non-human primates

PubMed Central

Yamada, Yohei; Aoyama, Akihiro; Tocco, Georges; Boskovic, Svjetlan; Nadazdin, Ognjenka; Alessandrini, Alessandro; Madsen, Joren C.; Cosimi, A. Benedict; Benichou, Gilles; Kawai, Tatsuo

2012-01-01

Denileukin Diftitox (DD), a fusion protein comprised of IL-2 and diphtheria toxin was initially expected to enhance anti-tumor immunity by selectively eliminating regulatory T cells (Tregs) displaying the high affinity IL-2R (α-β-γ trimers). While DD has been shown to deplete some Tregs in primates, its effects on NK cells (CD16+CD8+NKG2A+CD3−), which constitutively express the intermediate affinity IL-2R (β-γ dimers) and play a critical role in anti-tumor immunity, are still unknown. To address this question, cynomolgus monkeys were injected intravenously with two different doses of DD (8 or 18 μg/Kg). This treatment resulted in a rapid but short-term reduction in detectable peripheral blood resting Tregs (R-Tregs: CD4+CD45RA+Foxp3+) and a transient increase in the number of activated Tregs (A-Tregs: CD4+CD45RA−Foxp3high) followed by their partial depletion (50–60%). On the other hand, all NK cells were deleted immediately and durably after DD administration. This difference was not due to a higher binding or internalization of DD by NK cells as compared to Tregs. Co-administration of DD with IL-15, which binds to IL-2Rβ-γ, abrogated DD-induced NK cell deletion in vitro and in vivo while it did not affect Tregs elimination. Taken together, these results show that DD exerts a potent cytotoxic effect on NK cells, a phenomenon which might impair its anti-tumoral properties. However, co-administration of IL-15 with DD could alleviate this problem by selectively protecting potentially oncolytic NK cells while allowing the depletion of immunosuppressive regulatory T cells in cancer patients. PMID:22586034

Change Detection by Rhesus Monkeys (Macaca mulatta) and Pigeons (Columba livia)

PubMed Central

Elmore, L. Caitlin; Magnotti, John F.; Katz, Jeffrey S.; Wright, Anthony A.

2012-01-01

Two monkeys learned a color change-detection task where two colored circles (selected from a 4-color set) were presented on a 4×4 invisible matrix. Following a delay, the correct response was to touch the changed colored circle. The monkeys' learning, color transfer, and delay transfer were compared to a similar experiment with pigeons. Monkeys, like pigeons, showed full transfer to four novel colors, and to delays as long as 6.4 s, suggesting they remembered the colors as opposed to perceptual based attentional capture process that may work at very short delays. The monkeys and pigeons were further tested to compare transfer to other dimensions. Monkeys transferred to shape and location changes, unlike the pigeons, but neither species transferred to size changes. Thus, monkeys were less restricted in their domain to detect change than pigeons, but both species learned the basic task and appear suitable for comparative studies of visual short-term memory. PMID:22428982

Hormone suppression with GnRH antagonist promotes spermatogenic recovery from transplanted spermatogonial stem cells in irradiated cynomolgus monkeys.

PubMed

Shetty, G; Uthamanthil, R K; Zhou, W; Shao, S H; Weng, C C; Tailor, R C; Hermann, B P; Orwig, K E; Meistrich, M L

2013-11-01

Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin-releasing hormone antagonist (GnRH-ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein-lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH-ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham-transplanted testes of GnRH-ant-treated monkeys compared with radiation-only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation-only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH-ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH-ant-treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham-transplanted testes and/or to the transplanted testes of the radiation-only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation-only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH-ant-treated monkeys and (iv) significantly higher sperm counts than in the radiation-only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment. © 2013 American Society of Andrology and European Academy of Andrology.

Enhanced Emission Efficiency in Organic Light-Emitting Diodes Using Deoxyribonucleic Acid Complex as an Electron Blocking Layer

DTIC Science & Technology

2006-04-28

1. Color online Photographs of EL emission from several devices: a green Alq3 baseline OLED at 25 V 707 mA/cm2—590 cd/m2, 0.35 cd/A; b green... Alq3 BioLED with DNA EBL at 25 V 308 mA/cm2—21 100 cd/m2, 6.56 cd/A; c blue NPB baseline OLED at 20 V 460 mA/cm2—700 cd/m2, 0.14 cd/A; d blue...al. Appl. Phys. Lett. 88, 171109 2006NPB N ,N-bisnaphthalene-1-yl-N ,N-bisphenyl benzi- dine hole transport layer HTL; Alq3 tris-8

Coffee-Ring-Free Quantum Dot Thin Film Using Inkjet Printing from a Mixed-Solvent System on Modified ZnO Transport Layer for Light-Emitting Devices.

PubMed

Jiang, Congbiao; Zhong, Zhiming; Liu, Baiquan; He, Zhiwei; Zou, Jianhua; Wang, Lei; Wang, Jian; Peng, JunBiao; Cao, Yong

2016-10-05

Inkjet printing has been considered an available way to achieve large size full-color RGB quantum dots LED display, and the key point is to obtain printed film with uniform and flat surface profile. In this work, mixed solvent of 20 vol % 1,2-dichlorobenzene (oDCB) with cyclohexylbenzene (CHB) was used to dissolve green quantum dots (QDs) with CdSe@ZnS/ZnS core/shell structure. Then, by inkjet printing, a flat dotlike QDs film without the coffee ring was successfully obtained on polyetherimide (PEI)-modified ZnO layer, and the printed dots array exhibited great stability and repeatability. Here, adding oDCB into CHB solutions was used to reduce surface tension, and employing ZnO nanoparticle layer with PEI-modified was used to increase the surface free energy. As a result, a small contact angle is formed, which leads to the enhancement of evaporation rate, and then the coffee ring effect was suppressed. The printed dots with flat surface profile were eventually realized. Moreover, inverted green QD-LEDs with PEI-modified ZnO film as electron transport layer (ETL) and printed green QDs film as emission layer were successfully fabricated. The QD-LEDs exhibited the maximum luminance of 12 000 cd/m 2 and the peak current efficiency of 4.5 cd/A at luminance of 1500 cd/m 2 .

Enhanced EJ Cell Killing of (125)I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter.

PubMed

Li, Ling; Zhang, Chun-li; Kang, Lei; Wang, Rong-Fu; Yan, Ping; Zhao, Qian; Yin, Lei; Guo, Feng-qin

2015-10-01

To investigate the enhancing effect of radionuclide therapy by the therapeutic gene placed under the control of radio-responsive promoter. The recombinant lentivirus E8-codA-GFP, including a synthetic radiation-sensitive promoter E8, cytosine deaminase (CD) gene, and green fluorescent protein gene, was constructed. The gene expression activated by (125)I radiation was assessed by observation of green fluorescence. The ability of converting 5-fluorocytosine (5-FC) to 5-fluorourial (5-FU) by CD enzyme was assessed by high-performance liquid chromatography. The viability of the infected cells exposed to (125)I in the presence of 5-FC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the infected cells exposed to (125)I alone served as negative control and 5-FU as positive control. The recombinant lentiviral vector was constructed successfully. On exposure of infected cells to (125)I, green fluorescence can be observed and 5-FU can be detected. MTT assay showed that the survival rate for infected cells treated with (125)I was lower compared with the (125)I control group, but higher than the positive control group. The synthetic promoter E8 can induce the expression of downstream CD gene under (125)I radiation, and the tumor killing effect of (125)I can be enhanced by combining CD gene therapy with radiosensitive promoter.

Chemical composition of some seaweed from Mediterranean Sea coast, Egypt.

PubMed

El-Said, Ghada F; El-Sikaily, Amany

2013-07-01

This study pointed to the assessment of the chemical composition (F, Ca, Mg, Na, K, Fe, Mn, Zn, Cu, Ni, Co, Cr, Cd, and carbohydrate) of different marine seaweeds (red, green, and brown) from the Egyptian Mediterranean Sea coast. The results showed that green seaweeds supplied better calcium sources than the red and brown ones. Also, red and brown seaweeds showed higher averages of Na and K than that in green species and these seaweeds could play an important role in the electrolyte balance in humans. On the other hand, green seaweeds gave the highest average carbohydrate concentration; thus, these green species could be used as a source of polysaccharides. Ion quotient values for almost seaweed species were between 1.4 and 4.0, so they can reduce hypertension, preeclampsia, and heart disease in human beings. Interestingly, the calculated hazard quotient of elements was below 1. Accordingly, these seaweed species were of high quality and safety and might be used in the field of nutrition.

Enforced IL-10 Expression Confers Type 1 Regulatory T Cell (Tr1) Phenotype and Function to Human CD4+ T Cells

PubMed Central

Andolfi, Grazia; Fousteri, Georgia; Rossetti, Maura; Magnani, Chiara F; Jofra, Tatiana; Locafaro, Grazia; Bondanza, Attilio; Gregori, Silvia; Roncarolo, Maria-Grazia

2012-01-01

Type 1 regulatory T (Tr1) cells are an inducible subset of CD4+ Tr cells characterized by high levels of interleukin (IL)-10 production and regulatory properties. Several protocols to generate human Tr1 cells have been developed in vitro. However, the resulting population includes a significant fraction of contaminating non-Tr1 cells, representing a major bottleneck for clinical application of Tr1 cell therapy. We generated an homogeneous IL-10–producing Tr1 cell population by transducing human CD4+ T cells with a bidirectional lentiviral vector (LV) encoding for human IL-10 and the marker gene, green fluorescent protein (GFP), which are independently coexpressed. The resulting GFP+ LV-IL-10–transduced human CD4+ T (CD4LV-IL-10) cells expressed, upon T-cell receptor (TCR) activation, high levels of IL-10 and concomitant low levels of IL-4, and markers associated with IL-10. Moreover, CD4LV-IL-10 T cells displayed typical Tr1 features: the anergic phenotype, the IL-10, and transforming growth factor (TGF)-β dependent suppression of allogeneic T-cell responses, and the ability to suppress in a cell-to-cell contact independent manner in vitro. CD4LV-IL-10 T cells were able to control xeno graft-versus-host disease (GvHD), demonstrating their suppressive function in vivo. These results show that constitutive over-expression of IL-10 in human CD4+ T cells leads to a stable cell population that recapitulates the phenotype and function of Tr1 cells. PMID:22692497

"In situ" observation of the role of chloride ion binding to monkey green sensitive visual pigment by ATR-FTIR spectroscopy.

PubMed

Katayama, Kota; Furutani, Yuji; Iwaki, Masayo; Fukuda, Tetsuya; Imai, Hiroo; Kandori, Hideki

2018-01-31

Long-wavelength-sensitive (LWS) pigment possesses a chloride binding site in its protein moiety. The binding of chloride alters the absorption spectra of LWS; this is known as the chloride effect. Although the two amino acid substitutions of His197 and Lys200 influence the chloride effect, the molecular mechanism of chloride binding, which underlies the spectral tuning, has yet to be clarified. In this study, we applied ATR-FTIR spectroscopy to monkey green (MG) pigment to gain structural information of the chloride binding site. The results suggest that chloride binding stabilizes the β-sheet structure on the extracellular side loop with perturbation of the retinal polyene chain, promotes a hydrogen bonding exchange with the hydroxyl group of Tyr, and alters the protonation state of carboxylate. Combining with the results of the binding analyses of various anions (Br - , I - and NO 3 - ), our findings suggest that the anion binding pocket is organized for only Cl - (or Br - ) to stabilize conformation around the retinal chromophore, which is functionally relevant with absorbing long wavelength light.

Differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause.

PubMed

Sophonsritsuk, Areepan; Appt, Susan E; Clarkson, Thomas B; Shively, Carol A; Espeland, Mark A; Register, Thomas C

2013-05-01

The aim of this study was to determine the effects of estrogen therapy (ET) on carotid artery inflammation when initiated early and late relative to surgical menopause. Female cynomolgus macaques consuming atherogenic diets were ovariectomized and randomized to control or oral estradiol (E2; human equivalent dose of 1 mg/d micronized E2) initiated at 1 month (early menopause, n = 24) or 54 months (late menopause, n = 40) after ovariectomy. The treatment period was 8 months. Carotid artery expression of the markers of monocyte/macrophages (CD68 and CD163), dendritic cells (CD83), natural killer cells (neural cell adhesion molecule-1), and interferon-γ was significantly lower in E2-treated animals in the early menopause group but not in the late menopause group (P < 0.05). In contrast, carotid artery transcripts for T-cell markers (CD3, CD4, CD8, and CD25), interleukin-10, type I collagen, monocyte chemoattractant protein-1, matrix metalloproteinase-9, and tumor necrosis factor-α were lower in E2-treated monkeys regardless of menopausal stage (P < 0.05). ET initiated soon after menopause inhibits macrophage accumulation in the carotid artery, an effect that is not observed when E2 is administered after several years of estrogen deficiency. No evidence for pro-inflammatory effects of late ET is observed. The results provide support for the timing hypothesis of postmenopausal ET with implications for the interpretation of outcomes in the Women's Health Initiative.

Production of Reference Enteroviruses

PubMed Central

Kalter, S. S.; Rodriguez, A. R.; Armour, V.

1968-01-01

Forty-five human enterovirus reagents of certified purity and quality were prepared for use as seed viruses and as immunizing antigens. One of the reagents was ampouled as “untreated” seed virus, whereas 14 were ampouled as “MgCl2-stabilized” reagents. The remaining 30 reagents were ampouled as “untreated” seed viruses and as “MgCl2-stabilized” reagents. Thirty of the reagents were propagated on primary African green monkey kidney cells, 3 on primary baboon kidney cells, 3 on primary rhesus monkey kidney cells, and the remaining 9 on human amnion cells. Forty-two of the viral antigens were concentrated for use in the production of high-titered specific antisera in large animals. PMID:4300898

Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obmolova, Galina; Teplyakov, Alexey; Malia, Thomas J.

CD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-κB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent. To identify the epitopes, we determined the crystal structure of the ternary complex between CD27 and the Fab fragments of these non-competing antibodies. The structuremore » reveals the binding modes of the antibodies suggesting that their mechanisms of action are distinctly different and provides a possible explanation of the in vivo data.« less

A field study to evaluate runoff quality from green roofs.

PubMed

Vijayaraghavan, K; Joshi, U M; Balasubramanian, R

2012-03-15

Green (vegetated) roofs are emerging as practical strategies to improve the environmental quality of cities. However, the impact of green roofs on the storm water quality remains a topic of concern to city planners and environmental policy makers. This study investigated whether green roofs act as a source or a sink of various metals (Na, K, Ca, Mg, Al, Fe, Cu, Cd, Pb, Zn, Mn, Cr, Ni, Li and Co), inorganic anions (NO3-, NO2-, PO4(3-), SO4(2-), Cl-, F- and Br-) and cation (NH4+). A series of green roof assemblies were constructed. Four different real rain events and several artificial rain events were considered for the study. Results showed that concentrations of most of the chemical components in runoff were highest during the beginning of rain events and subsided in the subsequent rain events. Some of the important components present in the runoff include Na, K, Ca, Mg, Li, Fe, Al, Cu, NO3-, PO4(3-) and SO4(2-). However, the concentration of these chemical components in the roof runoff strongly depends on the nature of substrates used in the green roof and the volume of rain. Based on the USEPA standards for freshwater quality, we conclude that the green roof used in this study is reasonably effective except that the runoff contains significant amounts of NO3- and PO4(3-). Copyright © 2011 Elsevier Ltd. All rights reserved.

Efficient triplet harvesting of hybrid white organic light-emitting diodes using thermally activated delayed fluorescence green emitter

NASA Astrophysics Data System (ADS)

Lee, Song Eun; Lee, Ho Won; Baek, Hyun Jung; Yun, Tae Jun; Yun, Geum Jae; Kim, Woo Young; Kim, Young Kwan

2016-10-01

Hybrid white organic light-emitting diodes (WOLEDs) were fabricated by applying triplet harvesting (TH) using a green thermally activated delayed fluorescence (TADF) emitter. The triplet exciton of the green TADF emitter can be upconverted to its singlet state. The TH involved energy transfer of triplet exciton from a blue fluorescent emitter to a green TADF and red phosphorescent emitters, where they can decay radiatively. In addition, the triplet exciton of the green TADF emitter was energy transferred to its singlet state for a reverse intersystem crossing by green emission. Enhanced hybrid WOLEDs were demonstrated using an efficient green TADF emitter combined with red phosphorescent and blue fluorescent emitters. Hybrid WOLEDs were fabricated with various hole-electron recombination zones as changing blue emitting layer thicknesses. Among these, hybrid WOLEDs showed a maximum external quantum efficiency of 11.23%, luminous efficiency of 29.20 cd/A, and a power efficiency of 26.21 lm/W. Moreover, the WOLED exhibited electroluminescence spectra with Commission International de L'Éclairage chromaticity of (0.38, 0.36) at 1000 cd/m2 and a color rendering index of 82 at a practical brightness of 20,000 cd/m2.

Primary simian immunodeficiency virus SIVmnd-2 infection in mandrills (Mandrillus sphinx).

PubMed

Onanga, Richard; Souquière, Sandrine; Makuwa, Maria; Mouinga-Ondeme, Augustin; Simon, François; Apetrei, Cristian; Roques, Pierre

2006-04-01

Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10(7) to 10(8) RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10(5) to 10(6) RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10(5) to 10(6) DNA copies/10(6) cells) and stabilized at 10(3) to 10(4) DNA copies/10(6) cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

The effect of age on the discriminative stimulus effects of ethanol and its GABA(A) receptor mediation in cynomolgus monkeys.

PubMed

Helms, Christa M; Grant, Kathleen A

2011-08-01

Excessive alcohol consumption is less common among aged compared to young adults, with aged adults showing greater sensitivity to many behavioral effects of ethanol. This study compared the discriminative stimulus effects of ethanol in young and middle-aged adult cynomolgus monkeys (Macaca fascicularis) and its γ-aminobutyric acid (GABA)(A) receptor mediation. Two male and two female monkeys trained to discriminate ethanol (1.0 g/kg, i.g.; 60-min pre-treatment interval) from water at 5-6 years of age (Grant et al. in Psychopharmacology 152:181-188, 2000) were re-trained in the current study more than a decade later (19.3 ± 1.0 years of age) for a within-subjects comparison. Also, four experimentally naïve middle-aged (mean ± SEM, 17.0 ± 1.5 years of age) female monkeys were trained to discriminate ethanol for between-subjects comparison with published data from young adult naïve monkeys. Two of the naïve middle-aged monkeys attained criterion performance, with weak stimulus control and few discrimination tests, despite greater blood-ethanol concentration 60 min after 1.0 g/kg ethanol in middle-aged compared to young adult female monkeys (Green et al. in Alcohol Clin Exp Res 23:611-616, 1999). The efficacy of the GABA(A) receptor positive modulators pentobarbital, midazolam, allopregnanolone, pregnanolone, and androsterone to substitute for the discriminative stimulus effects of 1.0 g/kg ethanol was maintained from young adulthood to middle age. The data suggest that 1.0 g/kg ethanol is a weak discriminative stimulus in naive middle-aged monkeys. Nevertheless, the GABA(A) receptor mechanisms mediating the discriminative stimulus effects of ethanol, when learned as a young adult, appear stable across one third of the primate lifespan.

Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy

PubMed Central

Byrareddy, Siddappa N.; Arthos, James; Cicala, Claudia; Villinger, Francois; Ortiz, Kristina T.; Little, Dawn; Sidell, Neil; Kane, Maureen A.; Yu, Jianshi; Jones, Jace W.; Santangelo, Philip J.; Zurla, Chiara; McKinnon, Lyle R.; Arnold, Kelly B.; Woody, Caroline E.; Walter, Lutz; Roos, Christian; Noll, Angela; Van Ryk, Donald; Jelicic, Katija; Cimbro, Raffaello; Gumber, Sanjeev; Reid, Michelle D.; Adsay, Volkan; Amancha, Praveen K.; Mayne, Ann E.; Parslow, Tristram G.; Fauci, Anthony S.; Ansari, Aftab A.

2017-01-01

Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α4β7 integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4+ T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn. This combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy. PMID:27738167

Photoluminescence and structural characteristics of CdS nanoclusters synthesized by hydrothermal microemulsion

NASA Astrophysics Data System (ADS)

Liu, Bing; Xu, G. Q.; Gan, L. M.; Chew, C. H.; Li, W. S.; Shen, Z. X.

2001-01-01

Spherical and uniform CdS nanoclusters were synthesized by hydrothermal microemulsion. The reaction of Cd2+ ions with S2- ions generated from the decomposition of thioacetamide proceeded in water microdroplets. The mean diameter of the CdS nanoclusters can be varied from 20 to 80 nm by increasing the reaction temperature from 30 to 120 °C. XRD results indicate that the resulting CdS nanoclusters have a reduced and distorted hexagonal lattice compared to bulk materials. Two intense luminescence bands, i.e., green and red, were observed to coexist in the CdS nanoclusters. Their peak positions and relative intensities were found to be sensitive to the size and structure of nanoclusters. These emissions are attributed to surface defects (green emission) and the Cd-Cl composite vacancies (red emission).

CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs for protection after ischemic stroke in mice.

PubMed

Wang, Jianping; Liu, Xi; Lu, Hong; Jiang, Chao; Cui, Xiaobing; Yu, Lie; Fu, Xiaojie; Li, Qian; Wang, Jian

2015-03-01

Cell-based therapy is considered to be a promising therapeutic strategy for stroke treatment. Although unfractionated bone marrow mononuclear cells (BMMNCs) have been tried in both preclinical and clinical trials, the effective subpopulations need to be identified. In this study, we used fluorescence-activated cell sorting to harvest the CXCR4(+)CD45(+) and CXCR4(+)CD45(-) BMMNC subpopulations from transgenic mice that express enhanced green fluorescent protein. We then allogeneically grafted unfractionated BMMNCs or a subpopulation into mice subjected to transient middle cerebral artery occlusion (tMCAO) and compared the effects on stroke outcomes. We found that CXCR4(+)CD45(-) BMMNCs, but not CXCR4(+)CD45(+) BMMNCs, more effectively reduced infarction volume and neurologic deficits than did unfractionated BMMNCs. Brain tissue from the ischemic hemisphere of mice treated with CXCR4(+)CD45(-) BMMNCs had higher levels of vascular endothelial growth factor and lower levels of TNF-α than did tissue from mice treated with unfractionated BMMNCs. In contrast, CXCR4(+)CD45(+) BMMNCs showed an increase in TNF-α. Additionally, CXCR4(+)CD45(+) and CXCR4(+)CD45(-) populations exhibited more robust migration into the lesion areas and were better able to express cell-specific markers of different linages than were the unfractionated BMMNCs. Endothelial and astrocyte cell markers did not colocalize with eGFP(+) cells in the brains of tMCAO mice that received CXCR4(+)CD45(+) BMMNCs. In vitro, the CXCR4(+)CD45(-) BMMNCs expressed significantly more Oct-4 and Nanog mRNA than did the unfractionated BMMNCs. However, we did not detect gene expression of these two pluripotent markers in CXCR4(+)CD45(+) BMMNCs. Taken together, our study shows for the first time that the CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs in ameliorating cerebral damage in a mouse model of tMCAO and could represent a new therapeutic approach for stroke treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Cation-Dependent Gold Recovery with α-Cyclodextrin Facilitated by Second-Sphere Coordination.

PubMed

Liu, Zhichang; Samanta, Avik; Lei, Juying; Sun, Junling; Wang, Yuping; Stoddart, J Fraser

2016-09-14

Herein, we report an alkali metal cation-dependent approach to gold recovery, facilitated by second-sphere coordination with eco-friendly α-cyclodextrin (α-CD). Upon mixing eight salts composed of Na(+), K(+), Rb(+), or Cs(+) cations and [AuX4](-) (X = Cl/Br) anions with α-, β-, or γ-CD in water, co-precipitates form selectively from the three (out of 24) aqueous solutions containing α-CD with KAuBr4, RbAuBr4, and CsAuBr4, from which the combination of α-CD and KAuBr4 affords the highest yield. Single-crystal X-ray analyses reveal that in 20 of the 24 adducts CD and [AuX4](-) anions form 2:1 sandwich-type second-sphere adducts driven partially by [C-H···X-Au] interactions between [AuX4](-) anions and the primary faces of two neighboring CDs. In the adduct formed between α-CD and KAuBr4, a [K(OH2)6](+) cation is encapsulated inside the cavity between the secondary faces of two α-CDs, leading to highly efficient precipitation owing to the formation of a cation/anion alternating ion wire residing inside a continuous α-CD nanotube. By contrast, in the other 19 adducts, the cations are coordinated by OH groups and glucopyranosyl ring O atoms in CDs. The strong coordination of Rb(+) and Cs(+) cations by these ligands, in conjunction with the stereoelectronically favorable binding of [AuBr4](-) anions with two α-CDs, facilitates the co-precipitation of the two adducts formed between α-CD with RbAuBr4 and CsAuBr4. In order to develop an efficient process for green gold recovery, the co-precipitation yield of α-CD and KAuBr4 has been optimized regarding both the temperature and the molar ratio of α-CD to KAuBr4.

Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

PubMed

Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

2016-09-01

Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recurrent Loss of APOBEC3H Activity during Primate Evolution.

PubMed

Garcia, Erin I; Emerman, Michael

2018-06-20

Genes in the APOBEC3 family encode cytidine deaminases that provide a barrier against viral infection and retrotransposition. Of all APOBEC3 genes in humans, APOBEC3H ( A3H ) is the most polymorphic: some haplotypes encode stable and active A3H proteins, while others are unstable and poorly antiviral. Such variation in human A3H affects interactions with the lentiviral antagonist Vif, which counteracts A3H via proteasomal degradation. In order to broaden our understanding of A3H-Vif interactions, as well as its evolution in Old World monkeys, we characterized A3H variation within four African green monkey (AGM) subspecies. We found that A3H is highly polymorphic in AGMs and has lost antiviral activity in multiple Old World monkeys. This loss of function was partially related to protein expression levels but was also influenced by amino acid mutations in the N-terminus. Moreover, we demonstrate that the evolution of A3H in the primate lineages leading to AGMs was not driven by Vif. Our work suggests that activity of A3H is evolutionarily dynamic and may have a negative effect on host fitness, resulting in its recurrent loss in primates. IMPORTANCE Adaptation of viruses to their hosts is critical for transmission of viruses between different species. Previous studies had identified changes in a protein from the APOBEC3 family that influenced species-specificity of simian immunodeficiency viruses (SIVs) in African green monkeys. We studied the evolution of a related protein in the same system, APOBEC3H, which has experienced a loss of function in humans. This evolutionary approach revealed that recurrent loss of APOBEC3H activity has taken place during primate evolution suggesting that APOBEC3H places a fitness cost on hosts. The variability of APOBEC3H activity between different primates highlights the differential selective pressures on the APOBEC3 gene family. Copyright © 2018 American Society for Microbiology.

Seeing Beyond the Monkey Head

NASA Image and Video Library

2015-08-20

Scores of baby stars shrouded by dust are revealed in this infrared image of the star-forming region NGC 2174, as seen by NASA Spitzer Space Telescope. Found in the constellation Orion, NGC 2174 is located around 6,400 light-years away. Some of the clouds in the region resemble the face of a monkey in visible-light images, hence the nebula's nickname: the "Monkey Head." However, in infrared images such as this, the monkey disappears. That's because different clouds are highlighted in infrared and visible-light images. Found in the northern reaches of the constellation Orion, NGC 2174 is located around 6,400 light-years away. Columns of dust, slightly to the right of center in the image, are being carved out of the dust by radiation and stellar winds from the hottest young stars recently born in the area. Spitzer's infrared view provides us with a preview of the next clusters of stars that will be born in the coming millennia. The reddish spots of light scattered through the darker filaments are infant stars swaddled by blankets of warm dust. The warm dust glows brightly at infrared wavelengths. Eventually, these stars will pop out of their dusty envelopes and their light will carve away at the dust clouds surrounding them. In this image, infrared wavelengths have been assigned visible colors we see with our eyes. Light with a wavelength of 3.5 microns is shown in blue, 8.0 microns is green, and 24 microns in red. The greens show the organic molecules in the dust clouds, illuminated by starlight. Reds are caused by the thermal radiation emitted from the very hottest areas of dust. Areas around the edges that were not observed by Spitzer have been filled in using infrared observations from NASA's Wide Field Infrared Survey Explorer, or WISE. http://photojournal.jpl.nasa.gov/catalog/PIA19836

A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

PubMed

Khachaturian, Mark Haig

2010-01-01

Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments

PubMed Central

Khachaturian, Mark Haig

2010-01-01

Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4–8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic). PMID:21243106

Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

PubMed

Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

2010-08-25

To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.

PubMed

Doss, Mohan; Zhang, James J; Bélanger, Marie-José; Stubbs, James B; Hostetler, Eric D; Alpaugh, Katherine; Kolb, Hartmuth C; Yu, Jian Q

2010-12-01

F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans. Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software. The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data. Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.

PubMed

Shimizudani, Takeshi; Nagaoka, Kenjiro; Hanioka, Nobumitsu; Yamano, Shigeru; Narimatsu, Shizuo

2010-01-05

Oxidative metabolism of propranolol (PL) enantiomers (R-PL and S-PL) to 4-hydroxypropranolol (4-OH-PL), 5-OH-PL and N-deisopropylpropranolol (NDP) was examined in hepatic microsomes from cynomolgus and marmoset monkeys and in small intestinal microsomes from monkeys and humans. In hepatic microsomes, levels of oxidation activities were similar between the two monkey species, and substrate enantioselectivity (R-PLS-PL) was seen in the formation of NDP in cynomolgus monkeys and humans and in the formation of 5-OH-PL in marmosets. The formation of the three metabolites in cynomolgus monkeys and the formation of NDP in marmosets were biphasic, while the formation of 4-OH-PL in humans was monophasic. From the inhibition experiments using CYP antibodies, CYP2C9 and 2C19 were thought to be involved as N-deisopropylases and CYP2D6 and 3A4 as 4-hydroxylases in human small intestine. Furthermore, CYP1A, 2C and 3A enzymes could be involved in cynomolgus monkeys and CYP2C and 3A enzymes in marmosets. These results indicate that the oxidative profile of PL in hepatic and small intestinal microsomes differ considerably among cynomolgus monkeys, marmosets and humans.

Microwave-assisted synthesis and anti-YFV activity of 2,3-diaryl-1,3-thiazolidin-4-ones.

PubMed

Sriram, Dharmarajan; Yogeeswari, Perumal; Kumar, T G Ashok

2005-09-01

The purpose of this study was to prepare several 1,3-thaizolidin-4-ones bearing variously substituted diaryl ring at C-2 and N-3 positions and evaluate them for their anti-YFV activity. Several 1,3-thaizolidin-4-ones were prepared by reacting substituted benzaldehyde with equimolar amount of an appropriate substituted aromatic amine in the presence of an excess of mercaptoacetic acid in toluene utilizing microwave irradiation. The synthesized compounds were also evaluated for their inhibitory effects on the replication of YFV in green monkey kidney (Vero) cells (ATCC CCL81), by means of a cytopathic effect reduction assay. The compound DS1 emerged as the most potent anti-YFV agent with EC50 of 6.9 microM and CC50 more than 100 microM making it more potent than ribavirin. 2,3-diaryl-1,3-thiazolidin-4-ones possess anti-YFV potency.

Water Quality Criteria for Colored Smokes: Solvent Green 3

DTIC Science & Technology

1987-12-01

by the oral, dermal, or inhalation route. The acute oral LD50 is >3.16 g/kg in rats, but may be as high as 15 g/kg, >1 g/kg in dogs , and 10 g/kg in...0 is >3.16 g/kg, but may be as high as 15 g/kg in rats, >1 g/kg in dogs , and 10 g/kg in rabbits. Solvent Green 3 is not irritating to eyes and is...only mildly irritating to the skin. The acute LCt 5 0 for five experimental animal species combined (monkeys, dogs , swine, rabbits, and rats) is 319,447

Sucrose acetate isobutyrate (SAIB): historical aspects of its use in beverages and a review of toxicity studies prior to 1988.

PubMed

Reynolds, R C; Chappel, C I

1998-02-01

Sucrose acetate isobutyrate (SAIB), a mixture of esters of sucrose with a composition approximating the name sucrose diacetate hexaisobutyrate, has been used for over 30 yr in many countries as a 'weighting' or 'density-adjusting' agent in non-alcoholic carbonated and non-carbonated beverages. As part of the demonstration of safety of SAIB as a direct food additive in human diets, a program of toxicity testing was started in the late 1950s that culminated in extensive studies of SAIB in rodents, monkeys and humans over the last decade. This review summarizes the toxicity data, accrued up until 1988, that precede the safety studies published elsewhere in this issue. SAIB has been shown to have very low acute and chronic toxicities in rats, monkeys, and, except for effects on the liver, in dogs at feeding levels of up to 10% in the diet. Slight effects seen in rats and monkeys at levels of 10% in the diet are unlikely to be directly caused by exposure to SAIB. In dogs, however, SAIB causes decreases in bromosulfophthalein (BSP) and indocyanine green (ICG) elimination from the serum immediately following a single dose, indicative of interference with biliary excretion. On repeated feeding in dogs, SAIB caused increases in serum alkaline phosphatase levels, but enzymes indicative of toxic effects on the liver were unaffected. On prolonged feeding to dogs, SAIB caused changes in liver morphology revealed by electron microscopy. All of these effects were reversed when SAIB was withdrawn from the diet. The no-effect level for these effects in dogs was near 5 mg/kg body weight, but these effects were not seen in rats fed up to 4 g/kg body weight/day, monkeys fed up to 10 g/kg body weight/day, or humans fed up to 20 mg/kg body weight/day. The toxicity and pharmacological studies in dogs, rats and monkeys suggest that the effect of SAIB on biliary excretion and liver morphology in dogs is essentially pharmacological rather than toxicological in nature and that the difference between the effects in dogs at levels as low as 5 mg/kg body weight/day, and the lack of effects in rats or monkeys at levels up to 10 g/kg/day is not merely a quantitative difference between species, but an absolute qualitative difference.

Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide.

PubMed

Frazier, Kendall S; Sobry, Cécile; Derr, Victoria; Adams, Mike J; Besten, Cathaline Den; De Kimpe, Sjef; Francis, Ian; Gales, Tracy L; Haworth, Richard; Maguire, Shaun R; Mirabile, Rosanna C; Mullins, David; Palate, Bernard; Doorten, Yolanda Ponstein-Simarro; Ridings, James E; Scicchitano, Marshall S; Silvano, Jérémy; Woodfine, Jennie

2014-07-01

Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration. Glomerulopathy occurred in both species with species-specific characteristics. Glomerular lesions in mice were characterized by progressive hyaline matrix accumulation, accompanied by the presence of renal amyloid and with subsequent papillary necrosis. Early changes involved glomerular endothelial hypertrophy and degeneration, but the chronic glomerular amyloid and hyaline alterations in mice appeared to be species specific. An immune-mediated mechanism for the glomerular lesions in mice was supported by early inflammatory changes including increased expression of inflammatory cytokines and other immunomodulatory genes within the renal cortex, increased stimulation of CD68 protein, and systemic elevation of monocyte chemotactic protein 1. In contrast, kidneys from monkeys given drisapersen chronically showed less severe glomerular changes characterized by increased mesangial and inflammatory cells, endothelial cell hypertrophy, and subepithelial and membranous electron-dense deposits, with ultrastructural and immunohistochemical characteristics of complement and complement-related fragments. Lesions in monkeys resembled typical features of C3 glomerulopathy, a condition described in man and experimental animals to be linked to dysregulation of the alternative complement pathway. Thus, inflammatory/immune mechanisms appear critical to glomerular injury with species-specific sensitivities for mouse and monkey. The lower observed proinflammatory activity in humans as compared to mice and monkeys may reflect a lower risk of glomerular injury in patients receiving AON therapy. © 2014 by The Author(s).

Highly efficient single-layer dendrimer light-emitting diodes with balanced charge transport

NASA Astrophysics Data System (ADS)

Anthopoulos, Thomas D.; Markham, Jonathan P. J.; Namdas, Ebinazar B.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.

2003-06-01

High-efficiency single-layer-solution-processed green light-emitting diodes based on a phosphorescent dendrimer are demonstrated. A peak external quantum efficiency of 10.4% (35 cd/A) was measured for a first generation fac-tris(2-phenylpyridine) iridium cored dendrimer when blended with 4,4'-bis(N-carbazolyl)biphenyl and electron transporting 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene at 8.1 V. A maximum power efficiency of 12.8 lm/W was measured also at 8.1 V and 550 cd/m2. These results indicate that, by simple blending of bipolar and electron-transporting molecules, highly efficient light-emitting diodes can be made employing a very simple device structure.

DRD4 dopamine receptor allelic diversity in various primate species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, M.; Higley, D.; O`Brien, S.

The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypesmore » in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.« less

Movement of retinal vessels toward the optic nerve head after increasing intraocular pressure in monkey eyes with experimental glaucoma.

PubMed

Kuroda, Atsumi; Enomoto, Nobuko; Ishida, Kyoko; Shimazawa, Masamitsu; Noguchi, Tetsuro; Horai, Naoto; Onoe, Hirotaka; Hara, Hideaki; Tomita, Goji

2017-09-01

A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim thinning indicates the progression of glaucomatous optic neuropathy. In chronic open angle glaucoma, individuals with RBV positional shifts exhibit more rapid visual field loss than those without RBV shifts. The retinal vessels reportedly move onto the optic nerve head (ONH) in response to glaucoma damage, suggesting that RBVs are pulled toward the ONH in response to increased cupping. Whether this phenomenon only applies to RVBs located in the vicinity or inside the ONH or, more generally, to RBVs also located far from the ONH, however, is unclear. The aim of this study was to evaluate the movement of RBVs located relatively far from the ONH edge after increasing intraocular pressure (IOP) in an experimental monkey model of glaucoma. Fundus photographs were obtained in 17 monkeys. High IOP was induced in the monkeys by laser photocoagulation burns applied uniformly with 360° irradiation around the trabecular meshwork of the left eye. The right eye was left intact and used as a non-treated control. Considering the circadian rhythm of IOP, it was measured in both eyes of each animal at around the same time-points. Then, fundus photographs were obtained. Using Image J image analysis software, an examiner (N.E.) measured the fundus photographs at two time-points, i.e. before laser treatment (time 1) and the last fundus photography after IOP elevation (time 2). The following parameters were measured (in pixels): 1) vertical diameter of the ONH (DD), 2) distance from the ONH edge to the first bifurcation point of the superior branch of the central retinal vein (UV), 3) distance from the ONH edge to the first bifurcation point of the inferior branch of the central retinal vein (LV), 4) ONH area, and 5) surface area of the cup of the ONH. We calculated the ratios of UV to DD (UV/DD), LV to DD (LV/DD), and the cup area to disc area ratio (C/D). The mean UV/DD at time 1 (0.656 ± 0.233) was decreased at time 2 (0.542 ± 0.192) (p < 0.01), and the mean LV/DD at time 1 (0.642 ± 0.151) was decreased at time 2 (0.534 ± 0.171) (p < 0.01). The mean C/D at time 1 (0.303 ± 0.035) was increased at time 2 (0.556 ± 0.110) (p < 0.01). The mean IOP at time 1 was 19.8 ± 2.5 and that at time 2 was 54.2 ± 15.8. The amount and rate of the change in LV/DD and C/D between time 1 and time 2 were significantly correlated (r = -0.654 and -0.536, p = 0.004 and 0.026, respectively). Therefore, in an experimental monkey model of glaucoma, RBVs located relatively far from the ONH were pulled toward the ONH as cupping increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jung-Bum; Lee, Jeong-Hwan; Moon, Chang-Ki

We report a highly efficient phosphorescent green inverted top emitting organic light emitting diode with excellent color stability by using the 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile/indium zinc oxide top electrode and bis(2-phenylpyridine)iridium(III) acetylacetonate as the emitter in an exciplex forming co-host system. The device shows a high external quantum efficiency of 23.4% at 1000 cd/m{sup 2} corresponding to a current efficiency of 110 cd/A, low efficiency roll-off with 21% at 10 000 cd/m{sup 2} and low turn on voltage of 2.4 V. Especially, the device showed very small color change with the variation of Δx = 0.02, Δy = 0.02 in the CIE 1931 coordinates as the viewing angle changes from 0° tomore » 60°. The performance of the device is superior to that of the metal/metal cavity structured device.« less

Spaceflight and immune responses of rhesus monkeys

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

1995-01-01

The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

V1 mechanisms underlying chromatic contrast detection

PubMed Central

Hass, Charles A.

2013-01-01

To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

One-step, low-temperature fabrication of CdS quantum dots by watermelon rind: a green approach

PubMed Central

Lakshmipathy, Rajasekhar; Sarada, Nallani Chakravarthula; Chidambaram, K; Pasha, Sk Khadeer

2015-01-01

We investigated the one-step synthesis of CdS nanoparticles via green synthesis that used aqueous extract of watermelon rind as a capping and stabilizing agent. Preliminary phytochemical analysis depicted the presence of carbohydrates which can act as capping and stabilizing agents. Synthesized CdS nanoparticles were characterized using UV-visible, Fourier transform infrared spectroscopy, X-ray diffraction, EDX, dynamic light scattering, transmission electron microscopy, and atomic force microscopy techniques. The CdS nanoparticles were found to be size- and shape-controlled and were stable even after 3 months of synthesis. The results suggest that watermelon rind, an agro-waste, can be used for synthesis of CdS nanoparticles without any addition of stabilizing and capping agents. PMID:26491319

Nuclear-mitochondrial incompatibility in interorder rhesus monkey-cow embryos derived from somatic cell nuclear transfer.

PubMed

Kwon, Daekee; Koo, Ok-Jae; Kim, Min-Jung; Jang, Goo; Lee, Byeong Chun

2016-10-01

Monkey interorder somatic cell nuclear transfer (iSCNT) using enucleated cow oocytes yielded poor blastocysts development and contradictory results among research groups. Determining the reason for this low blastocyst development is a prerequisite for optimizing iSCNT in rhesus monkeys. The aim of this study was to elucidate nuclear-mitochondrial incompatibility of rhesus monkey-cow iSCNT embryos and its relationship to low blastocyst development. Cytochrome b is a protein of complex III of the electron transport chain (ETC). According to meta-analysis of amino acid sequences, the homology of cytochrome b is 75 % between rhesus monkeys and cattle. To maintain the function of ETC after iSCNT, 4n iSCNT embryos were produced by fusion of non-enucleated cow oocytes and rhesus monkey somatic cells. The blastocyst development rate of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Formation of reactive oxygen species (ROS) is an indirect indicator of ETC activity of cells. The ROS levels of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Collectively, rhesus monkey iSCNT embryos reconstructed with cow oocytes have nuclear-mitochondrial incompatibility due to fundamental species differences between rhesus monkeys and cattle. Nuclear-mitochondrial incompatibility seems to correlate with low ETC activity and extremely low blastocyst development of rhesus monkey-cow iSCNT embryos.

Synthesis, characterisation and catalytic activity of 4, 5-imidazoledicarboxylate ligated Co(II) and Cd(II) metal-organic coordination complexes

NASA Astrophysics Data System (ADS)

Gangu, Kranthi Kumar; Maddila, Suresh; Mukkamala, Saratchandra Babu; Jonnalagadda, Sreekantha B.

2017-09-01

Two mono nuclear coordination complexes, namely, [Co(4,5-Imdc)2 (H2O)2] (1) and [Cd(4,5-Imdc)2(H2O)3]·H2O (2) were constructed using Co(II) and Cd(II) metal salts with 4,5-Imidazoledicarboxylic acid (4,5-Imdc) as organic ligand. Both 1, 2 were structurally characterized by single crystal XRD and the results reveal that 1 belongs to P21/n space group with unit cell parameters [a = 5.0514(3) Å, b = 22.5786(9) Å, c = 6.5377(3) Å, β = 111.5°] whereas, 2 belongs to P21/c space group with unit cell parameters [a = 6.9116(1) Å, b = 17.4579(2) Å, c = 13.8941(2) Å, β = 97.7°]. While Co(II) in 1 exhibited a six coordination geometry with 4,5-Imdc and water molecules, Cd(II) ion in 2 showed a seven coordination with the same ligand and solvent. In both 1 and 2, the hydrogen bond interactions with mononuclear unit generated 3D-supramolecular structures. Both complexes exhibit solid state fluorescent emission at room temperature. The efficacy of both the complexes as heterogeneous catalysts was examined in the green synthesis of six pyrano[2,3,c]pyrazole derivatives with ethanol as solvent via one-pot reaction between four components, a mixture of aromatic aldehyde, malononitrile, hydrazine hydrate and dimethyl acetylenedicarboxylate. Both 1 and 2 have produced pyrano [2,3,c]pyrazoles in impressive yields (92-98%) at room temperature in short interval of times (<20 min), with no need for any chromatographic separations. With good stability, ease of preparation and recovery plus reusability up to six cycles, both 1 and 2 prove to be excellent environmental friendly catalysts for the value-added organic transformations using green principles.

Algae mediated synthesis of cadmium sulphide nanoparticles and their application in bioremediation

NASA Astrophysics Data System (ADS)

Prasad Mandal, Ranju; Sekh, Sanoyaz; Sarkar, Neera Sen; Chattopadhyay, Dipankar; De, Swati

2016-05-01

The present work is a study on the biological synthesis of cadmium sulphide (CdS) nanoparticles using blue-green algae that is popularly used as a food supplement. This synthesis is unique in the sense that no external sulphur precursor is required, the CdS nanoparticles are synthesized in situ in the algal medium. The CdS nanoparticles thus synthesized are photoluminescent and can act as highly efficient photocatalysts for degradation of the dye pollutant malachite green. Thus the CdS nanoparticles synthesized in situ in the algae conform to the desired criteria of waste water treatment i.e. biosorption of the pollutant and its subsequent degradation. The novelty of this work also lies in its potential for use in bioremediation by conversion of the toxic Cd(II) ion to less toxic CdS nanoparticles within the algal framework.

A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections.

PubMed

Li, Hao; Lei, Xiaoguang; Huang, Baihui; Rizak, Joshua D; Yang, Lichuan; Yang, Shangchuan; Wu, Jing; Lü, Longbao; Wang, Jianhong; Yan, Ting; Li, Hongwei; Wang, Zhengbo; Hu, Yingzhou; Le, Weidong; Deng, Xingli; Li, Jiali; Xu, Lin; Zhang, Baorong; Hu, Xintian

2015-08-15

Non-human primate Parkinson's disease (PD) models are essential for PD research. The most extensively used PD monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the modeling processes of developing PD monkeys cannot be quantitatively controlled with MPTP. Therefore, a new approach to quantitatively develop chronic PD monkey models will help to advance the goals of "reduction, replacement and refinement" in animal experiments. A novel chronic PD monkey models was reported using the intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP(+)) in Cynomolgus monkeys (Macaca fascicularis). This approach successfully produced stable and consistent PD monkeys with typical motor symptoms and pathological changes. More importantly, a sigmoidal relationship (Y=8.15801e(-0.245/x); R=0.73) was discovered between PD score (Y) and cumulative dose of MPP(+) (X). This relationship was then used to develop two additional PD monkeys under a specific time schedule (4 weeks), with planned PD scores (7) by controlling the dose and frequency of the MPP(+) administration as an independent validation of the formula. We developed Parkinsonian monkeys within controlled time frames by regulating the accumulated dose of MPP(+) intracerebroventricular administered, while limiting side effects often witnessed in models developed with the peripheral administration of MPTP, makes this model highly suitable for treatment development. This novel approach provides an edge in evaluating the mechanisms of PD pathology associated with environmental toxins and novel treatment approaches as the formula developed provides a "map" to control and predict the modeling processes. Copyright © 2015 Elsevier B.V. All rights reserved.

High Expression of UGT1A1/1A6 in Monkey Small Intestine: Comparison of Protein Expression Levels of Cytochromes P450, UDP-Glucuronosyltransferases, and Transporters in Small Intestine of Cynomolgus Monkey and Human.

PubMed

Akazawa, Takanori; Uchida, Yasuo; Miyauchi, Eisuke; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

2018-01-02

Cynomolgus monkeys have been widely used for the prediction of drug absorption in humans. The purpose of this study was to clarify the regional protein expression levels of cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UGTs), and transporters in small intestine of cynomolgus monkey using liquid chromatography-tandem mass spectrometry, and to compare them with the corresponding levels in human. UGT1A1 in jejunum and ileum were >4.57- and >3.11-fold and UGT1A6 in jejunum and ileum were >16.1- and >8.57-fold, respectively, more highly expressed in monkey than in human. Also, jejunal expression of monkey CYP3A8 (homologue of human CYP3A4) was >3.34-fold higher than that of human CYP3A4. Among apical drug efflux transporters, BCRP showed the most abundant expression in monkey and human, and the expression levels of BCRP in monkey and human were >1.74- and >1.25-fold greater than those of P-gp and >2.76- and >4.50-fold greater than those of MRP2, respectively. These findings should be helpful to understand species differences of the functions of CYPs, UGTs, and transporters between monkey and human. The UGT1A1/1A6 data would be especially important because it is difficult to identify isoforms responsible for species differences of intestinal glucuronidation by means of functional studies due to overlapping substrate specificity.

Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

DTIC Science & Technology

2014-12-01

and the dome connected to tension transducers. Preparations were stretched to optimal resting tension ( Lo ) and allowed to equilibrate for 30 min...B SCT (200x) Uro LumenA Red: P2Y6 Green: vimentin Blue: DAPI Figure 11 13 This suggests there are different populations of IC within the bladder...Lumen Uro Control (200x) SCT (600x) Green: CD34 Blue: DAPI Red: P2Y6 Green: CD34 Blue: DAPI Figure 12 14 It was the first animal model

HAVCR1 (CD365) and Its Mouse Ortholog Are Functional Hepatitis A Virus (HAV) Cellular Receptors That Mediate HAV Infection.

PubMed

Costafreda, Maria Isabel; Kaplan, Gerardo

2018-05-01

The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), classified as CD365, was initially discovered as an HAV cellular receptor using an expression cloning strategy. Due to the lack of HAV receptor-negative replication-competent cells, it was not possible to fully prove that HAVCR1 was a functional HAV receptor. However, biochemistry, classical virology, and epidemiology studies further supported the functional role of HAVCR1 as an HAV receptor. Here, we show that an anti-HAVCR1 monoclonal antibody that protected African green monkey kidney (AGMK) cells against HAV infection only partially protected monkey Vero E6 cells and human hepatoma Huh7 cells, indicating that these two cell lines express alternative yet unidentified HAV receptors. Therefore, we focused our work on AGMK cells to further characterize the function of HAVCR1 as an HAV receptor. Advances in clustered regularly interspaced short palindromic repeat/Cas9 technology allowed us to knock out the monkey ortholog of HAVCR1 in AGMK cells. The resulting AGMK HAVCR1 knockout (KO) cells lost susceptibility to HAV infection, including HAV-free viral particles (vpHAV) and exosomes purified from HAV-infected cells (exo-HAV). Transfection of HAVCR1 cDNA into AGMK HAVCR1 KO cells restored susceptibility to vpHAV and exo-HAV infection. Furthermore, transfection of the mouse ortholog of HAVCR1, mHavcr1, also restored the susceptibility of AGMK HAVCR1 KO cells to HAV infection. Taken together, our data clearly show that HAVCR1 and mHavcr1 are functional HAV receptors that mediate HAV infection. This work paves the way for the identification of alternative HAV receptors to gain a complete understanding of their interplay with HAVCR1 in the cell entry and pathogenic processes of HAV. IMPORTANCE HAVCR1, an HAV receptor, is expressed in different cell types, including regulatory immune cells and antigen-presenting cells. How HAV evades the immune response during a long incubation period of up to 4 weeks and the mechanism by which the subsequent necroinflammatory process clears the infection remain a puzzle that most likely involves the HAV-HAVCR1 interaction. Based on negative data, a recent paper from the S. M. Lemon and W. Maury laboratories (A. Das, A. Hirai-Yuki, O. Gonzalez-Lopez, B. Rhein, S. Moller-Tank, R. Brouillette, L. Hensley, I. Misumi, W. Lovell, J. M. Cullen, J. K. Whitmire, W. Maury, and S. M. Lemon, mBio 8:e00969-17, 2017, https://doi.org/10.1128/mBio.00969-17) suggested that HAVCR1 is not a functional HAV receptor, nor it is it required for HAV infection. However, our data, based on regain of the HAV receptor function in HAVCR1 knockout cells transfected with HAVCR1 cDNA, disagree with their findings. Our positive data show conclusively that HAVCR1 is indeed a functional HAV receptor and lays the ground for the identification of alternative HAV receptors and how they interact with HAVCR1 in cell entry and the pathogenesis of HAV. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Baseline Serum Clinical Chemistry Values in African Green Monkeys Before and After Sulfur Mustard

DTIC Science & Technology

2007-05-01

aspartate transaminase (189 %), blood urea nitrogen (75 %), creatine kinase (721 %), and lactate dehydrogenase (114 %) one day after HD exposure...ALT, 93 %), aspartate transaminase (AST, 189 %), blood urea nitrogen (BUN, 75 %), creatine kinase (CK, 721 %), and lactate dehydrogenase (LDH, 114...alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), calcium (Ca2+), creatine kinase (CK

9 CFR 113.53 - Requirements for ingredients of animal origin used for production of biologics.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (African green monkey kidney) cell line and of primary cells or a cell line of the same species of origin... origin used for production of biologics. 113.53 Section 113.53 Animals and Animal Products ANIMAL AND... ingredients of animal origin used for production of biologics. Each lot of ingredient of animal origin which...

9 CFR 113.53 - Requirements for ingredients of animal origin used for production of biologics.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (African green monkey kidney) cell line and of primary cells or a cell line of the same species of origin... origin used for production of biologics. 113.53 Section 113.53 Animals and Animal Products ANIMAL AND... ingredients of animal origin used for production of biologics. Each lot of ingredient of animal origin which...

9 CFR 113.53 - Requirements for ingredients of animal origin used for production of biologics.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (African green monkey kidney) cell line and of primary cells or a cell line of the same species of origin... origin used for production of biologics. 113.53 Section 113.53 Animals and Animal Products ANIMAL AND... ingredients of animal origin used for production of biologics. Each lot of ingredient of animal origin which...

Single-dose live-attenuated vesicular stomatitis virus-based vaccine protects African green monkeys from Nipah virus disease.

PubMed

Prescott, Joseph; DeBuysscher, Blair L; Feldmann, Friederike; Gardner, Donald J; Haddock, Elaine; Martellaro, Cynthia; Scott, Dana; Feldmann, Heinz

2015-06-04

Nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. It is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in Bangladesh or India. Outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of Nipah virus disease. There are no approved countermeasures to combat infection and medical intervention is supportive. We recently generated a recombinant replication-competent vesicular stomatitis virus-based vaccine that encodes a Nipah virus glycoprotein as an antigen and is highly efficacious in the hamster model of Nipah virus disease. Herein, we show that this vaccine protects African green monkeys, a well-characterized model of Nipah virus disease, from disease one month after a single intramuscular administration of the vaccine. Vaccination resulted in a rapid and strong virus-specific immune response which inhibited virus shedding and replication. This vaccine platform provides a rapid means to afford protection from Nipah virus in an outbreak situation. Published by Elsevier Ltd.

Control of communicable disease; foreign--requirements for importers of nonhuman primates (NHP). Final rule.

PubMed

2013-02-15

The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), is amending regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs with the exception of the filovirus testing requirement. Filovirus testing will only be required for Old World NHPs in quarantine that have illness consistent with filovirus infection or that die for any reason other than trauma during quarantine. HHS/CDC is also finalizing a provision to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their special permits (from every 180 days to every 2 years). HHS/CDC is incorporating existing guidelines into the regulations and adding new provisions to address the following: NHPs imported as part of an animal act; NHPs imported or transferred by zoological societies; the transfer of NHPs from approved laboratories; and non-live imported NHP products. Finally, HHS/CDC is also requiring that all NHPs be imported only through ports of entry where a HHS/CDC quarantine station is located.

78 FR 11521 - Control of Communicable Disease; Foreign-Requirements for Importers of Nonhuman Primates (NHP)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

...The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), is amending regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs with the exception of the filovirus testing requirement. Filovirus testing will only be required for Old World NHPs in quarantine that have illness consistent with filovirus infection or that die for any reason other than trauma during quarantine. HHS/CDC is also finalizing a provision to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their special permits (from every 180 days to every 2 years). HHS/CDC is incorporating existing guidelines into the regulations and adding new provisions to address the following: NHPs imported as part of an animal act; NHPs imported or transferred by zoological societies; the transfer of NHPs from approved laboratories; and non-live imported NHP products. Finally, HHS/CDC is also requiring that all NHPs be imported only through ports of entry where a HHS/CDC quarantine station is located.

Single-dose Live-attenuated Vesicular Stomatitis Virus-based Vaccine Protects African Green Monkeys from Nipah Virus Disease

PubMed Central

Prescott, Joseph; DeBuysscher, Blair L.; Feldmann, Friederike; Gardner, Donald J.; Haddock, Elaine; Martellaro, Cynthia; Scott, Dana; Feldmann, Heinz

2015-01-01

Nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. It is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in Bangladesh or India. Outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of Nipah virus disease. There are no approved countermeasures to combat infection and medical intervention is supportive. We recently generated a recombinant replication-competent vesicular stomatitis virus-based vaccine that encodes a Nipah virus glycoprotein as an antigen and is highly efficacious in the hamster model of Nipah virus disease. Herein, we show that this vaccine protects African green monkeys, a well-characterized model of Nipah virus disease, from disease one month after a single intramuscular administration of the vaccine. Vaccination resulted in a rapid and strong virus-specific immune response which inhibited virus shedding and replication. This vaccine platform provides a rapid means to afford protection from Nipah virus in an outbreak situation. PMID:25865472

Failure of transplantation tolerance induction by autologous regulatory T cells in the pig-to-non-human primate islet xenotransplantation model.

PubMed

Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Jong-Min; Kim, Jung-Sik; Yoon, Il Hee; Kim, Hyun Je; Kim, Yong-Hee; Jang, Jae Yool; Kang, Hee Jung; Lim, Dong-Gyun; Ha, Jongwon; Kim, Sang-Joon; Park, Chung-Gyu

2016-07-01

Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University (SNU) miniature pigs with immunosuppression by anti-thymoglobulin (ATG), cobra venom factor, anti-CD154 monoclonal antibody (mAb), and sirolimus. CD4(+) CD25(high) CD127(low) autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40-CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40-CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to-NHP islet xenotransplantation setting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lentiviral Nef suppresses iron uptake in a strain specific manner through inhibition of Transferrin endocytosis

PubMed Central

2014-01-01

Background Increased cellular iron levels are associated with high mortality in HIV-1 infection. Moreover iron is an important cofactor for viral replication, raising the question whether highly divergent lentiviruses actively modulate iron homeostasis. Here, we evaluated the effect on cellular iron uptake upon expression of the accessory protein Nef from different lentiviral strains. Results Surface Transferrin receptor (TfR) levels are unaffected by Nef proteins of HIV-1 and its simian precursors but elevated in cells expressing Nefs from most other primate lentiviruses due to reduced TfR internalization. The SIV Nef-mediated reduction of TfR endocytosis is dependent on an N-terminal AP2 binding motif that is not required for downmodulation of CD4, CD28, CD3 or MHCI. Importantly, SIV Nef-induced inhibition of TfR endocytosis leads to the reduction of Transferrin uptake and intracellular iron concentration and is accompanied by attenuated lentiviral replication in macrophages. Conclusion Inhibition of Transferrin and thereby iron uptake by SIV Nef might limit viral replication in myeloid cells. Furthermore, this new SIV Nef function could represent a virus-host adaptation that evolved in natural SIV-infected monkeys. PMID:24383984

Ligand-controlled assembly of Cd(II) coordination polymers based on mixed ligands of naphthalene-dicarboxylate and dipyrido[3,2-d:2',3'-f]quinoxaline: From 0D+1D cocrystal, 2D rectangular network (4,4), to 3D PtS-type architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Guocheng; Chen Yongqiang; Wang Xiuli

Three novel Cd(II) coordination polymers, namely, [Cd(Dpq)(1,8-NDC)(H{sub 2}O){sub 2}][Cd(Dpq)(1,8-NDC)].2H{sub 2}O (1), [Cd(Dpq)(1,4-NDC)(H{sub 2}O)] (2), and [Cd(Dpq)(2,6-NDC)] (3) have been obtained from hydrothermal reactions of cadmium(II) nitrate with the mixed ligands dipyrido [3,2-d:2',3'-f]quinoxaline (Dpq) and three structurally related naphthalene-dicarboxylate ligands [1,8-naphthalene-dicarboxylic acid (1,8-H{sub 2}NDC), 1,4-naphthalene-dicarboxylic acid (1,4-H{sub 2}NDC), and 2,6-naphthalene-dicarboxylic acid (2,6-H{sub 2}NDC)]. Single-crystal X-ray diffraction analysis reveals that the three polymers exhibit novel structures due to different naphthalene-dicarboxylic acid. Compound 1 is a novel cocrystal of left- and right-handed helical chains and binuclear complexes and ultimately packed into a 3D supramolecular structure through hydrogen bonds and {pi}-{pi} stacking interactions. Compoundmore » 2 shows a 2D rectangular network (4,4) bridged by 1,4-NDC with two kinds of coordination modes and ultimately packed into a 3D supramolecular structure through inter-layer {pi}-{pi} stacking interactions. Compound 3 is a new 3D coordination polymer with distorted PtS-type network. In addition, the title compounds exhibit blue/green emission in solid state at room temperature. - Graphical abstract: Three novel Cd(II) compounds have been synthesized under hydrothermal conditions exhibiting a systematic variation of architecture by the employment of three structurally related naphthalene-dicarboxylate ligands.« less

Green-synthesized CdS nano-pesticides: Toxicity on young instars of malaria vectors and impact on enzymatic activities of the non-target mud crab Scylla serrata.

PubMed

Sujitha, Vasu; Murugan, Kadarkarai; Dinesh, Devakumar; Pandiyan, Amuthvalli; Aruliah, Rajasekar; Hwang, Jiang-Shiou; Kalimuthu, Kandasamy; Panneerselvam, Chellasamy; Higuchi, Akon; Aziz, Al Thabiani; Kumar, Suresh; Alarfaj, Abdullah A; Vaseeharan, Baskaralingam; Canale, Angelo; Benelli, Giovanni

2017-07-01

Currently, nano-formulated mosquito larvicides have been widely proposed to control young instars of malaria vector populations. However, the fate of nanoparticles in the aquatic environment is scarcely known, with special reference to the impact of nanoparticles on enzymatic activity of non-target aquatic invertebrates. In this study, we synthesized CdS nanoparticles using a green protocol relying on the cheap extract of Valoniopsis pachynema algae. CdS nanoparticles showed high toxicity on young instars of the malaria vectors Anopheles stephensi and A. sundaicus. The antimalarial activity of the nano-synthesized product against chloroquine-resistant (CQ-r) Plasmodium falciparum parasites was investigated. From a non-target perspective, we focused on the impact of this novel nano-pesticide on antioxidant enzymes acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities of the mud crab Scylla serrata. The characterization of nanomaterials was carried out by UV-vis and FTIR spectroscopy, as well as SEM and XRD analyses. In mosquitocidal assays, LC 50 of V. pachynema-synthesized CdS nanoparticles on A. stephensi ranged from 16.856 (larva I), to 30.301μg/ml (pupa), while for An. sundaicus they ranged from 13.584 to 22.496μg/ml. The antiplasmodial activity of V. pachynema extract and CdS nanoparticles was evaluated against CQ-r and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. IC 50 of V. pachynema extract was 58.1μg/ml (CQ-s) and 71.46μg/ml (CQ-r), while nano-CdS IC 50 was 76.14μg/ml (CQ-s) and 89.21μg/ml (CQ-r). In enzymatic assays, S. serrata crabs were exposed to sub-lethal concentrations, i.e. 4, 6 and 8μg/ml of CdS nanoparticles, assessing changes in GST and AChE activity after 16days. We observed significantly higher activity of GST, if compared to the control, during the whole experiment period. In addition, a single treatment with CdS nanoparticles led to a significant decrease in AChE activity over time. The toxicity of CdS nanoparticles and Cd ions in aqueous solution was also assessed in mud crabs, showing higher toxicity of aqueous Cd ions if compared to nano-CdS. Overall, our results underlined the efficacy of green-synthesized CdS nanoparticles in malaria vector control, outlining also significant impacts on the enzymatic activity of non-target aquatic organisms, with special reference to mud crabs. Copyright © 2017 Elsevier B.V. All rights reserved.

[Changes of FoxP3, CD4(+)CD25(+) regulatory T cells, TLR2 and TLR9 in children with infectious mononucleosis].

PubMed

Wang, Qiang; Wang, Zuo-Feng; Cao, Mei; Wang, Zhi-Ying

2013-04-01

The aim of this study was to investigate the effects of TLR2, TLR9, CD4(+)CD25(+) regulatory T cells (Treg) and transcription factor FoxP3 in the pathogenesis of children with infectious mononucleosis (IM). Thirty-five acute IM patients admitted in our hospital from April 2010 to January 2011 were enrolled in this study. Thirty-five healthy subjects were taken as control. The thirty-five patients before treatment were considered as patients in acute stage, after treatment and without clinical symptom they were thought as patients in recovery stage. The expression levels of TLR2, TLR9 and FoxP3 mRNA were detected by real time PCR using SYBR Green I. The expression of T lymphocyte subset CD4(+)CD25(+) in peripheral blood mononuclear cells was detected by flow cytometry. The results showed that the relative levels of TLR2 mRNA (4.03 ± 0.56), TLR9 mRNA (8.88 ± 1.56) in peripheral blood mononuclear cells of IM patients in acute stage were significantly higher than those of the controls [TLR2 mRNA (2.22 ± 0.57), TLR9 mRNA (3.63 ± 1.30)] and IM patients in recovery stage [TLR2 mRNA (2.76 ± 0.83), TLR9 mRNA (5.34 ± 1.60)] (P < 0.01). The result of CD4(+)CD25(+) (2.38 ± 1.32%) and relative level of FoxP3 mRNA(2.82 ± 0.90) in peripheral blood mononuclear cells of IM patients in acute stage were lower than those of the control [CD4(+)CD25(+) (7.85 ± 1.97%), FoxP3 mRNA (4.65 ± 1.23) ] (P < 0.01). There was no significant difference in CD4(+)CD25(+) (6.81 ± 1.84%), FoxP3 mRNA(4.11 ± 1.37) levels between IM patients in recovery stage and the controls (P > 0.05). It is concluded that the expression of CD4(+)CD25(+)regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is down-regulated, but expression levels of TLR2 mRNA, TLR9 mRNA are up-regulated in IM patients of acute stage.

The gene therapy revolution in ophthalmology.

PubMed

Al-Saikhan, Fahad I

2013-04-01

The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.

The gene therapy revolution in ophthalmology

PubMed Central

Al-Saikhan, Fahad I.

2013-01-01

The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber’s Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red–green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable. PMID:24227970

Ligand-controlled assembly of Cd(II) coordination polymers based on mixed ligands of naphthalene-dicarboxylate and dipyrido[3,2-d:2‧,3‧-f]quinoxaline: From 0D+1D cocrystal, 2D rectangular network (4,4), to 3D PtS-type architecture

NASA Astrophysics Data System (ADS)

Liu, Guocheng; Chen, Yongqiang; Wang, Xiuli; Chen, Baokuan; Lin, Hongyan

2009-03-01

Three novel Cd(II) coordination polymers, namely, [Cd(Dpq)(1,8-NDC)(H 2O) 2][Cd(Dpq)(1,8-NDC)]·2H 2O ( 1), [Cd(Dpq)(1,4-NDC)(H 2O)] ( 2), and [Cd(Dpq)(2,6-NDC)] ( 3) have been obtained from hydrothermal reactions of cadmium(II) nitrate with the mixed ligands dipyrido [3,2-d:2',3'-f]quinoxaline (Dpq) and three structurally related naphthalene-dicarboxylate ligands [1,8-naphthalene-dicarboxylic acid (1,8-H 2NDC), 1,4-naphthalene-dicarboxylic acid (1,4-H 2NDC), and 2,6-naphthalene-dicarboxylic acid (2,6-H 2NDC)]. Single-crystal X-ray diffraction analysis reveals that the three polymers exhibit novel structures due to different naphthalene-dicarboxylic acid. Compound 1 is a novel cocrystal of left- and right-handed helical chains and binuclear complexes and ultimately packed into a 3D supramolecular structure through hydrogen bonds and π- π stacking interactions. Compound 2 shows a 2D rectangular network (4,4) bridged by 1,4-NDC with two kinds of coordination modes and ultimately packed into a 3D supramolecular structure through inter-layer π- π stacking interactions. Compound 3 is a new 3D coordination polymer with distorted PtS-type network. In addition, the title compounds exhibit blue/green emission in solid state at room temperature.

Continuous blade coating for multi-layer large-area organic light-emitting diode and solar cell

NASA Astrophysics Data System (ADS)

Chen, Chun-Yu; Chang, Hao-Wen; Chang, Yu-Fan; Chang, Bo-Jie; Lin, Yuan-Sheng; Jian, Pei-Siou; Yeh, Han-Cheng; Chien, Hung-Ta; Chen, En-Chen; Chao, Yu-Chiang; Meng, Hsin-Fei; Zan, Hsiao-Wen; Lin, Hao-Wu; Horng, Sheng-Fu; Cheng, Yen-Ju; Yen, Feng-Wen; Lin, I.-Feng; Yang, Hsiu-Yuan; Huang, Kuo-Jui; Tseng, Mei-Rurng

2011-11-01

A continuous roll-to-roll compatible blade-coating method for multi-layers of general organic semiconductors is developed. Dissolution of the underlying film during coating is prevented by simultaneously applying heating from the bottom and gentle hot wind from the top. The solvent is immediately expelled and reflow inhibited. This method succeeds for polymers and small molecules. Uniformity is within 10% for 5 cm by 5 cm area with a mean value of tens of nanometers for both organic light-emitting diode (OLED) and solar cell structure with little material waste. For phosphorescent OLED 25 cd/A is achieved for green, 15 cd/A for orange, and 8 cd/A for blue. For fluorescent OLED 4.3 cd/A is achieved for blue, 9 cd/A for orange, and 6.9 cd/A for white. For OLED with 2 cm by 3 cm active area, the luminance variation is within 10%. Power conversion efficiency of 4.1% is achieved for polymer solar cell, similar to spin coating using the same materials. Very-low-cost and high-throughput fabrication of efficient organic devices is realized by the continuous blade-only method.

[Experimental study of glioma stem cell-mediated immune tolerance in tumor microenvironment].

PubMed

Xie, T; Ma, J W; Liu, B; Dong, J; Huang, Q

2017-11-23

Objective: To investigate the tumor microenvironment of immune tolerance induced by glioma stem cells (GSC). Methods: Human GSC SU3 cells transfected with red fluorescent protein (SU3-RFP) gene were implanted into the brain, subcutis (armpit and foot), liver and abdominal cavity of transgenic green fluorescence protein (GFP) nude mice to establish RFP(+) /GFP(+) dual fluorescence solid tumor model. The re-cultured cells derived from implanted tumor tissues, SU3-RFP cells co-cultured with peritoneal fluid of transgenic GFP nude mice and malignant ascites of tumor-bearing mice were observed by fluorescence microscopy and real-time video image tracing to analyze the microenvironment of immune tolerance mediated by RFP(+) /GFP(+) implanted tumor. Results: Dual fluorescence labeled frozen section showed that all of cells in the tumor microenvironment were GFP(+) , while the pressed tissue-patch showed that the tumor blood vessels exhibited a RFP(+) /GFP(+) double-positioning yellow. In the GFP single fluorescence labeled tumor tissue, all of cells in the microenvironment were green, including tumor edge, necrotic foci and blood vessel. Among them, CD68(+) , F4/80(+) , CD11c(+) , CD11b(+) and CD80(+) cells were observed. In the dual fluorescence labeled co-cultured cells, the phagocytosis and fusion between green host cells and red tumor cells were also observed, and these fusion cells might transfer to the malignant dendritic cells and macrophages. Conclusions: The tumor microenvironment of immune tolerance induced by GSC is not affected by the tissue types of tumor-inoculated sites, and the immune tolerance mediated by inflammatory cells is associated with the inducible malignant transformation, which may be driven by cell fusion.

Spacelab 4: Primate experiment support hardware

NASA Astrophysics Data System (ADS)

Fusco, P. R.; Peyran, R. J.

1984-05-01

A squirrel monkey feeder and automatic urine collection system were designed to fly on the Spacelab 4 Shuttle Mission presently scheduled for January 1986. Prototypes of the feeder and urine collection systems were fabricated and extensively tested on squirrel monkeys at the National Aeronautics and Space Administration's (NASA) Ames Research Center (ARC). The feeder design minimizes impact on the monkey's limited space in the cage and features improved reliability and biocompatibility over previous systems. The urine collection system is the first flight qualified, automatic urine collection device for squirrel monkeys. Flight systems are currently being fabricated.

Spacelab 4: Primate experiment support hardware

NASA Technical Reports Server (NTRS)

Fusco, P. R.; Peyran, R. J.

1984-01-01

A squirrel monkey feeder and automatic urine collection system were designed to fly on the Spacelab 4 Shuttle Mission presently scheduled for January 1986. Prototypes of the feeder and urine collection systems were fabricated and extensively tested on squirrel monkeys at the National Aeronautics and Space Administration's (NASA) Ames Research Center (ARC). The feeder design minimizes impact on the monkey's limited space in the cage and features improved reliability and biocompatibility over previous systems. The urine collection system is the first flight qualified, automatic urine collection device for squirrel monkeys. Flight systems are currently being fabricated.

Muscimol inactivation of caudal fastigial nucleus and posterior interposed nucleus in monkeys with strabismus.

PubMed

Joshi, Anand C; Das, Vallabh E

2013-10-01

Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in strabismic monkeys. The SOA receives afferent projections from the caudal fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the cerebellum. The objectives of the present study were to investigate the potential roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye alignment in strabismic monkeys. We used unilateral injections of the GABAA agonist muscimol to reversibly inactivate the cFN (4 injections in exotropic monkey S1 with ≈ 4° of exotropia; 5 injections in esotropic monkey S2 with ≈ 34° of esotropia) and the PIN (3 injections in monkey S1). cFN inactivation induced horizontal saccade dysmetria in all experiments (mean 39% increase in ipsilesional saccade gain and 26% decrease in contralesional gain). Also, mean contralesional smooth-pursuit gain was decreased by 31%. cFN inactivation induced a divergent change in eye alignment in both monkeys, with exotropia increasing by an average of 9.8° in monkey S1 and esotropia decreasing by an average of 11.2° in monkey S2 (P < 0.001). Unilateral PIN inactivation in monkey S1 resulted in a mean increase in the gain of upward saccades by 13% and also induced a convergent change in eye alignment, reducing exotropia by an average of 2.7° (P < 0.001). We conclude that cFN/PIN influences on conjugate eye movements in strabismic monkeys are similar to those postulated in normal monkeys and cFN/PIN play important and complementary roles in maintaining the steady-state misalignment in strabismus.

Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

NASA Technical Reports Server (NTRS)

Sato, N.; Kiuchi, K.; Shen, Y. T.; Vatner, S. F.; Vatner, D. E.

1995-01-01

To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

Induction of allograft tolerance through costimulatory blockade: first selection of drugs in vitro.

PubMed

Vierboom, Michel P M; Ossevoort, Miriam; Sick, Ella A; Haanstra, Krista; Jonker, Margreet

2003-01-01

The development of an in vitro assay predicting the chances of graft survival after treatment with immunoregulatory agents is a major topic in transplantation. Antibodies (Abs) interfering in the costimulatory pathway are promising candidates for the induction of tolerance. To evaluate these antibodies for clinical use studies non-human primates are the only feasible option due to species specificity of the antibodies. Peripheral blood mononuclear cells, isolated from a large panel of rhesus monkeys, were used in a unidirectional mixed lymphocyte reaction to evaluate the ability of antibodies blocking the costimulatory pathway, to affect both primary and secondary proliferative and cytolytic allospecific immune responses in vitro. These blocking antibodies were also used in protocols prolonging allograft survival in a life-supporting kidney allotransplant model in rhesus macaques. The ultimate aim is to establish a correlation between parameters obtained in vitro and the success of transplantation in vivo. The combination of anti-CD80 and anti-CD86 resulted in a complete abrogation of the primary alloresponse as measured in a proliferation assay. Adding anti-CD40 significantly reduced this inhibitory effect although the in vivo effects of this antibody have been shown to be beneficial. The secondary response was most prominently inhibited by the combination of anti-CD80/86. Paradoxically, anti-CD40 alone markedly inhibited the secondary proliferative response, but did not add to the inhibitory effect of the combination of anti-CD80/86. The cytolytic response was inhibited maximally only when CsA was added to the combination of anti-CD80/86. Treatment with monoclonal antibodies alone without immunosuppressive drugs was sufficient to maintain graft survival during the time of treatment in most animals. However, rejection was initiated as soon as the treatment ceased and no tolerance, resulting in long-term graft and patient survival, was established. The complete inhibition of primary alloresponses and the partial inhibition of secondary proliferative alloresponses correlate with prolonged graft survival during treatment, but have no predictive value for the success of tolerance induction for kidney allografts in rhesus monkeys.

Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

PubMed

Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

2012-12-15

Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation. Copyright © 2012 Elsevier Inc. All rights reserved.

Analysis of the reptile CD1 genes: evolutionary implications.

PubMed

Yang, Zhi; Wang, Chunyan; Wang, Tao; Bai, Jianhui; Zhao, Yu; Liu, Xuhan; Ma, Qingwei; Wu, Xiaobing; Guo, Ying; Zhao, Yaofeng; Ren, Liming

2015-06-01

CD1, as the third family of antigen-presenting molecules, is previously only found in mammals and chickens, which suggests that the chicken and mammalian CD1 shared a common ancestral gene emerging at least 310 million years ago. Here, we describe CD1 genes in the green anole lizard and Crocodylia, demonstrating that CD1 is ubiquitous in mammals, birds, and reptiles. Although the reptilian CD1 protein structures are predicted to be similar to human CD1d and chicken CD1.1, CD1 isotypes are not found to be orthologous between mammals, birds, and reptiles according to phylogenetic analyses, suggesting an independent diversification of CD1 isotypes during the speciation of mammals, birds, and reptiles. In the green anole lizard, although the single CD1 locus and MHC I gene are located on the same chromosome, there is an approximately 10-Mb-long sequence in between, and interestingly, several genes flanking the CD1 locus belong to the MHC paralogous region on human chromosome 19. The CD1 genes in Crocodylia are located in two loci, respectively linked to the MHC region and MHC paralogous region (corresponding to the MHC paralogous region on chromosome 19). These results provide new insights for studying the origin and evolution of CD1.

Adaption of Ulva pertusa to multiple-contamination of heavy metals and nutrients: Biological mechanism of outbreak of Ulva sp. green tide.

PubMed

Ge, Changzi; Yu, Xiru; Kan, Manman; Qu, Chunfeng

2017-12-15

The multiple-contamination of heavy metals and nutrients worsens increasingly and Ulva sp. green tide occurs almost simultaneously. To reveal the biological mechanism for outbreak of the green tide, Ulva pertusa was exposed to seven-day-multiple-contamination. The relation between pH variation (V pH ), Chl a content, ratio of (Chl a content)/(Chl b content) (R chla/chlb ), SOD activity of U. pertusa (A SOD ) and contamination concentration is [Formula: see text] (p<0.05), C chla =0.88 ±0.09 -0.01 ±0.00 ×C Cd (p<0.05), [Formula: see text] (p<0.05), and [Formula: see text] (p<0.05), respectively. C ammonia , C Cd and C Zn is concentration of ammonia, Cd 2+ and Zn 2+ , respectively. Comparing the contamination concentrations of seawaters where Ulva sp. green tide occurred and the contamination concentrations set in the present work, U. pertusa can adapt to multiple-contaminations in these waters. Thus, the adaption to multiple-contamination may be one biological mechanism for the outbreak of Ulva sp. green tide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolism of 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-tetrachlorobenzene in the squirrel monkey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, H.; Chu, I.; Villeneuve, D.C.

1987-01-01

The metabolism of three tetrachlorobenzene isomers (TeCB) was investigated in the squirrel monkey. The animals were administered orally 6 single doses of /sup 14/C-labeled 1,2,3,4-, 1,2,4,5-, or 1,2,3,5-tetrachlorobenzene over a 3-wk period at levels ranging from 50 to 100 mg/kg body weight (b.w) and kept in individual metabolism cages to collect urine and feces for radioassay. Approximately 38% (1,2,3,4-TeCB), 36% (1,2,3,5-TeCB), and 18% (1,2,4,5-TeCB) of the doses were excreted respectively in the feces 48 h post administration. In monkeys dosed with 1,2,3,4-TeCB, unchanged compound accounted for 50% of the fecal radioactivity. Unchanged compound accounted for more than 50% of themore » fecal radioactivity found in the monkeys dosed with 1,2,3,5-TeCB. The fecal metabolites were identified in both groups. No metabolites were detected in the feces of monkeys dosed with 1,2,4,5-TeCB. While the fecal route represented the major route of excretion for 1,2,3,4-TeCB, the other two isomers were eliminated exclusively in the feces. The above data in the squirrel monkey are different from those obtained with the rat and the rabbit, and demonstrate the different metabolic pathways for the isomers.« less

Investigation into the mechanism(s) that leads to platelet decreases in cynomolgus monkeys during administration of ISIS-104838, a 2'-MOE-modified antisense oligonucleotide.

PubMed

Narayanan, P K; Shen, L; Curtis, B R; Bourdon, M; Nolan, J P; Zhou, F; Christian, B; Gupta, S; Schaubhut, J L; Greenlee, S; Hoffmaster, C; Burel, S; Witztum, J L; Engelhardt, J A; Henry, S P

2018-05-29

ISIS 104838, a 2'-O-methoxyethyl (2'-MOE)-modified antisense oligonucleotide (ASO), causes a moderate, reproducible, dose-dependent, but self-limiting decrease in platelet (PLT) counts in monkeys and humans. To determine the etiology of PLT decrease in cynomolgus monkeys, a 12-week repeat dose toxicology study in 5 cynomolgus monkeys given subcutaneous injections of ISIS 104838 (30 to 60 mg/kg/week). Monkeys were also injected intravenously with 111In-oxine-labeled PLTs to investigate PLT sequestration. In response to continued dosing, PLT counts were decreased by 50 to 90% by day 30 in all monkeys. PLT decreases were accompanied by 2- to 4.5-fold increases in immunoglobulin M(IgM), which were typified by a 2-to-5-fold increase in anti-platelet factor 4 (PF4) IgM and anti-PLT IgM, respectively. Monocyte chemotactic protein 1 (MCP-1) increased upon dosing of ISIS 104838, concomitant with a 2- to 6-fold increase in monocyte-derived extracellular vesicles (EVs), indicating monocyte activation but not PLT activation. Despite a 2- to- 3-fold increase in von Willebrand factor (VWF) antigen in all monkeys following ASO administration, only two monkeys showed a 2 to 4-fold increase in endothelial EVs. Additionally, a 25-45% increase in PLT sequestration in liver and spleen was also observed. Collectively, these results suggest the overall increase in total IgM, anti-PLT IgM and/or anti-PF4 IgM, in concert with monocyte activation contributed to increased PLT sequestration in spleen and liver, leading to decreased PLTs in peripheral blood.

Two separable functional domains of simian virus 40 large T antigen: carboxyl-terminal region of simian virus 40 large T antigen is required for efficient capsid protein synthesis.

PubMed Central

Tornow, J; Polvino-Bodnar, M; Santangelo, G; Cole, C N

1985-01-01

The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T antigen lacks those residues known to be required for adenovirus helper function, and the block to productive infection by dlA2459 occurs at the same stage of infection as the block to productive adenovirus infection of CV-1 cells. These results suggest that the adenovirus helper function is required for productive infection by simian virus 40. Mutant dlA2459 was able to grow on the Vero and BSC-1 lines of African green monkey kidney cells. Additional mutants affecting the carboxyl-terminal portion of large T were prepared. Mutant inv2408 contains an inversion of the DNA between the BamHI and BclI sites (0.144 to 0.189 map units). This inversion causes transposition of the carboxyl-terminal 26 amino acids of large T antigen and the carboxyl-terminal 18 amino acids of VP1. This mutant was viable, even though the essential information absent from dlA2459 large T antigen has been transferred to the carboxyl terminus of VP1 of inv2408. The VP1 polypeptide carrying this carboxyl-terminal portion of large T could overcome the defect of dlA2459. This indicates that the carboxyl terminus of large T antigen is a separate and separable functional domain. Images PMID:2982029

An assessment of domain-general metacognitive responding in rhesus monkeys.

PubMed

Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

2017-02-01

Metacognition is the ability to monitor and control one's cognition. Monitoring may involve either public cues or introspection of private cognitive states. We tested rhesus monkeys (Macaca mulatta) in a series of generalization tests to determine which type of cues control metacognition. In Experiment 1, monkeys learned a perceptual discrimination in which a "decline-test" response allowed them to avoid tests and receive a guaranteed small reward. Monkeys declined more difficult than easy tests. In Experiments 2-4, we evaluated whether monkeys generalized this metacognitive responding to new perceptual tests. Monkeys showed a trend toward generalization in Experiments 2 & 3, and reliable generalization in Experiment 4. In Experiments 5 & 6, we presented the decline-test response in a delayed matching-to-sample task. Memory tests differed from perceptual tests in that the appearance of the test display could not control metacognitive responding. In Experiment 6, monkeys made prospective metamemory judgments before seeing the tests. Generalization across perceptual tests with different visual properties and mixed generalization from perceptual to memory tests provide provisional evidence that domain-general, private cues controlled metacognition in some monkeys. We observed individual differences in generalization, suggesting that monkeys differ in use of public and private metacognitive cues. Copyright © 2016 Elsevier B.V. All rights reserved.

Convenient synthesis of twin-Christmas tree-like PbWO4 microcrystals and their photocatalytic properties

NASA Astrophysics Data System (ADS)

Zhang, Jin; Peng, Li-Li; Tang, Ying; Wu, Huijie

2017-06-01

Novel twin-Christmas tree-like PbWO4 microcrystals have been prepared via a convenient aqueous solution route at room temperature under the assistance of β-cyclodextrin (β-CD). The product was characterized by XRD, EDX, SEM, TEM, UV-vis and PL and BET techniques. It was found that β-CD plays an important role in the forming of twin-Christmas tree-like PbWO4 microcrystals. A five-step growth mechanism was proposed to explain the formation of such twin-Christmas tree-like structures. The photocatalytic performance of PbWO4 microcrystals was evaluated by measuring the decomposition rate of methylene blue (MB) and malachite green (MG) solution under the UV irradiation, and the photocatalytic results indicated that as-prepared PbWO4 microcrystals exhibit good and versatile photocatalytic activity as well as excellent recyclability.

Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

PubMed

Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

2006-08-01

Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green fluorescent protein positive cells in the epithelial compartment 14 days after injury expressed cytokeratin 5/8, similar to the proportion of green fluorescent protein positive cells in the prostate that no longer expressed the hematopoietic marker CD45. When prostatic degeneration/regeneration was triggered by androgen deprivation and reintroduction, no green fluorescent protein positive prostate epithelial cells were detected. These findings are consistent with a requirement for inflammation associated architectural destruction for the bone marrow derived cell contribution to the regeneration of prostate epithelium.

Biomarkers for non-human primate type-I hypersensitivity: antigen-specific immunoglobulin E assays.

PubMed

Clark, Darcey; Shiota, Faith; Forte, Carla; Narayanan, Padma; Mytych, Daniel T; Hock, M Benjamin

2013-06-28

Immunoglobulin E (IgE) is the least abundant immunoglobulin in serum. However, development of an IgE immune response can induce IgE receptor-expressing cells to carry out potent effector functions. A reliable antigen-specific IgE biomarker method for use in non-human primate studies would facilitate (i) confirmation of Type-I hypersensitivity reactions during safety toxicology testing, and (ii) a better understanding of non-human primate models of allergic disease. We cloned and expressed a recombinant cynomolgus monkey IgE molecule in order to screen a panel of commercially available detection reagents raised against human IgE for cross-reactivity. The reagent most reactive to cynomolgus IgE was confirmed to be specific for IgE and did not bind recombinant cynomolgus monkey IgG1-4. A drug-specific IgE assay was developed on the MSD electrochemiluminescent (ECL) platform. The assay is capable of detecting 10 ng/mL drug-specific IgE. Importantly, the assay is able to detect IgE in the presence of excess IgG, the scenario likely to be present in a safety toxicology study. Using our ECL assay, we were able to confirm that serum from cynomolgus monkeys that had experienced clinical symptoms consistent with hypersensitivity responses contained IgE specific for a candidate therapeutic antibody. In addition, a bioassay for mast cell activation was developed using CD34(+)-derived cynomolgus monkey mast cells. This assay confirmed that plasma from animals identified as positive in the drug-specific IgE immunoassay contained biologically active IgE (i.e. could sensitize cultured mast cells), resulting in histamine release after exposure to the therapeutic antibody. These sensitive assays for Type-I hypersensitivity in the NHP can confirm that secondary events are downstream of immunogenicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Efficient exciton generation in atomic passivated CdSe/ZnS quantum dots light-emitting devices

PubMed Central

Kang, Byoung-Ho; Lee, Jae-Sung; Lee, Sang-Won; Kim, Sae-Wan; Lee, Jun-Woo; Gopalan, Sai-Anand; Park, Ji-Sub; Kwon, Dae-Hyuk; Bae, Jin-Hyuk; Kim, Hak-Rin; Kang, Shin-Won

2016-01-01

We demonstrate the first-ever surface modification of green CdSe/ZnS quantum dots (QDs) using bromide anions (Br-) in cetyl trimethylammonium bromide (CTAB). The Br- ions reduced the interparticle spacing between the QDs and induced an effective charge balance in QD light-emitting devices (QLEDs). The fabricated QLEDs exhibited efficient charge injection because of the reduced emission quenching effect and their enhanced thin film morphology. As a result, they exhibited a maximum luminance of 71,000 cd/m2 and an external current efficiency of 6.4 cd/A, both significantly better than those of their counterparts with oleic acid surface ligands. In addition, the lifetime of the Br- treated QD based QLEDs is significantly improved due to ionic passivation at the QDs surface. PMID:27686147

[Hybrids of human and monkey adenoviruses (adeno-adeno hybrids) that can reproduce in monkey cells: biological and molecular genetic peculiarities].

PubMed

Grinenko, N F; Savitskaia, N V; Pashvykina, G V; Al'tshteĭn, A D

2003-06-01

A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.

Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

PubMed

Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

2013-01-01

Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

Seroepidemiological survey of pathogenic Yersinia in breeding squirrel monkeys in Japan.

PubMed

Iwata, Taketoshi; Une, Yumi; Lee, Ken-ichi; Nakamura, Shin-ichi; Taniguchi, Takahide; Hayashidani, Hideki

2010-08-01

To investigate the prevalence of antibodies to pathogenic Yersinia in breeding squirrel monkeys, the serum samples of 252 squirrel monkeys from 9 zoological gardens in Japan were tested by ELISA using plasmid-encoded Yersinia outer membrane protein (Yops) as the antigen. The cutoff value was calculated by using the serum samples of the squirrel monkeys from Suriname, where no prevalence of pathogenic Yersinia have been reported. According to the cutoff value, 164 of 252 (65.1%) squirrel monkeys were considered positive against pathogenic Yersinia. These positive monkeys belonged to 8 of the 9 zoological gardens, and the percentage of the seropositive monkeys ranged from 22.2 to 89.4%. Furthermore, in one zoological garden, the positive rate of the squirrel monkeys which were over 1 year old (95.7%) was significantly higher than those which were under 1 year old (23.3%). These results suggested that pathogenic Yersinia is highly prevalent among breeding monkeys in Japan.

Prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (ADC) when evaluation of higher doses in animals is limited by tolerability: Case study with an anti-CD33 ADC.

PubMed

Figueroa, Isabel; Leipold, Doug; Leong, Steve; Zheng, Bing; Triguero-Carrasco, Montserrat; Fourie-O'Donohue, Aimee; Kozak, Katherine R; Xu, Keyang; Schutten, Melissa; Wang, Hong; Polson, Andrew G; Kamath, Amrita V

2018-05-14

For antibody-drug conjugates (ADCs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. For molecules with non-linear pharmacokinetics (PK), this limited dose range may be insufficient to fully characterize the PK of the ADC and limits translation to humans. Mathematical PK models are frequently used for molecule selection during preclinical drug development and for translational predictions to guide clinical study design. Here, we present a practical approach that uses limited PK and receptor occupancy (RO) data of the corresponding unconjugated antibody to predict ADC PK when conjugation does not alter the non-specific clearance or the antibody-target interaction. We used a 2-compartment model incorporating non-specific and specific (target mediated) clearances, where the latter is a function of RO, to describe the PK of anti-CD33 ADC with dose-limiting neutropenia in cynomolgus monkeys. We tested our model by comparing PK predictions based on the unconjugated antibody to observed ADC PK data that was not utilized for model development. Prospective prediction of human PK was performed by incorporating in vitro binding affinity differences between species for varying levels of CD33 target expression. Additionally, this approach was used to predict human PK of other previously tested anti-CD33 molecules with published clinical data. The findings showed that, for a cytotoxic ADC with non-linear PK and limited preclinical PK data, incorporating RO in the PK model and using data from the corresponding unconjugated antibody at higher doses allowed the identification of parameters to characterize monkey PK and enabled human PK predictions.

Potential toxicity and affinity of triphenylmethane dye malachite green to lysozyme.

PubMed

Ding, Fei; Li, Xiu-Nan; Diao, Jian-Xiong; Sun, Ye; Zhang, Li; Ma, Lin; Yang, Xin-Ling; Zhang, Li; Sun, Ying

2012-04-01

Malachite green is a triphenylmethane dye that is used extensively in many industrial and aquacultural processes, generating environmental concerns and health problems to human being. In this contribution, the complexation between lysozyme and malachite green was verified by means of computer-aided molecular modeling, steady state and time-resolved fluorescence, and circular dichroism (CD) approaches. The precise binding patch of malachite green in lysozyme has been identified from molecular modeling and ANS displacement, Trp-62, Trp-63, and Trp-108 residues of lysozyme were earmarked to possess high-affinity for this dye, the principal forces in the lysozyme-malachite green adduct are hydrophobic and π-π interactions. Steady state fluorescence proclaimed the complex of malachite green with lysozyme yields quenching through static type, which substantiates time-resolved fluorescence measurements that lysozyme-malachite green conjugation formation has an affinity of 10(3)M(-1). Moreover, via molecular modeling and also CD data, we can safely arrive at a conclusion that the polypeptide chain of lysozyme partially destabilized upon complexation with malachite green. The data emerged here will help to further understand the toxicological action of malachite green in human body. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficacy of an Adenovirus-based Anti-cocaine Vaccine to Reduce Cocaine Self-administration and Reacqusition using a Choice Procedure in Rhesus Macaques

PubMed Central

Evans, Suzette M.; Foltin, Richard W.; Hicks, Martin J.; Rosenberg, Jonathan B.; De, Bishnu P.; Janda, Kim D.; Kaminsky, Stephen M.; Crystal, Ronald G.

2016-01-01

Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1 mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6–41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57–94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy. PMID:27697554

Adipocytes impair efficacy of antiretroviral therapy.

PubMed

Couturier, Jacob; Winchester, Lee C; Suliburk, James W; Wilkerson, Gregory K; Podany, Anthony T; Agarwal, Neeti; Xuan Chua, Corrine Ying; Nehete, Pramod N; Nehete, Bharti P; Grattoni, Alessandro; Sastry, K Jagannadha; Fletcher, Courtney V; Lake, Jordan E; Balasubramanyam, Ashok; Lewis, Dorothy E

2018-06-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

Adipocytes Impair Efficacy of Antiretroviral Therapy

PubMed Central

Couturier, Jacob; Winchester, Lee C.; Suliburk, James W.; Wilkerson, Gregory K.; Podany, Anthony T.; Agarwal, Neeti; Chua, Corrine Ying Xuan; Nehete, Pramod N.; Nehete, Bharti P.; Grattoni, Alessandro; Sastry, K. Jagannadha; Fletcher, Courtney V.; Lake, Jordan E.; Balasubramanyan, Ashok; Lewis, Dorothy E.

2018-01-01

Adequate distribution of antiretroviral drugs to infected cells in HIV patients is critical for viral suppression. In humans and primates, HIV- and SIV-infected CD4 T cells in adipose tissues have recently been identified as reservoirs for infectious virus. To better characterize adipose tissue as a pharmacological sanctuary for HIV-infected cells, in vitro experiments were conducted to assess antiretroviral drug efficacy in the presence of adipocytes, and drug penetration in adipose tissue cells (stromal-vascular-fraction cells and mature adipocytes) was examined in treated humans and monkeys. Co-culture experiments between HIV-1-infected CD4 T cells and primary human adipocytes showed that adipocytes consistently reduced the antiviral efficacy of the nucleotide reverse transcriptase inhibitor tenofovir and its prodrug forms tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). In HIV-infected persons, LC-MS/MS analysis of intracellular lysates derived from adipose tissue stromal-vascular-fraction cells or mature adipocytes suggested that integrase inhibitors penetrate adipose tissue, whereas penetration of nucleoside/nucleotide reverse transcriptase inhibitors such as TDF, emtricitabine, abacavir, and lamivudine is restricted. The limited distribution and functions of key antiretroviral drugs within fat depots may contribute to viral persistence in adipose tissue. PMID:29630975

Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

PubMed Central

Jiang, George; Shi, Meng; Conteh, Solomon; Richie, Nancy; Banania, Glenna; Geneshan, Harini; Valencia, Anais; Singh, Priti; Aguiar, Joao; Limbach, Keith; Kamrud, Kurt I.; Rayner, Jonathan; Smith, Jonathan; Bruder, Joseph T.; King, C. Richter; Tsuboi, Takafumi; Takeo, Satoru; Endo, Yaeta; Doolan, Denise L.; Richie, Thomas L.; Weiss, Walter R.

2009-01-01

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost. PMID:19668343

Highly efficient inverted top emitting organic light emitting diodes using a transparent top electrode with color stability on viewing angle

NASA Astrophysics Data System (ADS)

Kim, Jung-Bum; Lee, Jeong-Hwan; Moon, Chang-Ki; Kim, Jang-Joo

2014-02-01

We report a highly efficient phosphorescent green inverted top emitting organic light emitting diode with excellent color stability by using the 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile/indium zinc oxide top electrode and bis(2-phenylpyridine)iridium(III) acetylacetonate as the emitter in an exciplex forming co-host system. The device shows a high external quantum efficiency of 23.4% at 1000 cd/m2 corresponding to a current efficiency of 110 cd/A, low efficiency roll-off with 21% at 10 000 cd/m2 and low turn on voltage of 2.4 V. Especially, the device showed very small color change with the variation of Δx = 0.02, Δy = 0.02 in the CIE 1931 coordinates as the viewing angle changes from 0° to 60°. The performance of the device is superior to that of the metal/metal cavity structured device.

Low roll-off and high efficiency orange OLEDs using green and red dopants in an exciplex forming co-host

NASA Astrophysics Data System (ADS)

Lee, Sunghun; Kim, Kwon-Hyeon; Yoo, Seung-Jun; Park, Young-Seo; Kim, Jang-Joo

2013-09-01

We present high efficiency orange emitting OLEDs with low driving voltage and low roll-off of efficiency using an exciplex forming co-host by (1) co-doping of green and red emitting phosphorescence dyes in the host and (2) red and green phosphorescent dyes doped in the host as separate red and green emitting layers. The orange OLEDs achieved a low turn-on voltage of 2.4 V and high external quantum efficiencies (EQE) of 25.0% and 22.8%, respectively. Moreover, the OLEDs showed low roll-off of efficiency with an EQE of over 21% and 19.6% at 10,000 cd/m2, respectively. The devices displayed good orange color with very little color shift with increasing luminance. The transient electroluminescence of the OLEDs indicated that both energy transfer and direct charge trapping took place in the devices.

Molecular characterization of Blastocystis isolates from children and rhesus monkeys in Kathmandu, Nepal.

PubMed

Yoshikawa, Hisao; Wu, Zhiliang; Pandey, Kishor; Pandey, Basu Dev; Sherchand, Jeevan Bahadur; Yanagi, Tetsuo; Kanbara, Hiroji

2009-03-23

To investigate the possible transmission of Blastocystis organisms between local rhesus monkeys and children in Kathmandu, Nepal, we compared the subtype (ST) and sequence of Blastocystis isolates from children with gastrointestinal symptoms and local rhesus monkeys. Twenty and 10 Blastocystis isolates were established from 82 and 10 fecal samples obtained from children and monkeys, respectively. Subtype analysis with seven sequence-tagged site (STS) primers indicated that the prevalence of Blastocystis sp. ST1, ST2 and ST3 was 20%, 20% and 60% in the child isolates, respectively. In contrast to human isolates, ST3 was not found in monkey isolates and the prevalence of ST1 and ST2 was 50% and 70%, respectively, including three mixed STs1 and 2 and one isolate not amplified by any STS primers, respectively. Since Blastocystis sp. ST2 has been reported as the most dominant genotype in the survey of Blastocystis infection among the various monkey species, sequence comparison of the 150bp variable region of the small subunit rRNA (SSU rRNA) gene was conducted among ST2 isolates of humans and monkeys. Sequence alignment of 24 clones developed from ST2 isolates of 4 humans and 4 monkeys showed three distinct subgroups, defined as ST2A, ST2B and ST2C. These three subgroups were shared between the child and monkey isolates. These results suggest that the local rhesus monkeys are a possible source of Blastocystis sp. ST2 infection of humans in Kathmandu.

EXPERIMENTS ON THE TRANSMISSION OF SCARLET FEVER TO THE LOWER MONKEYS

PubMed Central

Draper, George; Hanford, John M.

1913-01-01

1. The reported successful transfer of scarlet fever to both higher and lower monkeys is not definitely established. 2. In the course of the experiments here reported, the infectious agent can be assumed to have been carried over to the monkeys. The failure to cause infection probably proceeds from the insusceptibility of the monkeys employed, or to the manner of introducing the agent. 3. The temperature curve and leucocyte count of monkeys are unsatisfactory criteria for the diagnosis of disease in those animals. 4. Monkeys frequently have transient blotchy, erythematous eruptions on the face and neck, and almost always a bran-like desquamation. 5. Monkeys are highly resistant to infection with microorganisms from human beings. PMID:19867663

Tracking Monocyte Recruitment and Macrophage Accumulation in Atherosclerotic Plaque Progression Using a Novel hCD68GFP/ApoE−/− Reporter Mouse—Brief Report

PubMed Central

Iqbal, Asif J.; Jones, Daniel; Patel, Jyoti; Coutinho, Patricia; Taylor, Lewis; Greaves, David R.; Channon, Keith M.

2017-01-01

Objective— To create a model of atherosclerosis using green fluorescent protein (GFP)–targeted monocytes/macrophages, allowing analysis of both endogenous GFP+ and adoptively transferred GFP+ myeloid cells in arterial inflammation. Approach and Results— hCD68GFP reporter mice were crossed with ApoE−/− mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II–induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP+ expression in CD11b+/CD64+, CD11c+/MHC-IIHI, and CD11b+/F4/80+ myeloid cells. Adoptive transfer of GFP+ monocytes demonstrated monocyte recruitment to both adventitia and atherosclerotic plaque, throughout the aortic root, within 72 hours. We demonstrated the biological utility of hCD68GFP monocytes by comparing the recruitment of wild-type and CCR2−/− monocytes to sites of inflammation. Conclusions— hCD68GFP/ApoE−/− mice provide a new approach to study macrophage accumulation in atherosclerotic plaque progression and to identify cells recruited from adoptively transferred monocytes. PMID:27908893

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Bing; Shen, Chao; Zhang, Mengya

Green synthesis of CdSe quantum dots for application in the quantum-dots-sensitized solar cells (QDSCs) is investigated in this work. The CdSe QDs were prepared with glycerol as the solvent, with sharp emission peak, full width at half maximum around 30 nm, and absorption peak from 475 nm to 510 nm. The reaction is environmental friendly and energy saving. What's more, the green synthesized CdSe QDs are coherence to the maximum remittance region of the solar spectrum and suitable as sensitizers to assemble onto TiO{sub 2} electrodes for cell devices application. What's more, the dynamic procedure of the carriers' excitation, transportation, and recombination inmore » the QDSCs are discussed. Because the recombination of the electrons from the conduction band of TiO{sub 2}'s to the electrolyte affects the efficiency of the solar cells greatly, 3-Mercaptopropionic acid capped water-dispersible QDs were used to cover the surface of TiO{sub 2}. The resulting green synthesized CdSe QDSCs with Cu{sub 2}S as the electrode show a photovoltaic performance with a conversion efficiency of 3.39%.« less

Characterization of ovarian aging and reproductive senescence in vervet monkeys (Chlorocebus aethiops sabaeus).

PubMed

Atkins, Hannah M; Willson, Cynthia J; Silverstein, Marnie; Jorgensen, Matthew; Floyd, Edison; Kaplan, Jay R; Appt, Susan E

2014-02-01

Female vervet monkeys (Chlorocebus aethiops sabaeus) are used as an experimental model for chronic diseases relevant to women's health. However, reproductive senescence (menopause) has not yet been characterized for vervet monkeys. Here we describe the histologic, hormonal, and menstrual markers of reproductive senescence in vervet monkeys from the Wake Forest Vervet Research Colony. Ovaries from monkeys (age, 0 to 27 y) were serially sectioned (5 μm), stained, and photographed. In every 100th section, the numbers of primordial, primary, and secondary follicles were determined, and triplicate measurements were used to calculate mean numbers of follicles per ovary. Antimüllerian hormone (AMH), follicle stimulating hormone, and menstrual cycle length were measured in additional monkeys. Primordial follicles and AMH decreased significantly with age, and significant correlations between numbers of primordial and primary follicles and between numbers of primary and secondary follicles were noted. Histologic evaluation revealed that ovaries from 4 aged monkeys (older than 23 y) were senescent. One aged monkey transitioned to menopause, experiencing cycle irregularity over 4 y, eventual cessation of menses, and plasma AMH below the level of detection. Finally, with increasing age, the percentage of female vervets with offspring declined significantly. The present study provides insight into ovarian aging and reproductive senescence in vervet monkeys. Results highlight the importance of considering this nonhuman primate as a model to investigate the relationships between ovarian aging and chronic disease risk.

Successful construction and stable expression of an anti-CD45RA scFv-EGFP fusion protein in Chinese hamster ovary cells.

PubMed

Wang, Zhujun; Chen, Yuanyuan; Li, Sisi; Cheng, Yuping; Zhao, Haizhao; Jia, Ming; Luo, Zebin; Tang, Yongmin

2014-02-01

CD45RA has been found highly expressed on leukemia cells and may be a potential target of the disease. In this study, an anti-CD45RA single-chain antibody fragment (scFv3A4) was genetically linked to the N terminus of the enhanced green fluorescent protein (EGFP) to generate a scFv3A4-EGFP fusion protein. The scFv3A4-EGFP with a molecular weight of 57kDa was stably expressed and secreted from the transfected CHO cells through the ER/Golgi-dependent pathway. The fusion protein was soluble in the culture supernatant and the yield was 1350μg/L. Flow cytometry analysis showed that the scFv3A4-EGFP had the same binding site and a very similar reactivity pattern with its parental murine monoclonal antibody (mAb) 3A4. Furthermore, comparing to conventional labeled 3A4-FITC antibody, the scFv3A4-EGFP was more resistant to illumination and more suitable for immunofluorescence histology (IFH) detection. Therefore, the scFv3A4-EGFP fusion protein can be a powerful tool to investigate the targeting of CD45RA on leukemia cells, biological activity of the target and possibly for the genetic manipulation of the antibody. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparative Sensitivity of Tissue Cultures to Rubella Virus: Use of Guinea Pig Cells for Virus Titration

PubMed Central

Horta-Barbosa, L.; Warren, Joel

1969-01-01

A series of 19 different primary and serial tissue cultures were investigated for their sensitivity to virulent or attenuated rubella virus (RV). Primary guinea pig tissues, a serial passage of baby hamster kidney, and primary human amnion were comparable to African green monkey kidney tissue cultures in their sensitivity. In general, primary human tissues were relatively insusceptible to the Gilchrist strain of RV. RV interfered with the growth of vesicular stomatitis virus. Based on this finding, it was possible to develop an assay method in guinea pig tissue cultures by using VSV as the challenge virus. This system appeared to be comparable in sensitivity to the use of primary monkey kidney tissue cultures for the detection of small amounts of RV and offers the advantages of economy, rapidity, and safety. PMID:4979943

Hematology and Clinical Chemistry Measures During and After Pregnancy and Age- and Sex-Specific Reference Intervals in African Green Monkeys (Chlorocebus aethiops sabaeus).

PubMed

Chichester, Lee; Gee, Melaney K; Jorgensen, Matthew J; Kaplan, Jay R

2015-07-01

Clinical decisions and experimental analyses often involve the assessment of hematology and clinical chemistry. Using clinical pathology to assess the health status of NHP in breeding colonies or data from studies than involve pregnancy can often be complicated by pregnancy status. This study had 2 objectives regarding the hematology and clinical chemistry of African green monkeys (AGM, Chlorocebus aethiops sabaeus): 1) to compare pregnant or recently postpartum animals with nonpregnant, nonlactating animals and 2) to create age- and sex-specific reference intervals. Subjects in this study were 491 AGM from the Vervet Research Colony of the Wake Forest University Primate Center. Results indicated that changes in BUN, serum total protein, albumin, ALP, GGT, calcium, phosphorus, sodium, potassium, cholesterol, total CO2, globulins, lipase, amylase, WBC, neutrophils, lymphocytes, platelets, RBC, Hgb, and Hct occur during pregnancy and the postpartum period. Age- and sex-specific reference intervals consistent with guidelines from the American Society for Veterinary Clinical Pathology were established and further expand the understanding of how to define health in AGM on the basis of clinical pathology. The combination of understanding the changes that occur in pregnancy and postpartum and expansive reference intervals will help guide clinical and experimental decisions.

Comparison of Saliva Collection Methods for the Determination of Salivary Cortisol Levels in Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), and African Green Monkeys (Chlorocebus aethiops)

PubMed Central

Rapp-Santos, Kamala J; Altamura, Louis A; Norris, Sarah L; Lugo-Roman, Luis A; Rico, Pedro J; Hofer, Christian C

2017-01-01

The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA. In addition, both saliva collection methods were evaluated for volume collected and ease of use. Compared with passive drool, the experimental collection device was more reliable in collecting sufficient volumes of saliva, and the resulting salivary cortisol values demonstrated stronger correlation with serum cortisol concentration in all species and collection days except cynomolgus macaques on day 1. This saliva collection device allows quick and reliable sample collection for the determination of salivary cortisol levels. In addition, the results might provide a useful tool for evaluating hypothalamic-pituitary-adrenal axis activity or the physiologic stress reaction in NHP as well as a biomarker of psychologic stress states in a variety of situations. PMID:28315649

Serotypic characterization of rotaviruses derived from asymptomatic human neonatal infections.

PubMed Central

Hoshino, Y; Wyatt, R G; Flores, J; Midthun, K; Kapikian, A Z

1985-01-01

Nineteen rotavirus strains derived from asymptomatic neonates (seven from England, five from Australia, two from Venezuela, and five from Sweden) were successfully cultivated in primary African green monkey kidney cell cultures, serotyped by plaque reduction neutralization tests, subgrouped by indirect enzyme-linked immunosorbent assay, and electropherotyped by polyacrylamide gel electrophoresis. All 19 strains were shown to fall into one of the four known human serotypes; serotype 1 (all Venezuelan strains), serotype 2 (all Swedish strains), serotype 3 (all Australian strains), or serotype 4 (all English strains). Hyperimmune guinea pig serum raised against the Venezuelan strain (M37) neutralized not only serotype 1 (strain Wa) but also serotype 4 (strain St. Thomas no. 3) viruses to a similar degree. The English, Australian, and Venezuelan isolates were found to belong to subgroup 2, and the Swedish strains were subgroup 1 viruses. The potential importance of these rotaviruses obtained from neonates as possible vaccine candidates is discussed. Images PMID:2984247

Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

PubMed Central

Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

2006-01-01

CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (P<0.05) of CYP2B6 protein levels was observed in all regions tested (caudate, putamen, hippocampus, cerebellum, brain stem and frontal cortex) ranging from 2-fold to 150-fold. CYP2B6 expression was induced in specific cells, such as frontal cortical pyramidal cells and thalamic neurons. In conclusion, chronic phenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

DIETARY FAT AND HYPERCHOLESTEREMIA IN THE CEBUS MONKEY

PubMed Central

Portman, Oscar W.; Sinisterra, Leonardo

1957-01-01

A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C14. The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively. Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-14-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection. After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those of monkeys fed lard. Monkeys were fasted before and after intragastric administration of cholesterol-4-C14 in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol absorption. PMID:13475627

Studies of Scleral Biomechanical Behavior Related to Susceptibility for Retinal Ganglion Cell Loss in Experimental Mouse Glaucoma

PubMed Central

Nguyen, Cathy; Cone, Frances E.; Nguyen, Thao D.; Coudrillier, Baptiste; Pease, Mary E.; Steinhart, Matthew R.; Oglesby, Ericka N.; Jefferys, Joan L.; Quigley, Harry A.

2013-01-01

Purpose. To study anatomical changes and mechanical behavior of the sclera in mice with experimental glaucoma by comparing CD1 to B6 mice. Methods. Chronic experimental glaucoma for 6 weeks was produced in 2- to 4-month-old CD1 (43 eyes) and B6 mice (42 eyes) using polystyrene bead injection into the anterior chamber with 126 control CD1 and 128 control B6 eyes. Intraocular pressure (IOP) measurements were made with the TonoLab at baseline and after bead injection. Axial length and scleral thickness were measured after sacrifice in the CD1 and B6 animals and compared to length data from 78 eyes of DBA/2J mice. Inflation testing of posterior sclera was conducted, and circumferential and meridional strain components were determined from the displacement response. Results. Experimental glaucoma led to increases in axial length and width by comparison to fellow eyes (6% in CD1 and 10% in B6; all P < 0.03). While the peripapillary sclera became thinner in both mouse types with glaucoma, the remainder of the sclera uniformly thinned in CD1, but thickened in B6. Peripapillary sclera in CD1 controls had significantly greater temporal meridional strain than B6 and had differences in the ratios of meridional to effective circumferential strain from B6 mice. In both CD1 and B6 mice, exposure to chronic IOP elevation resulted in stiffer pressure–strain responses for both the effective circumferential and meridional strains (multivariable regression model, P = 0.01–0.03). Conclusions. Longer eyes, greater scleral strain in some directions at baseline, and generalized scleral thinning after glaucoma were characteristic of CD1 mice that have greater tendency to retinal ganglion cell damage than B6 mice. Increased scleral stiffness after glaucoma exposure in mice mimics findings in monkey and human glaucoma eyes. PMID:23404116

MicroRNA expressions in PMBCs, CD4+, and CD8+ T-cells from patients suffering from autoimmune Addison's disease.

PubMed

Bernecker, C; Halim, F; Haase, M; Willenberg, H S; Ehlers, M; Schott, M

2013-08-01

Autoimmune Addison's disease (AD) is a rare but potentially life threatening disease. The exact etiology of the immune response to the adrenal gland is still unknown. MicroRNAs (miRNAs) critically control gene-expression and play an important role in regulating the immune response. The aim of this study was to determine key immunoregulatory miRNAs influencing autoimmune adrenal insufficiency. For this purpose selected miRNAs were amplified by a semiquantitative SYBR Green PCR from blood mononuclear cells and after purification from CD4+ and CD 8+ cells of 6 patients with autoimmune adrenal insufficiency and 10 healthy controls. In CD4+ T-cells miRNA 181a*_1 (18.02 in AD vs. 11.99 in CG, p=0.0047) is significantly increased whereas miRNA 200a_1 (12.48 in AD vs. 19.40 in CG, p=0.0003) and miRNA 200a_2* (8.59 in AD vs. 17.94 in CG, p=0.0160) are significantly decreased. miRNA 200a_1 (12.37 in AD group vs. 18.12 in control group, p=0.001) and miRNA 200a_2* (10.72 in AD group vs. 17.84 in control group, p=0.022) are also significantly decreased in CD8+ T-cells. This study could show for the first time a significant change of three defined miRNAs in PBMCs, CD4+, and CD8+ T-cells of autoimmune AD patients in vivo. These data may help to better understand the cause of the autoimmune processes leading to autoimmune AD. They extend our very limited knowledge concerning miRNAs in autoimmune Addison's disease. © Georg Thieme Verlag KG Stuttgart · New York.

Isolation and characterization of an equine rotavirus.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

A rotavirus, designated as the H-1 strain, was isolated from a diarrheic foal in primary African green monkey kidney cells and MA104 cells. This cell culture-adapted strain hemagglutinated erythrocytes of human group O, rhesus monkeys, guinea pigs, and sheep. It was found to be similar, if not identical, to porcine rotaviruses (strains OSU, EE, and A-580) by plaque reduction neutralization and hemagglutination inhibition tests, and, in addition, it was found to belong to subgroup 1. This equine rotavirus has an RNA electrophoretic migration pattern which was distinct from those of the three strains of porcine rotavirus. The serological relationship established by plaque reduction neutralization and hemagglutination inhibition tests between the equine (H-1) and porcine (OSU, EE, and A-580) rotaviruses is an example of a rotavirus of the same serotype being isolated from different species. The H-1 strain was distinct from four human rotavirus serotypes (Wa, DS-1, P, and St. Thomas 4) as well as from bovine rotavirus NCDV, simian rotavirus MMU18006, and canine rotavirus CU-1 by plaque reduction neutralization tests. This equine isolate (H-1) was found to be related antigenically to canine CU-1 and bovine NCDV rotaviruses in a one-way fashion by hemagglutination inhibition tests. Images PMID:6313746

Computerized Color Vision Test Based Upon Postreceptoral Channel Sensitivities

PubMed Central

E, Miyahara; J, Pokorny; VC, Smith; E, Szewczyk; J, McCartin; K, Caldwell; A, Klerer

2006-01-01

An automated, computerized color vision test was designed to diagnose congenital red-green color vision defects. The observer viewed a yellow appearing CRT screen. The principle was to measure increment thresholds for three different chromaticities, the background yellow, a red, and a green chromaticity. Spatial and temporal parameters were chosen to favor parvocellular pathway mediation of thresholds. Thresholds for the three test stimuli were estimated by 4AFC, randomly interleaved staircases. Four 1.5°, 4.2 cd/m2 square pedestals were arranged as a 2 x 2 matrix around the center of the display with 15’ separations. A trial incremented all four squares by 1.0 cd/m2 for 133 msec. One randomly chosen square included an extra increment of a test chromaticity. The observer identified the different appearing square using the cursor. Administration time was ~5 minutes. Normal trichromats showed clear Sloan notch as defined by log (ΔY/ΔR), whereas red-green color defectives generally showed little or no Sloan notch, indicating that their thresholds were mediated by their luminance system, not by the chromatic system. Data from 107 normal trichromats showed a mean Sloan notch of 0.654 (SD = 0.123). Among 16 color vision defectives tested (2 protanopes, 1 protanomal, 6 deuteranopes, 7 deuteranomals), the Sloan notch was between −0.062 and 0.353 for deutans and was < −0.10 for protans. A sufficient number of color defective observers have not yet been tested to determine whether the test can reliably discriminate between protans and deutans. Nevertheless, the current data show that the test can work as a quick diagnostic procedure (functional trichromatism or dichromatism) of red-green color vision defect. PMID:15518231

Early adaptation to altered gravitational environments in the squirrel monkey

NASA Technical Reports Server (NTRS)

Fuller, C. A.

1985-01-01

The feeding behavior of two squirrel monkeys flown in Spacelab 3 is compared to that of six monkeys exposed to 1.5 G through centrifugation. The monkeys in the centrifugation study were housed unrestrained in cages, maintained at 25 C + or - 1 C, exposed to a 12:12 light/dark cycle, and had unrestrained access to food and water. The Spacelab monkeys were maintained at 26 C, exposed to a 12:12 light/dark cycle and had unlimited food and water. It is observed that the centrifuge rats displayed a change in feeding behavior for 4 days prior to resuming a normal pattern; one Spacelab monkey exhibited a 6 day depression before recover to control levels, and the feeding pattern of the second monkey was not influenced by the environment. It is noted that the effect of an altered dynamic environment is variable on the feeding behavior of individual monkeys.

A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys.

PubMed

Kachura, Melissa A; Hickle, Colin; Kell, Sariah A; Sathe, Atul; Calacsan, Carlo; Kiwan, Radwan; Hall, Brian; Milley, Robert; Ott, Gary; Coffman, Robert L; Kanzler, Holger; Campbell, John D

2016-01-01

Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important. Copyright © 2015 by The American Association of Immunologists, Inc.

Effects of chair restraint on the strength of the tibia in rhesus monkeys

NASA Technical Reports Server (NTRS)

Hutchinson, T. M.; Bakulin, A. V.; Rakhmanov, A. S.; Martin, R. B.; Steele, C. R.; Arnaud, S. B.

2001-01-01

To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post-mortem (r2 = 0.95, P < 0.0001). Inter-test precision was 4.28+/-1.4%. Normative data in 24 monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/-1.6 Nm2, P < 0.05). Five monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2-week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.

Human neural stem cells survive long term in the midbrain of dopamine-depleted monkeys after GDNF overexpression and project neurites toward an appropriate target.

PubMed

Wakeman, Dustin R; Redmond, D Eugene; Dodiya, Hemraj B; Sladek, John R; Leranth, Csaba; Teng, Yang D; Samulski, R Jude; Snyder, Evan Y

2014-06-01

Transplanted multipotent human fetal neural stem cells (hfNSCs) significantly improved the function of parkinsonian monkeys in a prior study primarily by neuroprotection, with only 3%-5% of cells expressing a dopamine (DA) phenotype. In this paper, we sought to determine whether further manipulation of the neural microenvironment by overexpression of a developmentally critical molecule, glial cell-derived neurotrophic factor (GDNF), in the host striatum could enhance DA differentiation of hfNSCs injected into the substantia nigra and elicit growth of their axons to the GDNF-expressing target. hfNSCs were transplanted into the midbrain of 10 green monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine. GDNF was delivered concomitantly to the striatum via an adeno-associated virus serotype 5 vector, and the fate of grafted cells was assessed after 11 months. Donor cells remained predominantly within the midbrain at the injection site and sprouted numerous neurofilament-immunoreactive fibers that appeared to course rostrally toward the striatum in parallel with tyrosine hydroxylase-immunoreactive fibers from the host substantia nigra but did not mature into DA neurons. This work suggests that hfNSCs can generate neurons that project long fibers in the adult primate brain. However, in the absence of region-specific signals and despite GDNF overexpression, hfNSCs did not differentiate into mature DA neurons in large numbers. It is encouraging, however, that the adult primate brain appeared to retain axonal guidance cues. We believe that transplantation of stem cells, specifically instructed ex vivo to yield DA neurons, could lead to reconstruction of some portion of the nigrostriatal pathway and prove beneficial for the parkinsonian condition. ©AlphaMed Press.

Outbreak of pasteurellosis in captive Bolivian squirrel monkeys (Saimiri boliviensis)

PubMed Central

YOSHINO, Mizuki; SASAKI, Jun; KURAMOCHI, Konomi; IKEZAWA, Mitsutaka; MUKAIZAWA, Natsuko; GORYO, Masanobu

2017-01-01

In September 2012, five Bolivian squirrel monkeys housed in a zoological park died within sequential several days without obvious clinical signs. In a necrospy, one monkey presented swelling of the kidney with multifocal white nodules in the parenchyma, and other two had pulmonary congestion. Histopathologically, multifocal bacterial colonies of gram-negative coccobacillus were found in the sinusoid of the liver in all monkeys examined (Nos.1−4). Additionally, purulent pyelonephritis, pneumonia and disseminated small bacterial colonies in blood vessels were observed. Immunohistochemically, the bacterial colonies from two monkeys were positive for P. multocida capsular serotype D. Based on these findings, these monkeys were diagnosed as septicemia caused by acute P. multocida infection. PMID:28190821

Outbreak of pasteurellosis in captive Bolivian squirrel monkeys (Saimiri boliviensis).

PubMed

Yoshino, Mizuki; Sasaki, Jun; Kuramochi, Konomi; Ikezawa, Mitsutaka; Mukaizawa, Natsuko; Goryo, Masanobu

2017-03-23

In September 2012, five Bolivian squirrel monkeys housed in a zoological park died within sequential several days without obvious clinical signs. In a necrospy, one monkey presented swelling of the kidney with multifocal white nodules in the parenchyma, and other two had pulmonary congestion. Histopathologically, multifocal bacterial colonies of gram-negative coccobacillus were found in the sinusoid of the liver in all monkeys examined (Nos.1-4). Additionally, purulent pyelonephritis, pneumonia and disseminated small bacterial colonies in blood vessels were observed. Immunohistochemically, the bacterial colonies from two monkeys were positive for P. multocida capsular serotype D. Based on these findings, these monkeys were diagnosed as septicemia caused by acute P. multocida infection.

Extracellular biosynthesis of CdTe quantum dots by the fungus Fusarium oxysporum and their anti-bacterial activity

NASA Astrophysics Data System (ADS)

Syed, Asad; Ahmad, Absar

2013-04-01

The growing demand for semiconductor [quantum dots (Q-dots)] nanoparticles has fuelled significant research in developing strategies for their synthesis and characterization. They are extensively investigated by the chemical route; on the other hand, use of microbial sources for biosynthesis witnessed the highly stable, water dispersible nanoparticles formation. Here we report, for the first time, an efficient fungal-mediated synthesis of highly fluorescent CdTe quantum dots at ambient conditions by the fungus Fusarium oxysporum when reacted with a mixture of CdCl2 and TeCl4. Characterization of these biosynthesized nanoparticles was carried out by different techniques such as Ultraviolet-visible (UV-Vis) spectroscopy, Photoluminescence (PL), X-ray Diffraction (XRD), X-ray Photoelectron spectroscopy (XPS), Transmission Electron Microscopy (TEM) and Fourier Transformed Infrared Spectroscopy (FTIR) analysis. CdTe nanoparticles shows antibacterial activity against Gram positive and Gram negative bacteria. The fungal based fabrication provides an economical, green chemistry approach for production of highly fluorescent CdTe quantum dots.

Curing Color Blindness—Mice and Nonhuman Primates

PubMed Central

Neitz, Maureen; Neitz, Jay

2014-01-01

It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. PMID:25147187

Curing color blindness--mice and nonhuman primates.

PubMed

Neitz, Maureen; Neitz, Jay

2014-08-21

It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Cytotoxic T lymphocyte antigen 4 decreases humoral and cellular immunity by adenovirus to enhance target GFP gene transfer in C57BL/6 mice.

PubMed

Bai, Dou; Zhu, Wei; Zhang, Yu; Long, Ling; Zhu, Naishuo

2015-01-01

Adenoviruses (Ad) are once potential and promising vectors for gene delivery, but the immunogenicity attenuates its transfer efficiency. Cytotoxic T lymphocyte antigen 4 (CTLA-4) can inhibit T cell immunity. Thus, we aimed to study the effect of CTLA-4 in the process of Ad-mediated gene transfer. The C57BL/6 mice were injected by Ad vectors at twice, and CTLA-4 was administrated after the first Ad injection. Then, the CD3(+)CD4(+) T cells and circulating levels of IL-2, IL-4, and anti-Ad IgG were decreased by CTLA-4, while Ad generated immune responses. The green fluorescence protein (GFP) expressions of tissues were enhanced by CTLA-4 till injection of Ad at twice. Our results indicate that CTLA-4 can inhibit humoral and cellular immunity by adenovirus generation to enhance GFP delivery, and provide a potential way to assist in Ad-mediated gene transfer.

Aged monkeys as a partial model for Parkinson's disease.

PubMed

Hurley, P J; Elsworth, J D; Whittaker, M C; Roth, R H; Redmond, D E

2011-09-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. Copyright © 2011 Elsevier Inc. All rights reserved.

Aged monkeys as a partial model for Parkinson's disease

PubMed Central

Hurley, P.J.; Elsworth, J.D.; Whittaker, M.C.; Roth, R.H.; Redmond, D.E.

2011-01-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, eating problems, delayed initiation of movement, and poverty of movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. PMID:21620883

Steroidal and nonsteroidal antiinflammatory medications can improve photoreceptor survival after laser retinal photocoagulation.

PubMed

Brown, Jeremiah; Hacker, Henry; Schuschereba, Steven T; Zwick, Harry; Lund, David J; Stuck, Bruce E

2007-10-01

To determine whether methylprednisolone or indomethacin can enhance photoreceptor survival after laser retinal injury in an animal model. Experimental study. Twenty rhesus monkeys. Twenty rhesus monkeys (Macaca mulatta) received a grid of argon green (514.5 nm, 10 ms) laser lesions in the macula of the right eye and a grid of neodymium:yttrium-aluminum-garnet (Nd:YAG; 1064 nm, 10 ns) lesions in the macula of the left eye, followed by randomization to 2 weeks of treatment in 1 of 4 treatment groups: high-dose methylprednisolone, moderate-dose methylprednisolone, indomethacin, or control. The lesions were assessed at day 1, day 14, 2 months, and 4 months. The authors were masked to the treatment group. This report discusses the histologic results of ocular tissue harvested at 4 months. The number of surviving photoreceptor cell nuclei within each lesion was compared with the number of photoreceptor nuclei in surrounding unaffected retina. The proportion of surviving photoreceptor nuclei was compared between each treatment group. Argon retinal lesions in the high-dose steroid treatment group and the indomethacin treatment group demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Hemorrhagic Nd:YAG lesions demonstrated improved survivability with indomethacin treatment compared with controls (P = 0.003). In nonhemorrhagic Nd:YAG laser retinal lesions, the lesions treated with moderate-dose steroids demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Based on histologic samples of retinal laser lesions 4 months after injury, treatment with indomethacin resulted in improved photoreceptor survival in argon laser lesions and hemorrhagic Nd:YAG laser lesions. Treatment with systemic methylprednisolone demonstrated improved photoreceptor survival in argon retinal lesions and in nonhemorrhagic Nd:YAG lesions.

Increased biomass and quality and reduced heavy metal accumulation of edible tissues of vegetables in the presence of Cd-tolerant and immobilizing Bacillus megaterium H3.

PubMed

Wang, Qi; Zhang, Wen-Ji; He, Lin-Yan; Sheng, Xia-Fang

2018-02-01

A Cd-resistant and immobilizing Bacillus megaterium H3 was characterized for its impact on the biomass and quality and heavy metal uptake of edible tissues of two vegetables (Brassica campestris L. var. Aijiaohuang and Brassica rapa L. var. Shanghaiqing) grown in heavy metal-polluted soil. The impact of strain H3 on the soil quality was also evaluated. The increase in the edible tissue biomass and the contents of soluble proteins and vitamin C of the vegetables inoculated with strain H3 ranged from 18% to 33%, 17% to 31%, and 15% to 19%, respectively, compared with the controls. Strain H3 significantly decreased the edible tissue Cd and Pb contents of the two greens (41-80%), DTPA-extractable Cd content (35-47%) of the rhizosphere soils, and Cd and Pb translocation factors (25-56%) of the greens compared with the controls. Moreover, strain H3 significantly increased the organic matter content (17-21%) and invertase activity (13-14%) of the rhizosphere soils compared with the controls. Our results demonstrated the increased edible tissue biomass and quality, decreased Cd and Pb uptake of the edible tissues, and improved soil quality in the presence of strain H3. The results also suggested an effective bacterial-enhanced technique for decreased metal uptake of greens and improved vegetable and soil qualities in the metal-contaminated soils. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of clofibrate and indocyanine green on the hepatobiliary disposition of acetaminophen and its metabolites in male CD-1 mice.

PubMed

Chen, C; Hennig, G E; McCann, D J; Manautou, J E

2000-11-01

1. The effects of clofibrate (CFB) and indocyanine green (ICG) on the biliary excretion of acetaminophen (APAP) and its metabolites were investigated. 2. Male CD-1 mice were pretreated with 500 mg CFB/kg, i.p. for 10 days. Controls received corn oil vehicle only. After overnight fasting, common bile duct-cannulated mice were challenged with a non-toxic dose of APAP (1 mmol/kg, i.v.). 3. CFB pretreatment did not affect bile flow rate, nor did it affect the cumulative biliary excretion of APAP and its conjugated metabolites. 4. Additional CFB or corn oil pretreated mice were given 30 mumol indocyanine green (ICG)/kg, i.v., immediately before APAP dosing. ICG is a non-metabolizable organic anion that is completely excreted into the bile through a canalicular transport process for organic anions. 5. ICG significantly decreased the bile flow rate and biliary concentration of APAP-glutathione, APAP-glucuronide and APAP-mercapturate within the first hour after dosing without affecting the biliary concentration of APAP. 6. The results indicate that CFB pretreatment does not affect the total amount of APAP and its metabolites excreted in bile. They also suggest that the biliary excretion of several conjugated metabolites of APAP share the same excretory pathway with the organic anion ICG.

Selective induction of cell-mediated immunity and protection of rhesus macaques from chronic SHIV{sub KU2} infection by prophylactic vaccination with a conserved HIV-1 envelope peptide-cocktail

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nehete, Pramod N.; Nehete, Bharti P.; Hill, Lori

2008-01-05

Infection of Indian-origin rhesus macaques by the simian human immunodeficiency virus (SHIV) is considered to be a suitable preclinical model for directly testing efficacy of vaccine candidates based on the HIV-1 envelope. We used this model for prophylactic vaccination with a peptide-cocktail comprised of highly conserved HIV-1 envelope sequences immunogenic/antigenic in macaques and humans. Separate groups of macaques were immunized with the peptide-cocktail by intravenous and subcutaneous routes using autologous dendritic cells (DC) and Freund's adjuvant, respectively. The vaccine elicited antigen specific IFN-{gamma}-producing cells and T-cell proliferation, but not HIV-neutralizing antibodies. The vaccinated animals also exhibited efficient cross-clade cytolytic activitymore » against target cells expressing envelope proteins corresponding to HIV-1 strains representative of multiple clades that increased after intravenous challenge with pathogenic SHIV{sub KU2}. Virus-neutralizing antibodies were either undetectable or present only transiently at low levels in the control as well as vaccinated monkeys after infection. Significant control of plasma viremia leading to undetectable levels was achieved in majority of vaccinated monkeys compared to mock-vaccinated controls. Monkeys vaccinated with the peptide-cocktail using autologous DC, compared to Freund's adjuvant, and the mock-vaccinated animals, showed significantly higher IFN-{gamma} production, higher levels of vaccine-specific IFN-{gamma} producing CD4{sup +} cells and significant control of plasma viremia. These results support DC-based vaccine delivery and the utility of the conserved HIV-1 envelope peptide-cocktail, capable of priming strong cell-mediated immunity, for potential inclusion in HIV vaccination strategies.« less

4-1BB and CD28 Signaling Plays a Synergistic Role in Redirecting Umbilical Cord Blood T Cells Against B-Cell Malignancies

PubMed Central

Tammana, Syam; Huang, Xin; Wong, Marianna; Milone, Michael C.; Ma, Linan; Levine, Bruce L.; June, Carl H.; Wagner, John E.; Blazar, Bruce R.

2010-01-01

Abstract Umbilical cord blood (UCB) T cells can be redirected to kill leukemia and lymphoma cells by engineering with a single-chain chimeric antigen receptor (CAR) and thus may have general applications in adoptive cell therapy. However, the role of costimulatory molecules in UCB T-cell activation and effector functions in context with CAR remains elusive. To investigate the effect of costimulatory molecules (4-1BB and CD28) on UCB T cells, we transduced UCB T cells with lentiviral vectors expressing Green Fluorescent Protein (GFP) and CAR for CD19 containing an intracellular domain of the CD3ζ chain and either a 4-1BB (UCB-19BBζ) or a CD28 intracellular domain (UCB-1928ζ), both (UCB-1928BBζ), or neither (UCB-19ζ). We found that UCB-19BBζ and UCB-28BBζ T cells exhibited more cytotoxicity to CD19+ leukemia and lymphoma cell lines than UCB-19ζ and UCB-1928ζ, although differences in secretion of interleukin-2 and interferon-γ by these T cells were not evident. In vivo adoptive transfer of these T cells into intraperitoneal tumor-bearing mice demonstrated that UCB-19BBζ and UCB-1928BBζ T cells mounted the most potent antitumor response. The mice adoptively transferred with UCB-1928BBζ cells survived longer than the mice with UCB-19BBζ. Moreover, UCB-1928BBζ T cells mounted a more robust antitumor response than UCB-19BBζ in a systemic tumor model. Our data suggest a synergistic role of 4-1BB and CD28 costimulation in engineering antileukemia UCB effector cells and implicate a design for redirected UCB T-cell therapy for refractory leukemia. PMID:19719389

Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer.

PubMed

Liu, Zhen; Cai, Yijun; Wang, Yan; Nie, Yanhong; Zhang, Chenchen; Xu, Yuting; Zhang, Xiaotong; Lu, Yong; Wang, Zhanyang; Poo, Muming; Sun, Qiang

2018-02-08

Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys. For SCNT using fetal monkey fibroblasts, 6 pregnancies were confirmed in 21 surrogates and yielded 2 healthy babies. For SCNT using adult monkey cumulus cells, 22 pregnancies were confirmed in 42 surrogates and yielded 2 babies that were short-lived. In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma.

PubMed

Polson, A G; Williams, M; Gray, A M; Fuji, R N; Poon, K A; McBride, J; Raab, H; Januario, T; Go, M; Lau, J; Yu, S-F; Du, C; Fuh, F; Tan, C; Wu, Y; Liang, W-C; Prabhu, S; Stephan, J-P; Hongo, J-A; Dere, R C; Deng, R; Cullen, M; de Tute, R; Bennett, F; Rawstron, A; Jack, A; Ebens, A

2010-09-01

Antibody-drug conjugates (ADCs) are potent cytotoxic drugs linked to antibodies through chemical linkers, and allow specific targeting of drugs to neoplastic cells. The expression of CD22 is limited to B-cells, and we show that CD22 is expressed on the vast majority of non-Hodgkin's lymphomas (NHLs). An ideal target for an ADC for the treatment of NHL would have limited expression outside the B-cell compartment and be highly effective against NHL. We generated an ADC consisting of a humanized anti-CD22 antibody conjugated to the anti-mitotic agent maytansine with a stable linker (anti-CD22-MCC-DM1). Anti-CD22-MCC-DM1 was broadly effective in in vitro killing assays on NHL B-cell lines. We did not find a strong correlation between in vitro potency and CD22 surface expression, internalization of ADC or sensitivity to free drug. We show that anti-CD22-MCC-DM1 was capable of inducing complete tumor regression in NHL xenograft mouse models. Further, anti-CD22-MCC-DM1 was well tolerated in cynomolgus monkeys and substantially decreased circulating B-cells as well as follicle size and germinal center formation in lymphoid organs. These results suggest that anti-CD22-MCC-DM1 has an efficacy, safety and pharmacodynamic profile that support its use as a treatment for NHL.

Herbal Compound Songyou Yin and Moderate Swimming Suppress Growth and Metastasis of Liver Cancer by Enhancing Immune Function.

PubMed

Zhang, Quan-Bao; Meng, Xiang-Ting; Jia, Qing-An; Bu, Yang; Ren, Zheng-Gang; Zhang, Bo-Heng; Tang, Zhao-You

2016-09-01

Objective Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity. © The Author(s) 2015.

The neonatal marmoset monkey ovary is very primitive exhibiting many oogonia

PubMed Central

Fereydouni, B; Drummer, C; Aeckerle, N; Schlatt, S; Behr, R

2014-01-01

Oogonia are characterized by diploidy and mitotic proliferation. Human and mouse oogonia express several factors such as OCT4, which are characteristic of pluripotent cells. In human, almost all oogonia enter meiosis between weeks 9 and 22 of prenatal development or undergo mitotic arrest and subsequent elimination from the ovary. As a consequence, neonatal human ovaries generally lack oogonia. The same was found in neonatal ovaries of the rhesus monkey, a representative of the old world monkeys (Catarrhini). By contrast, proliferating oogonia were found in adult prosimians (now called Strepsirrhini), which is a group of ‘lower’ primates. The common marmoset monkey (Callithrix jacchus) belongs to the new world monkeys (Platyrrhini) and is increasingly used in reproductive biology and stem cell research. However, ovarian development in the marmoset monkey has not been widely investigated. Herein, we show that the neonatal marmoset ovary has an extremely immature histological appearance compared with the human ovary. It contains numerous oogonia expressing the pluripotency factors OCT4A, SALL4, and LIN28A (LIN28). The pluripotency factor-positive germ cells also express the proliferation marker MKI67 (Ki-67), which has previously been shown in the human ovary to be restricted to premeiotic germ cells. Together, the data demonstrate the primitiveness of the neonatal marmoset ovary compared with human. This study may introduce the marmoset monkey as a non-human primate model to experimentally study the aspects of primate primitive gonad development, follicle assembly, and germ cell biology in vivo. PMID:24840529

Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

PubMed

Czoty, Paul W; Nader, Michael A

2015-03-13

Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections.

PubMed

Fura, Aberra; Khanna, Ashish; Vyas, Viral; Koplowitz, Barry; Chang, Shu-Ying; Caporuscio, Christian; Boulton, David W; Christopher, Lisa J; Chadwick, Kristina D; Hamann, Lawrence G; Humphreys, W Griffith; Kirby, Mark

2009-06-01

Saxagliptin is a potent, selective, reversible dipeptidyl peptidase 4 (DPP4) inhibitor specifically designed for extended inhibition of the DPP4 enzyme and is currently under development for the treatment of type-2 diabetes. The pharmacokinetics of saxagliptin were evaluated in rats, dogs, and monkeys and used to predict its human pharmacokinetics. Saxagliptin was rapidly absorbed and had good bioavailability (50-75%) in the species tested. The plasma clearance of saxagliptin was higher in rats (115 ml/min/kg) than in dogs (9.3 ml/min/kg) and monkeys (14.5 ml/min/kg) and was predicted to be low to moderate in humans. The plasma elimination half-life was between 2.1 and 4.4 h in rats, dogs, and monkeys, and both metabolism and renal excretion contributed to the overall elimination. The primary metabolic clearance pathway involved the formation of a significant circulating, pharmacologically active hydroxylated metabolite, M2. The volume of distribution values observed in rats, dogs, and monkeys (1.3-5.2 l/kg) and predicted for humans (2.7 l/kg) were greater than those for total body water, indicating extravascular distribution. The in vitro serum protein binding was low (< or =30%) in rats, dogs, monkeys, and humans. After intra-arterial administration of saxagliptin to Sprague-Dawley and Zucker diabetic fatty rats, higher levels of saxagliptin and M2 were observed in the intestine (a proposed major site of drug action) relative to that in plasma. Saxagliptin has prolonged pharmacodynamic properties relative to its plasma pharmacokinetic profile, presumably due to additional contributions from M2, distribution of saxagliptin and M2 to the intestinal tissue, and prolonged dissociation of both saxagliptin and M2 from DPP4.

Organic electronic devices via interface engineering

NASA Astrophysics Data System (ADS)

Xu, Qianfei

This dissertation focuses on interface engineering and its influence on organic electronic devices. A comprehensive review of interface studies in organic electronic devices is presented in Chapter 1. By interface engineering at the cathode contact, an ultra-high efficiency green polymer light emitting diode is demonstrated in Chapter 2. The interface modification turns out to be solution processable by using calcium acetylacetonate, donated by Ca(acac)2. The device structure is Induim Tin Oxide (ITO)/3,4-polyethylenedioxythiophene-polystyrene-sulfonate (PEDOT)/Green polyfluorene/Ca(acac) 2/Al. Based on this structure, we obtained device efficiencies as high as 28 cd/A at 2650 cd/m2, which is about a 3 times improvement over previous devices. The mechanism of this nano-layer has been studied by I-L-V measurements, photovoltaic measurements, XPS/UPS studies, impedance measurements as well as transient EL studies. The interfacial layer plays a crucial role for the efficiency improvement. It is believed to work as a hole blocking layer as well as an electron injection layer. Meanwhile, a systematic study on ITO electrodes is also carried out in Chapter 4. By engineering the interface at ITO electrode, the device lifetime has been improved. In Chapter 5, very bright white emission PLEDs are fabricated based on blue polyfluorene (PF) doped with 1 wt% 6, 8, 15, 17-tetraphyenyl-1.18, 4.5, 9.10, 13.14-tetrabenzoheptacene (TBH). The maximum luminance exceeds 20,000 cd/m2. The maximum luminance efficiency is 3.55 cd/A at 4228 cd/m2 while the maximum power efficiency is 1.6 lm/W at 310 cd/m2. The white color is achieved by an incomplete energy transfer from blue PF to TBH. The devices show super stable CIE coordinates as a function of current density. The interface engineering is also applied to memory devices. In Chapter 6, a novel nonvolatile memory device is fabricated by inserting a buffer layer at the anode contact. Devices with the structure of Cu/Buffer-layer/organic layer/Cu show very attractive electrical bi-stability. The switching mechanism is believed to origin from by the different copper ion concentrations in the organic layer. This opens up a promising way to achieve high-performance organic electronic devices.

Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

PubMed

Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

2014-12-01

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

Strict tropism for CD71+/CD234+ human reticulocytes limits the zoonotic potential of Plasmodium cynomolgi

PubMed Central

Kosaisavee, Varakorn; Suwanarusk, Rossarin; Chua, Adeline C. Y.; Kyle, Dennis E.; Malleret, Benoit; Zhang, Rou; Imwong, Mallika; Imerbsin, Rawiwan; Ubalee, Ratawan; Sámano-Sánchez, Hugo; Yeung, Bryan K. S.; Ong, Jessica J. Y.; Lombardini, Eric; Nosten, François; Tan, Kevin S. W.; Bifani, Pablo; Snounou, Georges; Rénia, Laurent

2017-01-01

Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi–infected human reticulocytes that are strikingly similar to those observed for P vivax. These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria. PMID:28698207

Low driving voltage blue, green, yellow, red and white organic light-emitting diodes with a simply double light-emitting structure.

PubMed

Zhang, Zhensong; Yue, Shouzhen; Wu, Yukun; Yan, Pingrui; Wu, Qingyang; Qu, Dalong; Liu, Shiyong; Zhao, Yi

2014-01-27

Low driving voltage blue, green, yellow, red and white phosphorescent organic light-emitting diodes (OLEDs) with a common simply double emitting layer (D-EML) structure are investigated. Our OLEDs without any out-coupling schemes as well as n-doping strategies show low driving voltage, e.g. < 2.4 V for onset and < 3 V for 1000 cd/m2, and high efficiency of 32.5 lm/W (13.3%), 58.8 lm/W (14.3%), 55.1 lm/W (14.6%), 24.9 lm/W (13.7%) and 45.1 lm/W (13.5%) for blue, green, yellow, red and white OLED, respectively. This work demonstrates that the low driving voltages and high efficiencies can be simultaneously realized with a common simply D-EML structure.

Energy metabolism of Macaca mulatta during spaceflight

NASA Technical Reports Server (NTRS)

Hoban-Higgins, T. M.; Stein, T. P.; Dotsenko, M. A.; Korolkov, V. I.; Fuller, C. A.

2000-01-01

The mean daily energy expenditure rates of two rhesus monkeys (Macaca mulatta) were determined during spaceflight on the joint U.S./Russian Bion 11 mission by the doubly labeled water (DLW, 2H218O) method. Control values were obtained from two studies performed under flight-like conditions (n = 4). The mean inflight energy expenditure for the two Bion 11 monkeys was 81.3 kcal/kg/day, which was higher than that seen previously. The average energy expenditure (77.6 +/- 4.4 kcal/kg/day) for the four ground control monkeys was slightly lower than had been measured previously.

Laser Raman Spectroscopy of Ultraviolet-Induced Cataracts in Rabbits and Monkeys.

DTIC Science & Technology

1979-12-01

ILTRAVIOLETINHUCED CATARACTS SIN RABBITS AND MONKEYS Dwaine M. Thomas, Ph.D. ,KennethL. Schepler, Captain, USAF December 1979 Final Report for Period...3AMAN VECTROSCOPY OF .JLTRAV IOLET;NDUCED) POR U77 -FbR7 WATARACTS IN RABBITS AND MONKEYS .0 R. O,;4MIE V 111___ 2= _ 7. AUTHOR(*) S. CONTRACT OR GRANT...cataracts ABSTRACT (Continue on rev’erse side if necessary art# identify hV block numb~er) he Raman spectrl .of aormal rabbit’ana monkey lenses have been

Synthesis of Novel Sea-Urchin-Like CdS and Their Optical Properties.

PubMed

Kamran, Muhammad Arshad; Liu, Ruibin; Shi, Li-Jie; Bukhtiar, Arfan; Li, Jing; Zou, Bingsuo

2015-06-01

A novel morphology of CdS sea-urchin-like microstructures is synthesized by simple thermal evaporation process. Microstructures with average size of 20-50 μm are composed of single crystalline CdS nanobelts. The structural, compositional, morphological characterization of the product were examined by X-ray diffraction, energy dispersive X-ray spectroscopy, Raman spectroscopy, scanning electron microscope, transmission electron microscopy and selected area electron diffraction while optical properties are investigated by Photoluminescence spectroscopy and time-resolved Photoluminescence measurements. The tentative growth mechanism for the growth of sea-urchin-like CdS is proposed and described briefly. A strong green emission with a maximum around 517 nm was observed from the individual CdS microstructure at room temperature, which was attributed to band-edge emission of CdS. These Novel structures exhibit excellent lasing (stimulated emission) with low threshold (9.07 μJ cm(-2)) at room temperature. We analyze the physical mechanism of stimulated emission. These results are important in the design of green luminescence, low-threshold laser and display devices in the future.

A comparative analysis of green synthesis approach starch capped metal oxides (ZnO & CdO) nanoparticles and its bacterial activity

NASA Astrophysics Data System (ADS)

Vidhya, K.; Devarajan, V. P.; Viswanathan, C.; Nataraj, D.; Bhoopathi, G.

2013-06-01

In this study, we have investigated the bacterial activity of starch capped ZnO & CdO NPs. The NPs were prepared through green technique under room temperature and then obtained samples were characterized by using XRD and PL techniques. XRD pattern confirms the crystal nature it shows hexagonal structure for ZnO NPs and monoclinic structure for CdO NPs and their average particle size is ±20 nm. Further, the optical properties of NPs were investigated using PL technique in which the starch capped ZnO NPs shows maximum emission at 440 nm whereas starch capped CdO NPs shows maximum emission at 545 nm. Finally, toxic test was performed with E.coli bacteria and their results were investigated. Hence, starch capped ZnO NPs induced less killing effect when compared with starch capped CdO NPs. Therefore, we conclude that the starch capped ZnO NPs may be less toxic to microorganisms when compared with starch capped CdO NPs. In addition, starch capped ZnO NPs is also suitable for anti-microbial activity.

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

NASA Astrophysics Data System (ADS)

Mishra, Nimai; Orfield, Noah J.; Wang, Feng; Hu, Zhongjian; Krishnamurthy, Sachidananda; Malko, Anton V.; Casson, Joanna L.; Htoon, Han; Sykora, Milan; Hollingsworth, Jennifer A.

2017-05-01

Semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters--arm length and arm diameter, respectively--but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission.

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

PubMed Central

Mishra, Nimai; Orfield, Noah J.; Wang, Feng; Hu, Zhongjian; Krishnamurthy, Sachidananda; Malko, Anton V.; Casson, Joanna L.; Htoon, Han; Sykora, Milan; Hollingsworth, Jennifer A.

2017-01-01

Semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters—arm length and arm diameter, respectively—but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission. PMID:28497776

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

DOE PAGES

Mishra, Nimai; Orfield, Noah Jeremiah; Wang, Feng; ...

2017-05-12

Here, semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters—arm length and armmore » diameter, respectively—but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission.« less

Using shape to turn off blinking for two-colour multiexciton emission in CdSe/CdS tetrapods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mishra, Nimai; Orfield, Noah Jeremiah; Wang, Feng

Here, semiconductor nanostructures capable of emitting from two excited states and thereby of producing two photoluminescence colours are of fundamental and potential technological significance. In this limited class of nanocrystals, CdSe/CdS core/arm tetrapods exhibit the unusual trait of two-colour (red and green) multiexcitonic emission, with green emission from the CdS arms emerging only at high excitation fluences. Here we show that by synthetic shape-tuning, both this multi-colour emission process, and blinking and photobleaching behaviours of single tetrapods can be controlled. Specifically, we find that the properties of dual emission and single-nanostructure photostability depend on different structural parameters—arm length and armmore » diameter, respectively—but that both properties can be realized in the same nanostructure. Furthermore, based on results of correlated photoluminescence and transient absorption measurements, we conclude that hole-trap filling in the arms and partial state-filling in the core are necessary preconditions for the observation of multiexciton multi-colour emission.« less

Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.

PubMed

Feng, Na; Liu, Yuxiu; Wang, Jianzhong; Xu, Weiwei; Li, Tiansong; Wang, Tiecheng; Wang, Lei; Yu, Yicong; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Gao, Yuwei; Hu, Guixue; Xia, Xianzhu

2016-08-02

In 2008, an outbreak of canine distemper virus (CDV) infection in monkeys was reported in China. We isolated CDV strain (subsequently named Monkey-BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM receptors from dog, monkey and human origin, and analyzed the H gene of Monkey-BJ01-DV with other strains. The Monkey-BJ01-DV isolate replicated to the highest titer on Vero cells expressing dog-origin SLAM (10(5.2±0.2) TCID50/ml) and monkey-origin SLAM (10(5.4±0.1) TCID50/ml), but achieved markedly lower titers on human-origin SLAM cells (10(3.3±0.3) TCID50/ml). Phylogenetic analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related to other CDV strains obtained during recent CDV epidemics among species of the Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV, Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V, Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other animals at the same period. Our results suggested that the monkey origin-CDV-H protein could possess specific substitutions to adapt to the new host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect and replicate in host cells, but further adaptation may be required for efficient replication in host cells expressing the human SLAM receptor.

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells.

PubMed

Chen, Jie; Pan, Yuqin; He, Bangshun; Ying, Houqun; Wang, Feng; Sun, Huiling; Deng, Qiwen; Liu, Xian; Lin, Kang; Peng, Hongxin; Cho, William C; Wang, Shukui

2015-10-01

The association between CD147 and cancer stem cells (CSCs) provides a new angle for cancer treatments. The aim of this study was to investigate the biological roles of CD147 in colorectal CSCs. The Oct4-green fluorescent protein (GFP) vector was used to isolate CSCs and pYr-mir30-shRNA was used to generate short hairpin RNA (shRNA) specifically for CD147. After RNA interference (RNAi), CD147 was evaluated by reverse transcription‑quantitative PCR and western blot analysis, and its biological functions were assessed by MTT and invasion assays. The results showed that the differentiation of isolated CSC-like HT-29 cells was blocked and these cells were highly positive for CD44 and CD147. RNAi-mediated CD147 silencing reduced the expression of CD147 at both mRNA and protein levels. Moreover, the activities of proliferation and invasion were decreased obviously in CSCs. Knockdown of CD147 increased the chemosensitivity of CSC-like cells to gemcitabine, cisplatin, docetaxel at 0.1, 1 and 10 µM respectively, however, there was no significant difference among the three groups to paclitaxel at 10 µM. In conclusion, these results suggest that CD147 plays an important role in colorectal CSCs and might be regarded as a novel CSC-specific targeted strategy against colorectal cancer.

A survey for Cyclospora spp. in Kenyan primates, with some notes on its biology.

PubMed

Eberhard, M L; Njenga, M N; DaSilva, A J; Owino, D; Nace, E K; Won, K Y; Mwenda, J M

2001-12-01

From March 1999 through August 2000, 511 stool samples collected from 11 different primate species in 10 geographically distinct locations in Kenya, East Africa, were screened for the presence of Cyclospora spp. oocysts. Positive samples (43/102, 42%) were identified in vervet monkeys (Cercopithecus aethiops) in 4 of 4 locations; 19/206 (9%) in yellow and olive baboons (Papio cynocephalus, P. anubis, respectively) in 5 of 5 locations; and 19/76 (25%) in black and white colobus monkeys (Colobus angolensis, C. guereza, respectively) from 2 of 3 locations. DNA sequences obtained from 18 S rRNA coding regions from respective subsets of these positive samples were typed as Cyclospora cercopitheci (samples from Cercopithecus aethiops). Cyclospora papionis (samples from Papio cynocephalus and P. anubis), and Cyclospora colobi (samples from Colobus angolensis and C. guereza). Cyclospora oocysts were not detected in samples collected from patas, highland sykes, lowland sykes, blue sykes, DeBrazza, or red-tailed monkeys. A coded map showing the geographic location of the collected samples is given. Stool samples from 1 troop of vervet monkeys were collected over a 12-mo period. Positive samples ranged between 21 and 63%. These results suggest that there is no strongly marked seasonality evident in Cyclospora infection in monkeys as has been noted in human infection. This is further confirmed by the recovery of positive samples collected from vervet monkeys, baboons, and colobus monkeys at all times of the year during this survey. This absence of seasonality in infection is especially notable because of the extreme weather patterns typical of Kenya, where marked rainy and dry seasons occur. A second noteworthy observation is that the striking host specificity of the Cyclospora species initially described was confirmed in this survey. Baboons were only infected with C. papionis, vervet monkeys with C. cercopitheci, and colobus monkeys with C. colobi, despite geographic overlaps of both the monkey and parasite species and wide geographic distribution of each parasite and monkey host.

The effects of simultaneous dual focus lenses on refractive development in infant monkeys.

PubMed

Arumugam, Baskar; Hung, Li-Fang; To, Chi-Ho; Holden, Brien; Smith, Earl L

2014-10-16

We investigated the effects of two simultaneously imposed, competing focal planes on refractive development in monkeys. Starting at 3 weeks of age and continuing until 150 ± 4 days of age, rhesus monkeys were reared with binocular dual-focus spectacle lenses. The treatment lenses had central 2-mm zones of zero power and concentric annular zones with alternating powers of +3.0 diopter [D] and plano (pL or 0 D) (n = 7; +3D/pL) or -3.0 D and plano (n = 7; -3D/pL). Retinoscopy, keratometry, and A-scan ultrasonography were performed every 2 weeks throughout the treatment period. For comparison purposes data were obtained from monkeys reared with full field (FF) +3.0 (n = 4) or -3.0 D (n = 5) lenses over both eyes and 33 control animals reared with unrestricted vision. The +3 D/pL lenses slowed eye growth resulting in hyperopic refractive errors that were similar to those produced by FF+3 D lenses (+3 D/pL = +5.25 D, FF +3 D = +4.63 D; P = 0.32), but significantly more hyperopic than those observed in control monkeys (+2.50 D, P = 0.0001). One -3 D/pL monkey developed compensating axial myopia; however, in the other -3 D/pL monkeys refractive development was dominated by the zero-powered portions of the treatment lenses. The refractive errors for the -3 D/pL monkeys were more hyperopic than those in the FF -3 D monkeys (-3 D/pL = +3.13 D, FF -3D = -1.69 D; P = 0.01), but similar to those in control animals (P = 0.15). In the monkeys treated with dual-focus lenses, refractive development was dominated by the more anterior (i.e., relatively myopic) image plane. The results indicate that imposing relative myopic defocus over a large proportion of the retina is an effective means for slowing ocular growth. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

The Effects of Simultaneous Dual Focus Lenses on Refractive Development in Infant Monkeys

PubMed Central

Arumugam, Baskar; Hung, Li-Fang; To, Chi-ho; Holden, Brien; Smith, Earl L.

2014-01-01

Purpose. We investigated the effects of two simultaneously imposed, competing focal planes on refractive development in monkeys. Methods. Starting at 3 weeks of age and continuing until 150 ± 4 days of age, rhesus monkeys were reared with binocular dual-focus spectacle lenses. The treatment lenses had central 2-mm zones of zero power and concentric annular zones with alternating powers of +3.0 diopter [D] and plano (pL or 0 D) (n = 7; +3D/pL) or −3.0 D and plano (n = 7; −3D/pL). Retinoscopy, keratometry, and A-scan ultrasonography were performed every 2 weeks throughout the treatment period. For comparison purposes data were obtained from monkeys reared with full field (FF) +3.0 (n = 4) or −3.0 D (n = 5) lenses over both eyes and 33 control animals reared with unrestricted vision. Results. The +3 D/pL lenses slowed eye growth resulting in hyperopic refractive errors that were similar to those produced by FF+3 D lenses (+3 D/pL = +5.25 D, FF +3 D = +4.63 D; P = 0.32), but significantly more hyperopic than those observed in control monkeys (+2.50 D, P = 0.0001). One −3 D/pL monkey developed compensating axial myopia; however, in the other −3 D/pL monkeys refractive development was dominated by the zero-powered portions of the treatment lenses. The refractive errors for the −3 D/pL monkeys were more hyperopic than those in the FF −3 D monkeys (−3 D/pL = +3.13 D, FF −3D = −1.69 D; P = 0.01), but similar to those in control animals (P = 0.15). Conclusions. In the monkeys treated with dual-focus lenses, refractive development was dominated by the more anterior (i.e., relatively myopic) image plane. The results indicate that imposing relative myopic defocus over a large proportion of the retina is an effective means for slowing ocular growth. PMID:25324283

Surface states in the photoionization of high-quality CdSe core/shell nanocrystals.

PubMed

Li, Shu; Steigerwald, Michael L; Brus, Louis E

2009-05-26

We use electric force microscopy (EFM) to study single nanocrystal photoionization in two classes of high-quality nanocrystals whose exciton luminescence quantum yields approach unity in solution. The CdSe/CdS/ZnS core/shell nanocrystals do not photoionize, while the CdSe/CdS nanocrystals do show substantial photoionization. This verifies the theoretical prediction that the ZnS shell confines the excited electron within the nanocrystal. Despite the high luminescence quantum yield, photoionization varies substantially among the CdSe/CdS nanocrystals. We have studied the nanocrystal photoionization with both UV (396 nm) and green (532 nm) light, and we have found that the magnitude of the charge due to photoionization per absorbed photon is greater for UV excitation than for green excitation. A fraction of the photoionization occurs directly via a "hot electron" process, using trap states that are either on the particle surface, within the ligand sphere, or within the silicon oxide layer. This must occur without relaxation to the thermalized, lowest-energy, emitting exciton. We discuss the occurrence of hot carrier processes that are common to photoionization, luminescence blinking, and the fast transient optical absorption that is associated with multiple exciton generation MEG studies.

Inhibition of autophagy contributes to the toxicity of cadmium telluride quantum dots in Saccharomyces cerevisiae.

PubMed

Fan, Junpeng; Shao, Ming; Lai, Lu; Liu, Yi; Xie, Zhixiong

2016-01-01

Cadmium telluride quantum dots (CdTe QDs) are used as near-infrared probes in biologic and medical applications, but their cytological effects and mechanism of potential toxicity are still unclear. In this study, we evaluated the toxicity of CdTe QDs of different sizes and investigated their mechanism of toxicity in the yeast Saccharomyces cerevisiae. A growth inhibition assay revealed that orange-emitting CdTe (O-CdTe) QDs (half inhibitory concentration [IC50] =59.44±12.02 nmol/L) were more toxic than green-emitting CdTe QDs (IC50 =186.61±19.74 nmol/L) to S. cerevisiae. Further studies on toxicity mechanisms using a transmission electron microscope and green fluorescent protein tagged Atg8 processing assay revealed that O-CdTe QDs could partially inhibit autophagy at a late stage, which differs from the results reported in mammalian cells. Moreover, autophagy inhibited at a late stage by O-CdTe QDs could be partially recovered by enhancing autophagy with rapamycin (an autophagy activator), combined with an increased number of living cells. These results indicate that inhibition of autophagy acts as a toxicity mechanism of CdTe QDs in S. cerevisiae. This work reports a novel toxicity mechanism of CdTe QDs in yeast and provides valuable information on the effect of CdTe QDs on the processes of living cells.

The therapeutic effect of mesenchymal stem cells on pulmonary myeloid cells following neonatal hyperoxic lung injury in mice.

PubMed

Al-Rubaie, Ali; Wise, Andrea F; Sozo, Foula; De Matteo, Robert; Samuel, Chrishan S; Harding, Richard; Ricardo, Sharon D

2018-06-08

Exposure to high levels of oxygen (hyperoxia) after birth leads to lung injury. Our aims were to investigate the modulation of myeloid cell sub-populations and the reduction of fibrosis in the lungs following administration of human mesenchymal stem cells (hMSC) to neonatal mice exposed to hyperoxia. Newborn mice were exposed to 90% O 2 (hyperoxia) or 21% O 2 (normoxia) from postnatal days 0-4. A sub-group of hyperoxia mice were injected intratracheally with 2.5X10 5 hMSCs. Using flow cytometry we assessed pulmonary immune cells at postnatal days 0, 4, 7 and 14. The following markers were chosen to identify these cells: CD45 + (leukocytes), Ly6C + Ly6G + (granulocytes), CD11b + CD11c + (macrophages); macrophage polarisation was assessed by F4/80 and CD206 expression. hMSCs expressing enhanced green fluorescent protein (eGFP) and firefly luciferase (fluc) were administered via the trachea at day 4. Lung macrophages in all groups were profiled using next generation sequencing (NGS) to assess alterations in macrophage phenotype. Pulmonary collagen deposition and morphometry were assessed at days 14 and 56 respectively. At day 4, hyperoxia increased the number of pulmonary Ly6C + Ly6G + granulocytes and F4/80 low CD206 low macrophages but decreased F4/80 high CD206 high macrophages. At days 7 and 14, hyperoxia increased numbers of CD45 + leukocytes, CD11b + CD11c + alveolar macrophages and F4/80 low CD206 low macrophages but decreased F4/80 high CD206 high macrophages. hMSCs administration ameliorated these effects of hyperoxia, notably reducing numbers of CD11b + CD11c + and F4/80 low CD206 low macrophages; in contrast, F4/80 high CD206 high macrophages were increased. Genes characteristic of anti-inflammatory 'M2' macrophages (Arg1, Stat6, Retnla, Mrc1, Il27ra, Chil3, and Il12b) were up-regulated, and pro-inflammatory 'M1' macrophages (Cd86, Stat1, Socs3, Slamf1, Tnf, Fcgr1, Il12b, Il6, Il1b, and Il27ra) were downregulated in isolated lung macrophages from hyperoxia-exposed mice administered hMSCs, compared to mice without hMSCs. Hydroxyproline assay at day 14 showed that the 2-fold increase in lung collagen following hyperoxia was reduced to control levels in mice administered hMSCs. By day 56 (early adulthood), hMSC administration had attenuated structural changes in hyperoxia-exposed lungs. Our findings suggest that hMSCs reduce neonatal lung injury caused by hyperoxia by modulation of macrophage phenotype. Not only did our cell-based therapy using hMSC induce structural repair, it limited the progression of pulmonary fibrosis.

Defining Tumor Cell and Immune Cell Behavior in Vivo during Pulmonary Metastasis of Breast Cancer

DTIC Science & Technology

2015-09-01

cancer cell extravasation , establishment and growth. PLoS One 4, e6562, doi:10.1371/journal.pone.0006562 (2009). 2 Qian, B. Z. et al. CCL2...cytoplast­ingesting cells behaved with respect to extravasation . We used i.v. injection of labelled anti­CD45 antibody15 to localize ZsGreen+ populations relative...to the vasculature at 4 and 24 h after injection. Consistent with previous data3, non­alveolar macrophages extravasated over this time period (Fig

Electro-active polymers containing pendent 2,7-diarylfluorene fragments as materials for OLEDs

NASA Astrophysics Data System (ADS)

Krucaite, G.; Tavgeniene, D.; Peciulyte, L.; Buika, G.; Liu, L.; Zhang, B.; Xie, Z.; Grigalevicius, S.

2016-05-01

Poly[2-phenyl-7-(4-vinylphenyl)-9,9-diethylfluorene)], poly[2-(1-naphtyl)-7-(4-vinylphenyl)-9,9-diethylfluorene)] and poly[2-(4-biphenyl)-7-(4-vinylphenyl)-9,9-diethylfluorene)] were synthesized and characterized by NMR spectroscopy, elemental analysis and gel permeation chromatography. The derivatives represent materials of high thermal stability with initial thermal destruction temperatures from 390°C to 400 °C. The glass transition temperatures of the amorphous materials were 182 °C, 151 °C and 159 °C respectively. Hole-transporting properties of the polymeric materials were tested in the structures of organic light emitting diodes with Alq3 as the green emitter and electron transporting material. The device containing hole-transporting layers of polymer with 2-(4-biphenyl)-7-(4-vinylphenyl)-9,9-diethylfluorene moieties exhibited the best overall performance with turn on voltage of 3.6 V, a maximum photometric efficiency of 3.1 cd/A and maximum brightness of about 5300 cd/m2.

Identification of a Surrogate Marker for Infection in the African Green Monkey Model of Inhalation Anthrax

DTIC Science & Technology

2008-12-01

as well as condition and clarity of eyes and nose; clinical signs included breathing rate and pattern; natural behavior included peer interaction ...human cases, fatigue and/or mal- aise was a presenting symptom in only 64% of cases (26). While decreased activity and interaction were noted in some...experimental infection with Leishmania leishmania donovani and Leishmania leishmania infantum. Lab. Anim. Sci. 43:37–47. 5. Brachman, P. S. 1980

Enabling technologies and green processes in cyclodextrin chemistry.

PubMed

Cravotto, Giancarlo; Caporaso, Marina; Jicsinszky, Laszlo; Martina, Katia

2016-01-01

The design of efficient synthetic green strategies for the selective modification of cyclodextrins (CDs) is still a challenging task. Outstanding results have been achieved in recent years by means of so-called enabling technologies, such as microwaves, ultrasound and ball mills, that have become irreplaceable tools in the synthesis of CD derivatives. Several examples of sonochemical selective modification of native α-, β- and γ-CDs have been reported including heterogeneous phase Pd- and Cu-catalysed hydrogenations and couplings. Microwave irradiation has emerged as the technique of choice for the production of highly substituted CD derivatives, CD grafted materials and polymers. Mechanochemical methods have successfully furnished greener, solvent-free syntheses and efficient complexation, while flow microreactors may well improve the repeatability and optimization of critical synthetic protocols.

Green-light-emitting electroluminescent device based on a new cadmium complex

NASA Astrophysics Data System (ADS)

Kumar, Rahul; Srivastava, Ritu; Kumar, Akshay; Kamalasanan, M. N.; Singh, K.

2010-06-01

A new cadmium complex is synthesized to investigate its stability and applicability for a luminescent device. The as-prepared Cd(Bpy)q sample is characterized by Fourier-transformed infra-red spectroscopy (FTIR), thermal gravimetric analyzer (TGA) and photoluminescence (PL). The prepared sample shows excellent thermal stability up to 380 °C. A maximum is observed at 240 nm in absorption spectra which is attributed to the π-π* transition. An organic-light-emitting diode (OLED) has been fabricated using this material. The fundamental structures of the device exhibit ITO/α-NPD/Cd(Bpy)q/BCP/Alq3/LiF/Al. The electroluminescence (EL) device emits bright green light with maximum luminescence 1683 cd/m2 at 20 V.

Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

PubMed

Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

2013-12-01

Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

Development of MGD007, a gpA33 x CD3 bispecific DART® protein for T-cell immunotherapy of metastatic colorectal cancer.

PubMed

Moore, Paul A; Shah, Kalpana; Yang, Yinhua; Alderson, Ralph; Roberts, Penny; Long, Vatana; Liu, Daorong; Li, Jonathan C; Burke, Steve; Ciccarone, Valentina; Li, Hua; Fieger, Claudia B; Hooley, Jeff; Easton, Ann; Licea, Monica; Gorlatov, Sergey; King, Kathleen L; Young, Peter; Adami, Arash; Loo, Deryk; Chichili, Gurunadh R; Liu, Liqin; Smith, Douglas H; Brown, Jennifer G; Chen, Francine Z; Koenig, Scott; Mather, Jennie; Bonvini, Ezio; Johnson, Syd

2018-06-04

We have developed MGD007 (anti-glycoprotein A33 x anti-CD3), a DART® protein designed to redirect T-cells to target gpA33 expressing colon cancer. The gpA33 target was selected based on an antibody-based screen to identify cancer antigens universally expressed in both primary and metastatic CRC specimens, including putative cancer stem cell populations. MGD007 displays the anticipated bispecific binding properties and mediates potent lysis of gpA33-positive cancer cell lines, including models of colorectal cancer stem cells, through recruitment of T-cells. Xenograft studies showed tumor growth inhibition at doses as low as 4 µg/kg. Both CD8 and CD4 T cells mediated lysis of gpA33-expressing tumor cells, with activity accompanied by increases in granzyme and perforin. Notably, suppressive T-cell populations could also be leveraged to mediate lysis of gpA33 expressing tumor cells. Concomitant with CTL activity, both T-cell activation and expansion are observed in a gpA33-dependent manner. No cytokine activation was observed with human PBMC alone, consistent with the absence of gpA33 expression on peripheral blood cell populations. Following prolonged exposure to MGD007 and gpA33 positive tumor cells, T cells express PD 1 and LAG-3 and acquire a memory phenotype but retain ability to support potent cell killing. In cynomolgus monkeys, 4 weekly doses of 100 µg/kg were well tolerated, with prolonged PK consistent with that of an Fc-containing molecule. Taken together MGD007 displays potent activity against colorectal cancer cells consistent with a mechanism of action endowed in its design and support further investigation of MGD007 as a potential novel therapeutic treatment for colorectal cancer. Copyright ©2018, American Association for Cancer Research.

Sonochemical synthesis and DFT studies of nano novel Schiff base cadmium complexes: Green, efficient, recyclable catalysts and precursors of Cd NPs

NASA Astrophysics Data System (ADS)

Parsaee, Zohreh

2017-10-01

Novel asymmetric (N4) Schiff bases (Ln, n = 1-3) and their nanosized cadmium complexes derived of 4,4'-(pentylazanediyl) dibenzaldehyde and aminobenzaldehyde are synthesized by sonochemical method and characterized based on physicochemical analysis including 1H NMR, 13C NMR, SEM, TGA, Mass, FT-IR, UV-Vis spectroscopy, elemental analysis, magnetic moment and molar conductance measurements. According to the analytic results of the NMR, UV-Vis and magnetic moment studies, it is found that the geometrical structures of these complexes [CdII2LnCl4], (L = C45H40N5X, X = CH3, Cl, OH) are square planer. The synthesized complexes were so effective as nanocatalyst on the oxidation of primary and secondary alcohols. The oxidation reactions were carried out in ethyl-methyl-imidazolium ionic liquid in presence of NaOCl. In addition Cd NPs were synthesized through the thermal decomposition of mentioned complexes and characterized by using FT-IR, SEM, TEM, EDX and XRD methods, which indicated close accordance to the standard pattern of CdO nanoparticles and an acceptable size at the nanorange (22-27 nm). Furthermore geometrical optimization of the Cd2LnCl4 calculated using DFT/B3LYP with LanL2DZ/6-311+G (d,p) level. The electronic parameter including HOMO-LUMO orbitals, bond gap, chemical hardness-softness, electronegativity, electrophilicity, NMR chemical shifts and IR frequencies were calculated. The calculated NMR shifts and vibrational frequencies showed excellent agreement with experimental data.

Synergetic Influences of Mixed-Host Emitting Layer Structures and Hole Injection Layers on Efficiency and Lifetime of Simplified Phosphorescent Organic Light-Emitting Diodes.

PubMed

Han, Tae-Hee; Kim, Young-Hoon; Kim, Myung Hwan; Song, Wonjun; Lee, Tae-Woo

2016-03-09

We used various nondestructive analyses to investigate various host material systems in the emitting layer (EML) of simple-structured, green phosphorescent organic light-emitting diodes (OLEDs) to clarify how the host systems affect its luminous efficiency (LE) and operational stability. An OLED that has a unipolar single-host EML with conventional poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PSS) showed high operating voltage, low LE (∼26.6 cd/A, 13.7 lm/W), and short lifetime (∼4.4 h @ 1000 cd/m(2)). However, the combined use of a gradient mixed-host EML and a molecularly controlled HIL that has increased surface work function (WF) remarkably decreased operating voltage and improved LE (∼68.7 cd/A, 77.0 lm/W) and lifetime (∼70.7 h @ 1000 cd/m(2)). Accumulated charges at the injecting interfaces and formation of a narrow recombination zone close to the interfaces are the major factors that accelerate degradation of charge injection/transport and electroluminescent properties of OLEDs, so achievement of simple-structured OLEDs with high efficiency and long lifetime requires facilitating charge injection and balanced transport into the EML and distributing charge carriers and excitons in EML.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies

PubMed Central

Pietsch, E C; Dong, J; Cardoso, R; Zhang, X; Chin, D; Hawkins, R; Dinh, T; Zhou, M; Strake, B; Feng, P-H; Rocca, M; Santos, C Dos; Shan, X; Danet-Desnoyers, G; Shi, F; Kaiser, E; Millar, H J; Fenton, S; Swanson, R; Nemeth, J A; Attar, R M

2017-01-01

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices. PMID:28234345

Impact of different feedstocks derived biochar amendment with cadmium low uptake affinity cultivar of pak choi (Brassica rapa ssb. chinensis L.) on phytoavoidation of Cd to reduce potential dietary toxicity.

PubMed

Yasmin Khan, Kiran; Ali, Barkat; Cui, Xiaoqiang; Feng, Ying; Yang, Xiaoe; Joseph Stoffella, Peter

2017-07-01

Biochar has become eco-friendly amendment used for phytoavoidation with low cadmium (Cd) accumulating cultivars of crops to ensure food safety in Cd contaminated soils. In this study, biochar with different waste feedstock material were evaluated for their effectiveness on essential trace metals mobility, Cd bioavailability and its accumulation in two contrasting Cd accumulating cultivars of pak choi (Brassica rapa ssp. chinensis L.) grown in Cd contaminated Mollisol soil. A greenhouse experiment was conducted with plants grown in Cd contaminated soil that had been amended with biochar derived from barley straw, tomato green waste, chicken manure, duck manure and swine manure at application rate of 0%, 2.5% and 5.0% (w/w). The results showed that soil pH was significantly increased by all treatments. Biochar increased plant dry biomass, micronutrients bioavailability with significant differences in the Cd sorption capacity, with the effectiveness higher with increasing biochar application rate. However, tomato green waste (TGW) and chicken manure (CM) derived biochar were more effective than the other biochar in reducing Cd mobilization in soil by 35-54% and 26-43% and reduced its accumulation in shoots of pak choi cultivars by 34-76% and 33-72% in low Cd accumulator cultivar and 64-85% and 55-80% in high Cd accumulator cultivar than the control. Overall, results indicate that TGW and CM biochar can efficiently immobilize Cd, thereby reducing bioavailability in Cd contaminated Mollisol soil to ensure food safety. Copyright © 2017 Elsevier Inc. All rights reserved.

Simple and green synthesis of protein-conjugated CdS nanoparticles and spectroscopic study on the interaction between CdS and zein

NASA Astrophysics Data System (ADS)

Qin, Dezhi; Zhang, Li; Du, Xian; Wang, Yabo; Zhang, Qiuxia

2016-09-01

The present study demonstrates the role of zein molecules in synthesizing CdS nanoassemblies through protein-directed, green synthetic approach. Zein molecules can as capping ligand and stabilizing agent to regulate the nucleation and growth of CdS nanocrystals, and the obtained products are organic-inorganic nanocomposites. The analysis of surface charge and conductivity indicates that strong electrostatic force restricts mobility of ions, which creates a local supersaturation surrounding the binding sites of zein and reduces the activated energy of nucleation. The interaction between Cd2+/CdS and zein molecules was systematically investigated through spectroscopy techniques. Fourier transform infrared (FT-IR) spectra were used to envisage the binding of the functional groups of zein with the surface of CdS nanoparticles. Ultraviolet visible (UV-Vis) and photoluminescence (PL) spectra results show that Cd2+/CdS might interact with the aromatic amino acids of protein molecules and change its chemical microenvironment. The quantum-confined effect of nanocrystals is confirmed by optical absorption spectrum due to the small size (3-5 nm) of CdS particles. The data of circular dichroism (CD) spectra indicate that the formation of CdS nanocrystals could lead to the conformational change of zein molecules. Moreover, the possible mechanism of CdS nanocrystals growth in zein solution was also discussed. The weak interactions such as Van der Waals, hydrophobic forces and hydrogen bonds in zein molecules should play a crucial factor in the self-assembly of small nanoparticles.

Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate.

PubMed

Fujiki, Hirota; Sueoka, Eisaburo; Rawangkan, Anchalee; Suganuma, Masami

2017-12-01

Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and that EGCG and green tea extract prevent cancer development in a wide range of target organs in rodents. Therefore, we focused our attention on human cancer stem cells (CSCs) as targets of cancer prevention and treatment with EGCG. The numerous reports concerning anticancer activity of EGCG against human CSCs enriched from cancer cell lines were gathered from a search of PubMed, and we hope our review of the literatures will provide a broad selection for the effects of EGCG on various human CSCs. Based on our theoretical study, we discuss the findings as follows: (1) Compared with the parental cells, human CSCs express increased levels of the stemness markers Nanog, Oct4, Sox2, CD44, CD133, as well as the EMT markers, Twist, Snail, vimentin, and also aldehyde dehydrogenase. They showed decreased levels of E-cadherin and cyclin D1. (2) EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs. (3) EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs. (4) The inhibition of EGCG of the stemness of CSCs was weaker compared with parental cells. (5) The weak inhibitory activity of EGCG increased synergistically in combination with anticancer drugs. Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.

Green digital signage using nanoparticle embedded narrow-gap field sequential TN-LCDs

NASA Astrophysics Data System (ADS)

Kobayashi, Shunsuke; Shiraishi, Yukihide; Sawai, Hiroya; Toshima, Naoki; Okita, Masaya; Takeuchi, Kiyofumi; Takatsu, Haruyoshi

2012-03-01

We have fabricated field sequential color (FSC)-LCDs using cells and modules of narrow-gap TN-LCDs with and without doping the nanoparticles of PCyD-ZrO2 and AF-SiO2. It is shown that the FSC-LCD exhibits a high optical efficiency of OE=4.5 that is defined as OE=[Luminance]/[W/m2]=(cd/W). This figure may provide us a good reference or to clear the Energy Star Program Version 5-3 that issues a guideline: LCD with 50 inch on the diagonal consumes the energy of 108W. Through this research it is claimed that our FSC=LCD may be a novel green digital signage.

Isolation, molecular cloning and in vitro expression of rhesus monkey (Macaca mulatta) prominin-1.s1 complementary DNA encoding a potential hematopoietic stem cell antigen.

PubMed

Husain, S M; Shou, Y; Sorrentino, B P; Handgretinger, R

2006-10-01

Human prominin-1 (CD133 or AC133) is an important cell surface marker used to isolate primitive hematopoietic stem cells. The commercially available antibody to human prominin-1 does not recognize rhesus prominin-1. Therefore, we isolated, cloned and characterized the complementary DNA (cDNA) of rhesus prominin-1 gene and determined its coding potential. Following the nomenclature of prominin family of genes, we named this cDNA as rhesus prominin-1.s1. The amino acid sequence data of the putative rhesus prominin-1.s1 could be used in designing antigenic peptides to raise antibodies for use in isolation of pure populations of rhesus prominin-1(+) hematopoietic cells. To the best of our knowledge, there has been no previously published report about the isolation of a prominin-1 cDNA from rhesus monkey (Macaca mulatta).

The differentiation of hepatocyte-like cells from monkey embryonic stem cells.

PubMed

Ma, Xiaocui; Duan, Yuyou; Jung, Christine J; Wu, Jian; VandeVoort, Catherine A; Zern, Mark A

2008-12-01

Embryonic stem cells (ESC) hold great potential for the treatment of liver diseases. Here, we report the differentiation of rhesus macaque ESC along a hepatocyte lineage. The undifferentiated monkey ESC line, ORMES-6, was cultured in an optimal culture condition in an effort to differentiate them into hepatocyte-like cells in vitro. The functional efficacy of the differentiated hepatic cells was evaluated using RT-PCR for the expression of hepatocyte specific genes, and Western blot analysis and immunocytochemistry for hepatic proteins such as alpha-fetoprotein (AFP), albumin and alpha1-antitrypsin (alpha1-AT). Functional assays were performed using the periodic acid schiff (PAS) reaction and ELISA. The final yield of ESC-derived hepatocyte-like cells was measured by flow cytometry for cells that were transduced with a liver-specific lentivirus vector containing the alpha1-AT promoter driving the expression of green fluorescence protein (GFP). The treatment of monkey ESC with an optimal culture condition yielded hepatocyte-like cells that expressed albumin, alpha1-AT, AFP, hepatocyte nuclear factor 3beta, glucose-6-phophatase, and cytochrome P450 genes and proteins as determined by RT-PCR and Western blot analysis. Immunofluorescent staining showed the cells positive for albumin, AFP, and alpha1-AT. PAS staining demonstrated that the differentiated cells showed hepatocyte functional activity. Albumin could be detected in the medium after 20 days of differentiation. Flow cytometry data showed that 6.5 +/- 1.0% of the total differentiated cells were positive for GFP. These results suggest that by using a specific, empirically determined, culture condition, we were able to direct monkey ESC toward a hepatocyte lineage.

Extremely Low Roll-Off and High Efficiency Achieved by Strategic Exciton Management in Organic Light-Emitting Diodes with Simple Ultrathin Emitting Layer Structure.

PubMed

Zhang, Tianmu; Shi, Changsheng; Zhao, Chenyang; Wu, Zhongbin; Chen, Jiangshan; Xie, Zhiyuan; Ma, Dongge

2018-03-07

Phosphorescent organic light-emitting diodes (OLEDs) possess the property of high efficiency but have serious efficiency roll-off at high luminance. Herein, we manufactured high-efficiency phosphorescent OLEDs with extremely low roll-off by effectively locating the ultrathin emitting layer (UEML) away from the high-concentration exciton formation region. The strategic exciton management in this simple UEML architecture greatly suppressed the exciton annihilation due to the expansion of the exciton diffusion region; thus, this efficiency roll-off at high luminance was significantly improved. The resulting green phosphorescent OLEDs exhibited the maximum external quantum efficiency of 25.5%, current efficiency of 98.0 cd A -1 , and power efficiency of 85.4 lm W -1 and still had 25.1%, 94.9 cd A -1 , and 55.5 lm W -1 at 5000 cd m -2 luminance, and retained 24.3%, 92.7 cd A -1 , and 49.3 lm W -1 at 10 000 cd m -2 luminance, respectively. Compared with the usual structures, the improvement demonstrated in this work displays potential value in applications.

CdS quantum dots confined in mesoporous TiO2 with exceptional photocatalytic performance for degradation of organic polutants.

PubMed

Zhou, Panpan; Xie, Yu; Fang, Jing; Ling, Yun; Yu, Changling; Liu, Xiaoming; Dai, Yuhua; Qin, Yuancheng; Zhou, Dan

2017-07-01

In this paper, the mesoporous TiO 2 with different concentration of CdS quantum dots (i.e., x% CdS/TiO 2 ) was successfully fabricated by the sol-gel method. The composition, structure and morphology of the nanocomposites were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), UV-vis diffuse reflectance spectroscopy (UV-Vis/DRS) and nitrogen physical adsorption test and so on. The proportion of CdS and TiO 2 is very important for the photocatalytic performance. As a result, the photocatalytic degradation performance from the most to the least is in the order of 2% CdS/TiO 2 , 4% CdS/TiO 2 , 8% CdS/TiO 2 , pure TiO 2 and 1% CdS/TiO 2 . The photocatalytic (PC) activity of the 2% CdSTiO 2 is characterized by photocatalytic degradation of methyl orange, which can be completely degraded within 45 min better than 60 min TiO 2 takes. It is also much better than CdS. Moreover, other four organic pollutants, such as methylthionine chloride, bisphenol A, rhodamine B, malachite green can also be degraded quickly on the condition of 2% CdS/TiO 2 . What's more, the chemical stability and cycling capability of 2% CdS/TiO 2 are reflected by five cyclic degradation of methyl orange. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities.

PubMed

France, C P; Medzihradsky, F; Woods, J H

1994-01-01

Bremazocine, [5R-(5,7,8 beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro [4,5]dec-8-yl]-4-benzofuranacetamide (Cl-977), (+-)-trans-3,4-dichloro-N- methyl-(2-(pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetrahydronapth++ +-1-yl benzeneacetamide methanesulfonate (DUP 747), ethylketocyclazocine (EKC), nalorphine, (+/-)-trans-N-methyl-N-[2-(1- pyrrolidnyl)-cyclohexyl]benzo[b]thiophene-4-acetamide (PD117302), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide (U-50,488), (5,7,8 beta)-N-methyl-N[2-(1- pyrrolidinyl), 1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U-69,593) and spiradoline were compared in rhesus monkeys for their discriminative stimulus, analgesic and respiratory effects. Selected compounds also were studied for their binding affinities at mu [[3H](D-Ala2-Me-Phe4,Glyol5)enkephalin], kappa ([3H]U-69,593) and delta [[3H](D-Pen2-D-Pen5) enkephalin], opioid receptors in monkey brain membranes. All compounds substituted completely (> or = 90%) for EKC in monkeys discriminating between EKC and saline, with the exception that DUP 747 produced a maximum of 74% EKC responding. None of the compounds reversed naltrexone responding in morphine-abstinent monkeys; all of the compounds substituted for naltrexone in morphine-treated monkeys discriminating between naltrexone and saline, with the exception that spiradoline produced a maximum of 68% naltrexone responding. Eight compounds produced maximum analgesic effects in a tail withdrawal procedure and quadazocine antagonized these effects; nalorphine did not have analgesic effects, but it antagonized analgesic effects of several other compounds. U-50,488 did not decrease respiratory function, whereas U-69,593 decreased frequency of respiration and volume of respiration to less than 40% of control values; Cl-977, DUP 747, PD117302 and spiradoline had limited effects on respiratory function. Larger doses of each compound increased both respiration and motor activity.

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, R.P.; Ritter, L.

1989-01-01

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of themore » forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical.« less

Electroluminescence of organic light-emitting diodes consisting of an undoped (pbi)2Ir(acac) phosphorescent layer

NASA Astrophysics Data System (ADS)

Lei, Xia; Yu, Junsheng; Zhao, Juan; Jiang, Yadong

2011-11-01

The electroluminescence (EL) characteristics of phosphorescent organic light-emitting diodes (OLEDs) with an undoped bis(1,2-dipheny1-1H-benzoimidazole) iridium (acetylacetonate) [(pbi)2Ir(acac)] emissive layer (EML) of various film thicknesses were studied. The results showed that the intensity of green light emission decreased rapidly with the increasing thickness of (pbi)2Ir(acac), which was relevant to the triplet excimer emission. It suggested that the concentration quenching of monomer emission in the undoped (pbi)2Ir(acac) film was mainly due to the formation of triplet excimer and partly due to the triplet-triplet annihilation (TTA) and triplet-polaron annihilation (TPA). A green OLED with a maximum luminance of 26,531 cd/m2, a current efficiency of 36.2 cd/A, and a power efficiency of 32.4 lm/W was obtained, when the triplet excimer emission was eliminated. Moreover, the white OLED with low efficiency roll-off was realized due to the broadened recombination zone and reduced quenching effects in the EML when no electron blocking layer was employed.

Metabolism and disposition of ABT-894, a novel α4β2 neuronal acetylcholine receptor agonist, in mice and monkeys.

PubMed

Liu, Hong; Fu, Wentao; Wetter, Jill; Xu, Hongyu; Guan, Zhiwen; Stuart, Patricia

2014-06-01

1.  Metabolism and disposition of ABT-894 was investigated in hepatocytes, in mice and monkeys receiving [(14)C]ABT-894. 2.  In hepatocytes, turnover rate of ABT-894 was slow in all species with more than 90% of parent remaining. M3 (carbamoyl glucuronide) and M6 (mono-oxidation) were detected across species. 3.  ABT-894 showed species-specific disposition profiles. ABT-894 was primarily eliminated by renal secretion in mice. Whereas, monkey mainly cleared ABT-894 metabolically. 4.  ABT-894 underwent two primary routes of metabolism in monkeys: N-carbamoyl glucuronidation to form M3 and oxidation product M1. M3 was the major metabolite in monkey excreta. M3 was observed in mice urine. Circulating levels of M3 in terms of M3/ABT-894 ratios were essentially absent in mice, but were high in monkeys. 5.  Understanding the species difference in the clearance mechanism is the key to the accurate projection of the human clearance and preclinical safety assessment. Lack of species difference in the metabolism of ABT-894 in hepatocytes certainly creates a challenge in predicting its metabolism and pharmacokinetics in human. Based on available metabolism and pharmacokinetic data of ABT-894 in human, monkey is the preferred species in predicting human clearance since it presents a similar clearance mechanism from that observed in human.

Ultrapure Green Light-Emitting Diodes Using Two-Dimensional Formamidinium Perovskites: Achieving Recommendation 2020 Color Coordinates.

PubMed

Kumar, Sudhir; Jagielski, Jakub; Kallikounis, Nikolaos; Kim, Young-Hoon; Wolf, Christoph; Jenny, Florian; Tian, Tian; Hofer, Corinne J; Chiu, Yu-Cheng; Stark, Wendelin J; Lee, Tae-Woo; Shih, Chih-Jen

2017-09-13

Pure green light-emitting diodes (LEDs) are essential for realizing an ultrawide color gamut in next-generation displays, as is defined by the recommendation (Rec.) 2020 standard. However, because the human eye is more sensitive to the green spectral region, it is not yet possible to achieve an ultrapure green electroluminescence (EL) with a sufficiently narrow bandwidth that covers >95% of the Rec. 2020 standard in the CIE 1931 color space. Here, we demonstrate efficient, ultrapure green EL based on the colloidal two-dimensional (2D) formamidinium lead bromide (FAPbBr 3 ) hybrid perovskites. Through the dielectric quantum well (DQW) engineering, the quantum-confined 2D FAPbBr 3 perovskites exhibit a high exciton binding energy of 162 meV, resulting in a high photoluminescence quantum yield (PLQY) of ∼92% in the spin-coated films. Our optimized LED devices show a maximum current efficiency (η CE ) of 13.02 cd A -1 and the CIE 1931 color coordinates of (0.168, 0.773). The color gamut covers 97% and 99% of the Rec. 2020 standard in the CIE 1931 and the CIE 1976 color space, respectively, representing the "greenest" LEDs ever reported. Moreover, the device shows only a ∼10% roll-off in η CE (11.3 cd A -1 ) at 1000 cd m -2 . We further demonstrate large-area (3 cm 2 ) and ultraflexible (bending radius of 2 mm) LEDs based on 2D perovskites.

The potential protective effect of green, black, red and white tea infusions against adverse effect of cadmium and lead during chronic exposure - A rat model study.

PubMed

Winiarska-Mieczan, Anna

2015-11-01

The protective effect of green (GT), black (BT), red (RT) and white (WT) tea infusions on the lungs, brains, hearts, livers and kidneys of adult Wistar rats exposed to Cd (7 mg/kg) and Pb (50 m/kg) was studied. The degree of reduction in the absorption of Cd and Pb in the organs compared to control group and the activity of SOD, CAT and GPx as well as GSH level was evaluated. It was determined that tea significant reduced the accumulation of Cd in the tissues. A significant reduction in the accumulation of Pb was recorded in the brain (WT), liver (GT, WT) and kidneys (BT, GT, RT, WT). A significant increase was observed in the activity of SOD, CAT and GPx in the organs of all rats from tea groups. It was found that the results obtained in rats receiving black, red and white tea were overall not worse than those recorded for rats receiving green tea. The obtained results suggest that drinking tea could be an effective method of reducing the adverse effect of environmental Cd and Pb pollution on the human body. Copyright © 2015 Elsevier Inc. All rights reserved.

Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis

PubMed Central

Calascibetta, Francesca; Micci, Luca; Carnathan, Diane; Lawson, Benton; Vanderford, Thomas H.; Bosinger, Steven E.; Easley, Kirk; Chahroudi, Ann; Mackel, Joseph; Keele, Brandon F.; Long, Samuel; Lifson, Jeffrey; Paiardini, Mirko

2016-01-01

ABSTRACT Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4+ central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9-, 1.1-, 1.5-, and 3.7-fold for CD4+ transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4+ TCM cells, (ii) increased levels of CD4+ T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR+ CD8+ T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4+ TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV-infected sooty mangabeys, a natural host for the infection, with a potent antiretroviral therapy (ART) regimen for periods ranging from 2 to 12 months and monitored in detail how suppression of virus replication affected the main virological and immunological features of this nonpathogenic infection. The observed findings provide novel information on both the pathogenesis of residual immunological disease under ART during pathogenic infection and the mechanisms involved in virus persistence during primate lentiviral infections. PMID:27279614

Elevated numbers of CD163+ macrophages in hearts of simian immunodeficiency virus-infected monkeys correlate with cardiac pathology and fibrosis.

PubMed

Walker, Joshua A; Sulciner, Megan L; Nowicki, Katherine D; Miller, Andrew D; Burdo, Tricia H; Williams, Kenneth C

2014-07-01

The role of macrophage activation, traffic, and accumulation on cardiac pathology was examined in 23 animals. Seventeen animals were simian immunodeficiency virus (SIV) infected, 12 were CD8 lymphocyte depleted, and the remaining six were uninfected controls (two CD8 lymphocyte depleted, four nondepleted). None of the uninfected controls had cardiac pathology. One of five (20%) SIV-infected, non-CD8 lymphocyte-depleted animals had minor cardiac pathology with increased numbers of macrophages in ventricular tissue compared to controls. Seven of the 12 (58%) SIV-infected, CD8 lymphocyte-depleted animals had cardiac pathology in ventricular tissues, including macrophage infiltration and myocardial degeneration. The extent of fibrosis (measured as the percentage of collagen per tissue area) was increased 41% in SIV-infected, CD8 lymphocyte-depleted animals with cardiac pathology compared to animals without pathological abnormalities. The number of CD163+ macrophages increased significantly in SIV-infected, CD8 lymphocyte-depleted animals with cardiac pathology compared to ones without pathology (1.66-fold) and controls (5.42-fold). The percent of collagen (percentage of collagen per total tissue area) positively correlated with macrophage numbers in ventricular tissue in SIV-infected animals. There was an increase of BrdU+ monocytes in the heart during late SIV infection, regardless of pathology. These data implicate monocyte/macrophage activation and accumulation in the development of cardiac pathology with SIV infection.

Coexistence of strongly and weakly confined energy levels in (Cd,Zn)Se quantum dots: Tailoring the near-band-edge and defect-levels for white light emission

NASA Astrophysics Data System (ADS)

Das, Tapan Kumar; Ilaiyaraja, P.; Sudakar, C.

2017-05-01

We demonstrate white light emission (WLE) from (Cd,Zn)Se system, which is a composite of Zn alloyed CdSe quantum dot and ZnSe-amorphous (ZnSe-a) phase. Detailed structural and photoluminescence emission studies on pure CdSe and (Cd,Zn)Se show cubic zinc blende structure in the size range of 2.5 to 5 nm. (Cd,Zn)Se quantum dots (QDs) also have a significant fraction of ZnSe-a phase. The near-band-edge green-emission in crystalline CdSe and (Cd,Zn)Se is tunable between 500 to 600 nm. The (Cd,Zn)Se system also exhibits a broad, deep defect level (DL) red-emission in the range 600 to 750 nm and a sharp ZnSe near-band-edge blue-emission (ZS-NBE) between 445 to 465 nm. While DL and CdSe near-band-edge (CS-NBE) emissions significantly shift with the size of QD due to strong confinement effect, the ZS-NBE show minimal change in peak position indicating a weak confinement effect. The intensities of ZS-NBE and DL emissions also exhibit a strong dependence on the QD size. A gamut of emission colors is obtained by combining the CS-NBE with the ZS-NBE emission and broad DL emission in (Cd,Zn)Se system. Interestingly, we find the convergence of Commission Internationale de l'Eclairage (CIE) coordinates towards the white light with increasing Zn concentration in CdSe. We demonstrate by combining these three emissions in a proper weight ratio WLE can be achieved. Cd1-yZnySe (y = 0. 5; QD size ˜4.9 nm) alloy with a maximum quantum yield of 57% exhibits CIE coordinates of (0.39, 0.4), color rendering index (CRI) of 82, correlated color temperature (CCT) of 3922 K, and Duv of 0.0078 which is very promising for white light applications.

A Biomechanical Analysis Of Craniofacial Form And Function

NASA Astrophysics Data System (ADS)

Oyen, Ordean J.

1989-04-01

In vivo measures of bite force and bone strain obtained in growing African green monkeys (Cercopeithecus aethiops) are being used to study skull biology and geometry. Strain values and distributional patterns seen in association with forceful jaw elevation are inconsistent with conventional explanations linking upper facial morphology with masticatory function and/or using beam models of craniofacial architecture. These results mandate careful use of notions about skeletal geometry based on static analyses that have not been experimentally verified using in vivo procedures.

Genetically engineered Pseudomonas putida X3 strain and its potential ability to bioremediate soil microcosms contaminated with methyl parathion and cadmium.

PubMed

Zhang, Rong; Xu, Xingjian; Chen, Wenli; Huang, Qiaoyun

2016-02-01

A multifunctional Pseudomonas putida X3 strain was successfully engineered by introducing methyl parathion (MP)-degrading gene and enhanced green fluorescent protein (EGFP) gene in P. putida X4 (CCTCC: 209319). In liquid cultures, the engineered X3 strain utilized MP as sole carbon source for growth and degraded 100 mg L(-1) of MP within 24 h; however, this strain did not further metabolize p-nitrophenol (PNP), an intermediate metabolite of MP. No discrepancy in minimum inhibitory concentrations (MICs) to cadmium (Cd), copper (Cu), zinc (Zn), and cobalt (Co) was observed between the engineered X3 strain and its host strain. The inoculated X3 strain accelerated MP degradation in different polluted soil microcosms with 100 mg MP kg(-1) dry soil and/or 5 mg Cd kg(-1) dry soil; MP was completely eliminated within 40 h. However, the presence of Cd in the early stage of remediation slightly delayed MP degradation. The application of X3 strain in Cd-contaminated soil strongly affected the distribution of Cd fractions and immobilized Cd by reducing bioavailable Cd concentrations with lower soluble/exchangeable Cd and organic-bound Cd. The inoculated X3 strain also colonized and proliferated in various contaminated microcosms. Our results suggested that the engineered X3 strain is a potential bioremediation agent showing competitive advantage in complex contaminated environments.

Infection and persistence of rhesus monkey rhadinovirus in immortalized B-cell lines.

PubMed

Bilello, John P; Lang, Sabine M; Wang, Fred; Aster, Jon C; Desrosiers, Ronald C

2006-04-01

Similar to its close relative human herpesvirus 8, rhesus monkey rhadinovirus (RRV) persists predominantly in B cells of its natural host. Rhesus monkey B-cell lines immortalized by the Epstein-Barr-related virus from rhesus monkeys (rhEBV) were used as targets for infection by RRV. These cultured B cells were susceptible to infection by RRV and continued to produce low titers of RRV for months of continuous culture. Infection by RRV did not detectably alter the growth rates of these B-cell lines when it was measured at standard or reduced serum concentrations. Depending on the cell line, 5 to 40% of the B cells stained positive for the RRV genome by fluorescence in situ hybridization (FISH). Most RRV-positive cells showed a fine punctate nuclear staining pattern consistent with latent infection, while a small minority of cells (0.2 to 1%) contained large, intensely staining nuclear foci consistent with productive, replicative infection. Greater than 90% of the cells were rhEBV genome positive in a pattern consistent with latent infection, and again only a small minority of cells showed a productive, replicative staining pattern. Dual, two-color FISH staining revealed coinfection of numerous cells with both RRV and rhEBV, but productive replication of RRV and rhEBV was always observed in separate cells, never in the same cell. Thus, productive replication of RRV is unlinked to that of rhEBV; factors that influence activation to productive replication act separately on RRV and rhEBV, even within the same cell. The percentage of B cells expressing green fluorescent protein (GFP) early after infection with a recombinant RRV containing a GFP reporter gene was dose dependent and at a low multiplicity of infection increased progressively over time until 14 to 17 days after infection. These results establish a naturalistic cell culture system for the study of infection and persistence by RRV in rhesus monkey B cells.

Monkey Visual Short-Term Memory Directly Compared to Humans

PubMed Central

Elmore, L. Caitlin; Wright, Anthony A.

2015-01-01

Two adult rhesus monkeys were trained to detect which item in an array of memory items had changed using the same stimuli, viewing times, and delays as used with humans. Although the monkeys were extensively trained, they were less accurate than humans with the same array sizes (2, 4, & 6 items), with both stimulus types (colored squares, clip art), and showed calculated memory capacities of about one item (or less). Nevertheless, the memory results from both monkeys and humans for both stimulus types were well characterized by the inverse power-law of display size. This characterization provides a simple and straightforward summary of a fundamental process of visual short-term memory (how VSTM declines with memory load) that emphasizes species similarities based upon similar functional relationships. By more closely matching of monkey testing parameters to those of humans, the similar functional relationships strengthen the evidence suggesting similar processes underlying monkey and human VSTM. PMID:25706544

Can Monkeys (Macaca mulatta) Represent Invisible Displacement?

NASA Technical Reports Server (NTRS)

Filion, Christine M.; Washburn, David A.; Gulledge, Jonathan P.

1996-01-01

Four experiments were conducted to assess whether or not rhesus macaques (Macaca mulatta) could represent the unperceived movements of a stimulus. Subjects were tested on 2 computerized tasks, HOLE (monkeys) and LASER (humans and monkeys), in which subjects needed to chase or shoot at, respectively, a moving target that either remained visible or became invisible for a portion of its path of movement. Response patterns were analyzed and compared between target-visible and target-invisible conditions. Results of Experiments 1, 2, and 3 demonstrated that the monkeys are capable of extrapolating movement. That this extrapolation involved internal representation of the target's invisible movement was suggested but not confirmed. Experiment 4, however, demonstrated that the monkeys are capable of representing the invisible displacements of a stimulus.

Enabling technologies and green processes in cyclodextrin chemistry

PubMed Central

Caporaso, Marina; Jicsinszky, Laszlo; Martina, Katia

2016-01-01

Summary The design of efficient synthetic green strategies for the selective modification of cyclodextrins (CDs) is still a challenging task. Outstanding results have been achieved in recent years by means of so-called enabling technologies, such as microwaves, ultrasound and ball mills, that have become irreplaceable tools in the synthesis of CD derivatives. Several examples of sonochemical selective modification of native α-, β- and γ-CDs have been reported including heterogeneous phase Pd- and Cu-catalysed hydrogenations and couplings. Microwave irradiation has emerged as the technique of choice for the production of highly substituted CD derivatives, CD grafted materials and polymers. Mechanochemical methods have successfully furnished greener, solvent-free syntheses and efficient complexation, while flow microreactors may well improve the repeatability and optimization of critical synthetic protocols. PMID:26977187

Exposure to Sunlight Reduces the Risk of Myopia in Rhesus Monkeys

PubMed Central

Wang, Yong; Ding, Hui; Stell, William K.; Liu, Liangping; Li, Saiqun; Liu, Hongshan; Zhong, Xingwu

2015-01-01

Exposure to sunlight has recently been postulated as responsible for the effect that more time spent outdoors protects children from myopia, while early life exposure to natural light was reported to be possibly related to onset of myopia during childhood. In this study, we had two aims: to determine whether increasing natural light exposure has a protective effect on hyperopic defocus-induced myopia, and to observe whether early postnatal exposure to natural light causes increased risk of refractive error in adolescence. Eight rhesus monkeys (aged 20-30 days) were treated monocularly with hyperopic-defocus (-3.0D lens) and divided randomly into two groups: AL group (n=4), reared under Artificial (indoor) Lighting (08:00-20:00); and NL group (n=4), exposed to Natural (outdoor) Light for 3 hours per day (11:00-14:00), and to indoor lighting for the rest of the light phase. After being reared with lenses for ca. 190 days, all monkeys were returned to unrestricted vision until the age of 3 years. Another eight age-matched monkeys, reared with unrestricted vision under artificial lighting since birth, were employed as controls. The ocular refraction, corneal curvature and axial dimensions were measured before lens-wearing (at 23±3 days of age), monthly during the light phase, and at the age of puberty (at 1185+3 days of age). During the lens-wearing treatment, infant monkeys in the NL group were more hyperopic than those in the AL group (F=5.726, P=0.032). Furthermore, the two eyes of most NL monkeys remained isometropic, whereas 3 of 4 AL monkeys developed myopic anisometropia more than -2.0D. At adolescence, eyes of AL monkeys showed significant myopic anisometropia compared with eyes of NL monkeys (AL vs NL: -1.66±0.87D vs -0.22±0.44D; P=0.002) and controls (AL vs Control: -1.66±0.87D vs -0.05±0.85D; P<0.0001). All differences in refraction were associated with parallel changes in axial dimensions. Our results suggest that exposure to natural outdoor light might have an effect to reduced hyperopic defocus-induced myopia. Also, the data imply that early life exposure to sunlight may help to maintain normal development of emmetropization later in life, and thus lower the risk of myopic anisometropia in adolescent monkey. PMID:26030845

Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.

PubMed

Grégoire, Laurent; Samadi, Pershia; Graham, Julie; Bédard, Paul J; Bartoszyk, Gerd D; Di Paolo, Thérèse

2009-07-01

Dyskinesia is an important complication of treatment in Parkinson's disease (PD). Sarizotan, a 5-HT(1A) agonist with high affinity for D3 and D4 receptors was investigated on L-Dopa-induced dyskinesia (LID) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. Five MPTP female cynomolgus monkeys (Macaca fascicularis) with a moderate to severe parkinsonian syndrome and LID were used. Sarizotan 0.2, 1, and 2 mg/kg administered alone did not worsen parkinsonian symptoms; there were no effect on locomotor counts or on normal behavior of the monkeys. Sarizotan 0.2, 1, and 2 mg/kg administered 30 min before a fixed dose of L-Dopa (25-30 mg/kg s.c.) + benserazide (50 mg) did not affect the antiparkinsonian response to L-Dopa. However, mean dyskinetic scores were significantly reduced with sarizotan 1 and 2 mg/kg but not at 0.2 mg/kg. Higher doses of sarizotan (4 and 8 mg/kg, administered immediately before L-Dopa) reduced L-Dopa-induced locomotor response in all monkeys. A pharmacokinetic investigation in these monkeys showed a dose-dependent increase in mean plasma sarizotan concentrations with similar mean plasma concentrations for sarizotan 1 mg/kg alone or with L-Dopa, indicating a lack of sarizotan/L-Dopa interaction. The time course of plasma sarizotan concentrations was associated with time of maximal reduction of dyskinesias. When administered daily for two weeks in combination with L-Dopa in the same MPTP monkeys, sarizotan 1 mg/kg had a sustained antidyskinetic effect while maintaining the antiparkinsonian and locomotor effect of L-Dopa. This detailed sarizotan investigation in MPTP monkeys supports the antidyskinetic activity of this drug and for 5-HT(1A) agonists.

Evaluation of monkey intraocular pressure by rebound tonometer

PubMed Central

Yu, Wenhan; Cao, Guiqun; Qiu, Jinghua; Ma, Jia; Li, Ni; Yu, Man; Yan, Naihong; Chen, Lei; Pang, Iok-Hou

2009-01-01

Purpose To evaluate the usefulness of the TonoVet™ rebound tonometer in measuring intraocular pressure (IOP) of monkeys. Methods The accuracy of the TonoVet™ rebound tonometer was determined in cannulated eyes of anesthetized rhesus monkeys where IOP was controlled by adjusting the height of a connected perfusate reservoir. To assess the applicability of the equipment through in vivo studies, the diurnal fluctuation of IOP and effects of IOP-lowering compounds were evaluated in monkeys. Results IOP readings generated by the TonoVet™ tonometer correlated very well with the actual pressure in the cannulated monkey eye. The linear correlation had a slope of 0.922±0.014 (mean±SEM, n=4), a y-intercept of 3.04±0.61, and a correlation coefficient of r2=0.97. Using this method, diurnal IOP fluctuation of the rhesus monkey was demonstrated. The tonometer was also able to detect IOP changes induced by pharmacologically active compounds. A single topical ocular instillation (15 μg) of the rho kinase inhibitor, H1152, produced a 5–6 mmHg reduction (p<0.001) in IOP, lasting at least 4 h. In addition, topical administration of Travatan®, a prostaglandin agonist, induced a small transient IOP increase (1.1 mmHg versus vehicle control; p=0.26) at 2 h after treatment followed by a pressure reduction at 23 h (−2.4 mmHg; p<0.05). Multiple daily dosing with the drug produced a persistent IOP-lowering effect. Three consecutive days of Travatan treatment produced ocular hypotension of −2.0 to −2.2 mmHg (p<0.05) the following day. Conclusions The rebound tonometer was easy to use and accurately measured IOP in the rhesus monkey eye. PMID:19898690

Hypocretin/orexin antagonists decrease cocaine self-administration by female rhesus monkeys.

PubMed

Foltin, Richard W; Evans, Suzette M

2018-07-01

The hypocretin/orexin system is involved in regulating arousal, and much recent work demonstrates that decreasing hypocretin receptor-1 (HCRTr1) activity using antagonists decreases appetitive behavior, including stimulant drug self-administration and reinstatement. The present study determined the effects of hypocretin-1 and HCRTr1 antagonists on responding reinforced by intravenous (i.v.) cocaine self-administration (0.0125 - 0.05 mg/kg/infusion) in 5 female rhesus monkeys. Responding was examined using 3 schedules of reinforcement: 1) a Fixed interval 1 min, Fixed ratio 10 Chain schedule [FI 1-min (FR10:S)], 2) a Progressive Ratio (PR) schedule, and 3) a cocaine vs. candy. Choice schedule: the HCRTr1 antagonist SB-334867 (8-24 mg/kg, i.m.) decreased cocaine taking under the Chain schedule and PR schedule in all 5 monkeys and in 4 of the 5 monkeys under the Choice schedule. d- Amphetamine (0.06 - 0.25 mg/kg, i.m.), tested as a control manipulation, decreased cocaine taking in all 5 monkeys under the Chain schedule. The peptide hypocretin-1 (0.072 mg/kg, i.v.) increased cocaine taking in the monkeys with low rates of cocaine taking under the Chain (3/4) and Choice (4/5) schedules. Reinstatement of extinguished cocaine responding following response-independent delivery of a large dose of cocaine (0.3 mg/kg) was attenuated in 3 of the 5 monkeys by the HCRTr1 antagonist SB-334867. These data expand upon work accomplished in predominantly male rodents suggesting that the hypocretin system modulates the response to appetitive stimuli. A better understanding of this system offers promise as a novel approach in medication development for appetitive disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation

PubMed Central

Hisatomi, Toshio; Sonoda, Koh‐hei; Ishikawa, Fumihiko; Qiao, Hong; Nakamura, Takahiro; Fukata, Mitsuhiro; Nakazawa, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi‐Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

2007-01-01

Aims To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Methods Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild‐type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. Results GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. Conclusion We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU. PMID:17035278

Misleading and reliable markers to differentiate between primate testis-derived multipotent stromal cells and spermatogonia in culture

PubMed Central

Eildermann, K.; Gromoll, J.; Behr, R.

2012-01-01

BACKGROUND Several studies have reported the generation of spermatogonia-derived pluripotent stem cells from human testes. The initial aim of the present study was the derivation of equivalent stem cells from an established and experimentally accessible non-human primate model, the common marmoset monkey (Callithrix jacchus). However, an essential prerequisite in the absence of transgenic reporters in primates and man is the availability of validated endogenous markers for the identification of specific cell types in vitro. METHODS AND RESULTS We cultured marmoset testicular cells in a similar way to that described for human testis-derived pluripotent cells and set out to characterize these cultures under different conditions and in differentiation assays applying established marker panels. Importantly, the cells emerged as testicular multipotent stromal cells (TMSCs) instead of (pluripotent) germ cell-derived cells. TMSCs expressed many markers such as GFR-α, GPR125, THY-1 (CD90), ITGA6, SSEA4 and TRA-1-81, which were considered as spermatogonia specific and were previously used for the enrichment or characterization of spermatogonia. Proliferation of TMSCs was highly dependent on basic fibroblast growth factor, a growth factor routinely present in germ cell culture media. As reliable markers for the distinction between spermatogonia and TMSCs, we established VASA, in combination with the spermatogonia-expressed factors, MAGEA4, PLZF and SALL4. CONCLUSIONS Marmoset monkey TMSCs and spermatogonia exhibit an overlap of markers, which may cause erroneous interpretations of experiments with testis-derived stem cells in vitro. We provide a marker panel for the unequivocal identification of spermatogonia providing a better basis for future studies on primate, including human, testis-derived stem cells. PMID:22442249

Enterovirus 71 pathogenicity in monkeys and cotton rats.

PubMed

Koroleva, Galina A; Karmysheva, Valentina Ya; Lukashev, Alexander N

2014-05-01

Enterovirus 71 (EV71) is a neurovirulent non-polio enterovirus that can cause severe central nervous system (CNS) infection in infants. Vervet monkeys infected intracerebrally or intramuscularly with EV71 isolates from the Bulgarian outbreak of 1975 developed clinical manifestations and pathological signs of encephalomyelitis and spinal poliomyelitis that were similar to EV71 neuroinfection in children. In addition, vervet monkeys with encephalomyelitis had severe alterations in the choroid plexus. EV71 neuroinfection could also be reproduced in young (3- to 4-week old) cotton rats with clinical and pathological signs comparable with those observed in vervet monkeys.

Signaling Lymphocytic Activation Molecule Family Receptor Homologs in New World Monkey Cytomegaloviruses.

PubMed

Pérez-Carmona, Natàlia; Farré, Domènec; Martínez-Vicente, Pablo; Terhorst, Cox; Engel, Pablo; Angulo, Ana

2015-11-01

Throughout evolution, large DNA viruses have been usurping genes from their hosts to equip themselves with proteins that restrain host immune defenses. Signaling lymphocytic activation molecule (SLAM) family (SLAMF) receptors are involved in the regulation of both innate and adaptive immunity, which occurs upon engagement with their ligands via homotypic or heterotypic interactions. Here we report a total of seven SLAMF genes encoded by the genomes of two cytomegalovirus (CMV) species, squirrel monkey CMV (SMCMV) and owl monkey CMV (OMCMV), that infect New World monkeys. Our results indicate that host genes were captured by retrotranscription at different stages of the CMV-host coevolution. The most recent acquisition led to S1 in SMCMV. S1 is a SLAMF6 homolog with an amino acid sequence identity of 97% to SLAMF6 in its ligand-binding N-terminal Ig domain. We demonstrate that S1 is a cell surface glycoprotein capable of binding to host SLAMF6. Furthermore, the OMCMV genome encodes A33, an LY9 (SLAMF3) homolog, and A43, a CD48 (SLAMF2) homolog, two soluble glycoproteins which recognize their respective cellular counterreceptors and thus are likely to be viral SLAMF decoy receptors. In addition, distinct copies of further divergent CD48 homologs were found to be encoded by both CMV genomes. Remarkably, all these molecules display a number of unique features, including cytoplasmic tails lacking characteristic SLAMF signaling motifs. Taken together, our findings indicate a novel immune evasion mechanism in which incorporation of host SLAMF receptors that retain their ligand-binding properties enables viruses to interfere with SLAMF functions and to supply themselves with convenient structural molds for expanding their immunomodulatory repertoires. The way in which viruses shape their genomes under the continual selective pressure exerted by the host immune system is central for their survival. Here, we report that New World monkey cytomegaloviruses have broadly captured and duplicated immune cell receptors of the signaling lymphocyte activation molecule (SLAM) family during host-virus coevolution. Notably, we demonstrate that several of these viral SLAMs exhibit exceptional preservation of their N-terminal immunoglobulin domains, which results in maintenance of their ligand-binding capacities. At the same time, these molecules present distinctive structural properties which include soluble forms and the absence of typical SLAM signaling motifs in their cytoplasmic domains, likely reflecting the evolutionary adaptation undergone to efficiently interfere with host SLAM family activities. The observation that the genomes of other large DNA viruses might bear SLAM family homologs further underscores the importance of these molecules as a novel class of immune regulators and as convenient scaffolds for viral evolution. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

SOME EVIDENCE OF PSYCHIC BLINDNESS IN MONKEYS WITH FOCAL-HEAD IRRADIATION OF THE TEMPORAL LOBES

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, A.A.; Brown, W.L.

1963-12-01

This study was conducted to compare the effects of various extra-cage social stimuli on the free-cage behavior of normal monkeys and of monkeys with previous focal-head irradiation. Four control and four focal-head irradiated monkeys with nearly identical training histories were used, the latter being the survivors of a focal-head irradiation study conducted 41/2 yr earlier. They had received 3000 r x radiation to an area of the head containing the inferior parietal lobule and posterior aspect of the temporal lobe, and repeated 30 days later Each group was systematically observed under each of four socialstimulus conditions with the order ofmore » condition presentation counterbalanced within each group over a 4-day period. The four social-stimulus conditions included: absence of social stimulus, an adult male monkey, an adult female monkey at menses, and an adult female monkey at estimated time of ovulation. The socialstimulus conditions showed no effect on the nondirected activities of the normal monkeys, but produced a marked decrease in the nondirected activities of the focal-head irradiated monkeys, with the least number of such activities being manifest in the presence of the adult female monkey at ovulation. Under conditions of social stimulation the normal monkeys showed a marked decrease in total directed activities of the non-social-stimulus condition, while the focal-head irradiated monkeys showed a marked increase, the effect in each instance being greatest in the presence of the female at ovulation. The directed activities, toward the cage as an object, of the controls decreasrd and those of the experimental subjects increased. The controls were more than twice as responsive to the female at estimated time of ovulation as to the other two social stimuli, while the experimental monkeys were equally responsive to each of the three social stimuli. The data suggest the presence of psychic blindness in the monkeys previously exposed to focal-head irradiation of the temporal lobes. (BBB)« less

Cup tool use by squirrel monkeys.

PubMed

Buckmaster, Christine L; Hyde, Shellie A; Parker, Karen J; Lyons, David M

2015-12-01

Captive-born male and female squirrel monkeys spontaneously 'invented' a cup tool use technique to Contain (i.e., hold and control) food they reduced into fragments for consumption and to Contain water collected from a valve to drink. Food cup use was observed more frequently than water cup use. Observations indicate that 68% (n = 39/57) of monkeys in this population used a cup (a plastic slip cap) to Contain food, and a subset of these monkeys, 10% (n = 4/39), also used a cup to Contain water. Cup use was optional and did not replace, but supplemented, the hand/arm-to-mouth eating and direct valve drinking exhibited by all members of the population. Strategies monkeys used to bring food and cups together for food processing activity at preferred upper-level perching areas, in the arboreal-like environment in which they lived, provides evidence that monkeys may plan food processing activity with the cups. Specifically, prior to cup use monkeys obtained a cup first before food, or obtained food and a cup from the floor simultaneously, before transporting both items to upper-level perching areas. After food processing activity with cups monkeys rarely dropped the cups and more often placed the cups onto perching. Monkeys subsequently returned to use cups that they previously placed on perching after food processing activity. The latter behavior is consistent with the possibility that monkeys may keep cups at preferred perching sites for future food processing activity and merits experimental investigation. Reports of spontaneous tool use by squirrel monkeys are rare and this is the first report of population-level tool use. These findings offer insights into the cognitive abilities of squirrel monkeys and provide a new context for behavior studies with this genus and for comparative studies with other primates. © 2015 Wiley Periodicals, Inc.

[Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].

PubMed

Ma, Yan-bing; Xie, Tian-hong; Zhang, Guang-ming; Li, Chun-hong; Dai, Xie-Jie; Dai, Chang-bai; Sun, Mao-sheng; Lu, Jian; Bi, Sheng-li

2002-12-01

To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta). Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR. Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus. The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.

Effects of space flight on surface marker expression

NASA Astrophysics Data System (ADS)

Sonnenfeld, G.

1999-01-01

Space flight has been shown to affect expression of several cell surface markers. These markers play important roles in regulation of immune responses, including CD4 and CD8. The studies have involved flight of experimental animals and humans followed by analysis of tissue samples (blood in humans, rats and monkeys, spleen, thymus, lymph nodes and bone marrow in rodents). The degree and direction of the changes induced by space flight have been determined by the conditions of the flight. Also, there may be compartmentalization of the response of surface markers to space flight, with differences in the response of cells isolated from blood and local immune tissue. The same type of compartmentalization was also observed with cell adhesion molecules (integrins). In this case, the expression of integrins from lymph node cells differed from that of splenocytes isolated from rats immediately after space flight. Cell culture studies have indicated that there may be an inhibition in conversion of a precursor cell line to cells exhibiting mature macrophage characteristics after space flight, however, these experiments were limited as a result of technical difficulties. In general, it is clear that space flight results in alterations of cell surface markers. The biological significance of these changes remains to be established.

Green synthesis of silver nanoparticles using Cordia dichotoma fruit extract and its enhanced antibacterial, anti-biofilm and photo catalytic activity

NASA Astrophysics Data System (ADS)

Bharathi, Devaraj; Vasantharaj, Seerangaraj; Bhuvaneshwari, V.

2018-05-01

The present study describes the antibacterial, anti-biofilm and photo catalytic activity of silver nanoparticles synthesized using Cordia dichotoma fruits (Cd-AgNPs) for the first time. The phyto-synthesized Cd-AgNPs were characterized by UV-Visible spectroscopy, Field emission-scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Energy dispersive x-ray spectrometer (EDX), Fourier transform infrared spectroscopy (FT-IR), and x-ray diffraction (XRD). FE-SEM and TEM observation showed that the average size of 2–60 nm with spherical shape of Cd-AgNPs and the presence of phyto-compounds which are responsible for capping and reduction were studied by FT-IR. XRD studies revealed the face-centered cubic structure of Cd-AgNPs. The synthesized Cd-AgNPs showed significant antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, assayed using agar well diffusion method. Phyto-synthesized Cd-AgNPs exhibited more than 90% inhibition of biofilm activity formed by S. aureus and E. coli. Furthermore, photocatalytic degradation of crystal violet (CV) under UV light irradiation using Cd-AgNPs was performed. Synthesized Cd-AgNPs exhibited ∼85% degradation activity for CV. Collectively, our findings suggest that C.dichotoma is a green source for the eco-friendly synthesis of Cd-AgNPs, which further can be used as a novel biocidal agent against bacterial pathogens and a potent photo catalytic agent.

Three-peak standard white organic light-emitting devices for solid-state lighting

NASA Astrophysics Data System (ADS)

Guo, Kunping; Wei, Bin

2014-12-01

Standard white organic light-emitting device (OLED) lighting provides a warm and comfortable atmosphere and shows mild effect on melatonin suppression. A high-efficiency red OLED employing phosphorescent dopant has been investigated. The device generates saturated red emission with Commission Internationale de l'Eclairage (CIE) coordinates of (0.66, 0.34), characterized by a low driving voltage of 3.5 V and high external quantum efficiency of 20.1% at 130 cd m-2. In addition, we have demonstrated a two-peak cold white OLED by combining with a pure blue emitter with the electroluminescent emission of 464 nm, 6, 12-bis{[N-(3,4-dimethylpheyl)-N-(2,4,5-trimethylphenyl)]} chrysene (BmPAC). It was found that the man-made lighting device capable of yielding a relatively stable color emission within the luminance range of 1000-5000 cd m-2. And the chromaticity coordinates, varying from (0.25, 0.21) to (0.23, 0.21). Furthermore, an ultrathin layer of green-light-emitting tris (2-phenylpyridinato)iridium(Ⅲ) Ir(ppy)3 in the host material was introduced to the emissive region for compensating light. By appropriately controlling the layer thickness, the white light OLED achieved good performance of 1280 cd m-2 at 5.0 V and 5150 cd m-2 at 7.0 V, respectively. The CIE coordinates of the emitted light are quite stable at current densities from 759 cd m-2 to 5150 cd m-2, ranging from (0.34, 0.37) to (0.33, 0.33).

Simultaneous determination of L-ascorbic acid, dopamine and uric acid with gold nanoparticles-β-cyclodextrin-graphene-modified electrode by square wave voltammetry.

PubMed

Tian, Xianqing; Cheng, Changming; Yuan, Hongyan; Du, Juan; Xiao, Dan; Xie, Shunping; Choi, Martin M F

2012-05-15

Graphene decorated with gold nanoparticles (AuNPs-β-CD-Gra) has been synthesized by in situ thermal reduction of graphene oxide and HAuCl(4) with β-cyclodextrin (β-CD) under alkaline condition. The AuNPs-β-CD-Gra product was well characterized by infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction. This material was used to fabricate an AuNPs-β-CD-Gra-modified glassy carbon electrode (GCE) which showed excellent electro-oxidation of l-ascorbic acid (AA), dopamine (DA) and uric acid (UA) in 0.10 M NaH(2)PO(4)-HCl buffer solution (pH 2.0) by square wave voltammetry (SWV). Three well-resolved oxidation peaks of AA and DA and UA were obtained. The AuNPs-β-CD-Gra/GCE exhibits linear responses to AA, DA and UA in the ranges 30-2000, 0.5-150 and 0.5-60 μM, respectively. The detection limits (based on S/N=3 and preconcentration time=3.0 min) for AA, DA and UA are 10, 0.15 and 0.21 μM, respectively. The AuNPs-β-CD-Gra/GCE has been successfully applied to determine UA in human urine with satisfactory results. Our work provides a simple, convenient and green route to synthesize AuNPs on Gra which is potentially useful in electroanalysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Androgen resistance in squirrel monkeys (Saimiri spp.).

PubMed

Gross, Katherine L; Westberry, Jenne M; Hubler, Tina R; Sadosky, Patti W; Singh, Ravinder J; Taylor, Robert L; Scammell, Jonathan G

2008-08-01

The goal of this study was to understand the basis for high androgen levels in squirrel monkeys (Saimiri spp.). Mass spectrometry was used to analyze serum testosterone, androstenedione, and dihydrotestosterone of male squirrel monkeys during the nonbreeding (n = 7) and breeding (n = 10) seasons. All hormone levels were elevated compared with those of humans, even during the nonbreeding season; the highest levels occurred during the breeding season. The ratio of testosterone to dihydrotestosterone in squirrel monkeys is high during the breeding season compared to man. Squirrel monkeys may have high testosterone to compensate for inefficient metabolism to dihydrotestosterone. We also investigated whether squirrel monkeys have high androgens to compensate for low-activity androgen receptors (AR). The response to dihydrotestosterone in squirrel monkey cells transfected with AR and AR-responsive reporter plasmids was 4-fold, compared with 28-fold in human cells. This result was not due to overexpression of cellular FKBP51, which causes glucocorticoid and progestin resistance in squirrel monkeys, because overexpression of FKBP51 had no effect on dihydrotestosterone-stimulated reporter activity in a human fibroblast cell line. To test whether the inherently low levels of FKBP52 in squirrel monkeys contribute to androgen insensitivity, squirrel monkey cells were transfected with an AR expression plasmid, an AR-responsive reporter plasmid, and a plasmid expressing FKBP52. Expression of FKBP52 decreased the EC50 or increased the maximal response to dihydrotestosterone. Therefore, the high androgen levels in squirrel monkeys likely compensate for their relatively low 5 alpha-reductase activity during the breeding season and AR insensitivity resulting from low cellular levels of FKBP52.

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata).

PubMed

Ravindranath, N; Ramesh, V; Krishnamurthy, H N; Rao, A J; Moudgal, R N

1992-03-01

To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). Proven fertile male monkeys exhibiting normal testicular function. Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

Occurrence of hemotropic mycoplasmas in non-human primates (Alouatta caraya, Sapajus nigritus and Callithrix jacchus) of southern Brazil.

PubMed

Cubilla, Michelle P; Santos, Leonilda C; de Moraes, Wanderlei; Cubas, Zalmir S; Leutenegger, Christian M; Estrada, Marko; Vieira, Rafael F C; Soares, Maurilio J; Lindsay, LeAnn L; Sykes, Jane E; Biondo, Alexander W

2017-06-01

Hemoplasmas, the erythrocyte-associated mycoplasmas, have been detected in several primates, causing mostly subclinical infection. This study aimed to determine the prevalence of hemoplasma infection in captive and free-ranging monkeys from southern Brazil, as well as factors and hematological abnormalities associated with infection. Blood samples from 40 non-human primates (NHP) were tested for hemoplasmas and coinfections. An overall of 10/40 (25.0%) NHP tested positive for hemoplasmas using PCR-based assays, including 9/14 (64.3%) black howler monkeys (Alouatta caraya) and 1/24 (4.2%) black-horned capuchin (Sapajus nigritus). Infection was not statistically associated with anemia, but wild-born monkeys and male black howler monkeys were more likely to be positive when compared with captive-born animals and female black howler monkeys, respectively. The sequences from the black howler monkey hemoplasma were similar (94% identity) to the squirrel monkey hemoplasma ("Candidatus Mycoplasma kahanei") and were phylogenetically located in a different cluster when compared to the human hemoplasma ("Candidatus Mycoplasma haemohominis"). Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys.

PubMed

Neuringer, Martha; Sandstrom, Marita M; Johnson, Elizabeth J; Snodderly, D Max

2004-09-01

The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment (MP) and may protect the macula from age-related degeneration (AMD). In this study, L or Z was fed to rhesus monkeys reared on xanthophyll-free diets to follow the accumulation of serum carotenoids and MP over time. Eighteen rhesus monkeys were fed xanthophyll-free semipurified diets from birth until 7 to 16 years. The diets of six were then supplemented with pure L and six with pure Z at 3.9 micromol/kg per day (2.2 mg/kg per day) for 24 to 56 weeks. At baseline and 4- to 12-week intervals during supplementation, serum carotenoids were measured by HPLC, and MP density was estimated by two-wavelength reflectometry. Serum carotenoids and MP were also measured in monkeys fed a stock diet. Monkeys fed xanthophyll-free diets had no L or Z in serum and no detectable MP. During supplementation, serum L or Z increased rapidly over the first 4 weeks and from 16 weeks onward maintained similar levels, both several times higher than in stock-diet-fed monkeys. The central peak of MP optical density increased to a relatively steady level by 24 to 32 weeks in both L- and Z-fed groups. Rhesus monkeys fed a stock diet had lower blood concentrations of L than those found in humans and other nonhuman primates. Rhesus monkeys respond to either dietary L or Z supplementation with increases in serum xanthophylls and MP, even after life-long xanthophyll deficiency. These animals provide a potential model to study mechanisms of protection from AMD. Copyright Association for Research in Vision and Ophthalmology

Emergence of Cryptosporidium hominis Monkey Genotype II and Novel Subtype Family Ik in the Squirrel Monkey (Saimiri sciureus) in China.

PubMed

Liu, Xuehan; Xie, Na; Li, Wei; Zhou, Ziyao; Zhong, Zhijun; Shen, Liuhong; Cao, Suizhong; Yu, Xingming; Hu, Yanchuan; Chen, Weigang; Peng, Gangneng

2015-01-01

A single Cryptosporidium isolate from a squirrel monkey with no clinical symptoms was obtained from a zoo in Ya'an city, China, and was genotyped by PCR amplification and DNA sequencing of the small-subunit ribosomal RNA (SSU rRNA), 70-kDa heat shock protein (HSP70), Cryptosporidium oocyst wall protein, and actin genes. This multilocus genetic characterization determined that the isolate was Cryptosporidium hominis, but carried 2, 10, and 6 nucleotide differences in the SSU rRNA, HSP70, and actin loci, respectively, which is comparable to the variations at these loci between C. hominis and the previously reported monkey genotype (2, 3, and 3 nucleotide differences). Phylogenetic studies, based on neighbor-joining and maximum likelihood methods, showed that the isolate identified in the current study had a distinctly discordant taxonomic status, distinct from known C. hominis and also from the monkey genotype, with respect to the three loci. Restriction fragment length polymorphisms of the SSU rRNA gene obtained from this study were similar to those of known C. hominis but clearly differentiated from the monkey genotype. Further subtyping was performed by sequence analysis of the gene encoding the 60-kDa glycoprotein (gp60). Maximum homology of only 88.3% to C. hominis subtype IdA10G4 was observed for the current isolate, and phylogenetic analysis demonstrated that this particular isolate belonged to a novel C. hominis subtype family, IkA7G4. This study is the first to report C. hominis infection in the squirrel monkey and, based on the observed genetic characteristics, confirms a new C. hominis genotype, monkey genotype II. Thus, these results provide novel insights into genotypic variation in C. hominis.

Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy

PubMed Central

Mire, Chad E.; Satterfield, Benjamin A.; Geisbert, Joan B.; Agans, Krystle N.; Borisevich, Viktoriya; Yan, Lianying; Chan, Yee-Peng; Cross, Robert W.; Fenton, Karla A.; Broder, Christopher C.; Geisbert, Thomas W.

2016-01-01

Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh (NiVB). Differences in transmission patterns and mortality rates suggest that NiVB may be more pathogenic than NiVM. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected animals succumbed to infection. Histopathology of lungs and spleens from NiVB-infected AGMs was significantly more severe than NiVM-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM infection, was much shorter in NiVB-infected AGMs. Together, these data show that NiVB is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy. PMID:27484128

Chemical carcinogenesis studies in nonhuman primates

PubMed Central

Takayama, Shozo; Thorgeirsson, Unnur P.; Adamson, Richard H.

2008-01-01

This review covers chemical carcinogenesis studies in nonhuman primates performed by the National Cancer Institute, USA, to provide hitherto unavailable information on their susceptibility to compounds producing carcinogenic effects in rodents. From autopsy records of 401 breeders and untreated controls, incidences of spontaneous malignant tumors were found to be relatively low in cynomolgus (1.9%) and rhesus monkeys (3.8%), but higher in African green monkeys (8%). Various chemical compounds, and in particular 6 antineoplastic agents, 13 food-related compounds including additives and contaminants, 1 pesticide, 5 N-nitroso compounds, 3 heterocyclic amines, and 7 “classical” rodent carcinogens, were tested during the 34 years period, generally at doses 10∼40 times the estimated human exposure. Results were inconclusive in many cases but unequivocal carcinogenicity was demonstrated for IQ, procarbazine, methylnitrosourea and diethylnitrosamine. Furthermore, negative findings for saccharine and cyclamate were in line with results in other species. Thus susceptibility to carcinogens is at least partly shared by nonhuman primates and rodents. PMID:18941297

Cardiac damage induced by 2-amino-3-methyl-imidazo[4,5-f]quinoline in nonhuman primates.

PubMed Central

Thorgeirsson, U P; Farb, A; Virmani, R; Adamson, R H

1994-01-01

The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent hepatocarcinogen in cynomolgus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ, hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights, and no abnormalities were observed upon gross inspection of the hearts. Microscopically, focal myocardial lesions were observed in 8 of 10 monkeys dosed with IQ. Light microscopic abnormalities included myocyte necrosis with or without chronic inflammatory infiltrates, interstitial fibrosis with myocyte hypertrophy or atrophy, and vasculitis. Electron microscopic findings included disruption of the mitochondrial architecture (i.e., mitochondrial swelling and clearing of matrix densities), myofibrillar loss, disorganization of the normal alignment of sarcomeres, and occasional myocytes showing nuclear hypertrophy or peripheral clumping of the nuclear chromatin. There was some correlation between the cumulative dose of IQ and the extent of the myocardial abnormalities. These findings suggest that chronic exposure to IQ can lead to myocardial damage in monkeys. Although focal and not associated with clinical evidence of heart failure, these abnormalities may represent the initial stages of IQ-induced toxic cardiomyopathy. Images Figure 1. A Figure 1. B Figure 1. C Figure 1. D Figure 2. A Figure 2. B Figure 3. A Figure 3. B Figure 3. C Figure 3. D Figure 4. A Figure 4. B Figure 5. A Figure 5. B PMID:8033851

Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats

PubMed Central

Brunner, Valérie; Maynadier, Bernadette; Chen, Laishun; Roques, Louise; Hude, Isabelle; Séguier, Sébastien; Barthe, Laurence; Hermann, Philippe

2015-01-01

Levomilnacipran is approved in the US for the treatment of major depressive disorder in adults. We characterized the metabolic profile of levomilnacipran in humans, monkeys, and rats after oral administration of [14C]-levomilnacipran. In vitro binding of levomilnacipran to human plasma proteins was also studied. Unchanged levomilnacipran was the major circulating compound after dosing in all species. Within 12 hours of dosing in humans, levomilnacipran accounted for 52.9% of total plasma radioactivity; the circulating metabolites N-desethyl levomilnacipran N-carbamoyl glucuronide, N-desethyl levomilnacipran, and levomilnacipran N-carbamoyl glucuronide accounted for 11.3%, 7.5%, and 5.6%, respectively. Similar results were seen in monkeys. N-Desethyl levomilnacipran and p-hydroxy levomilnacipran were the main circulating metabolites in rats. Mass balance results indicated that renal excretion was the major route of elimination with 58.4%, 35.5%, and 40.2% of total radioactivity being excreted as unchanged levomilnacipran in humans, monkeys, and rats, respectively. N-Desethyl levomilnacipran was detected in human, monkey, and rat urine (18.2%, 12.4%, and 7.9% of administered dose, respectively). Human and monkey urine contained measurable quantities of levomilnacipran glucuronide (3.8% and 4.1% of administered dose, respectively) and N-desethyl levomilnacipran glucuronide (3.2% and 2.3% of administered dose, respectively); these metabolites were not detected in rat urine. The metabolites p-hydroxy levomilnacipran and p-hydroxy levomilnacipran glucuronide were detected in human urine (≤1.2% of administered dose), and p-hydroxy levomilnacipran glucuronide was found in rat urine (4% of administered dose). None of the metabolites were pharmacologically active. Levomilnacipran was widely distributed with low plasma protein binding (22%). PMID:26150694

Characterization and phylogenetic epitope mapping of CD38 ADPR cyclase in the cynomolgus macaque

PubMed Central

Ferrero, Enza; Orciani, Monia; Vacca, Paola; Ortolan, Erika; Crovella, Sergio; Titti, Fausto; Saccucci, Franca; Malavasi, Fabio

2004-01-01

Background The CD38 transmembrane glycoprotein is an ADP-ribosyl cyclase that moonlights as a receptor in cells of the immune system. Both functions are independently implicated in numerous areas related to human health. This study originated from an inherent interest in studying CD38 in the cynomolgus monkey (Macaca fascicularis), a species closely related to humans that also represents a cogent animal model for the biomedical analysis of CD38. Results A cDNA was isolated from cynomolgus macaque peripheral blood leukocytes and is predicted to encode a type II membrane protein of 301 amino acids with 92% identity to human CD38. Both RT-PCR-mediated cDNA cloning and genomic DNA PCR surveying were possible with heterologous human CD38 primers, demonstrating the striking conservation of CD38 in these primates. Transfection of the cDNA coincided with: (i) surface expression of cynomolgus macaque CD38 by immunofluorescence; (ii) detection of ~42 and 84 kDa proteins by Western blot and (iii) the appearance of ecto-enzymatic activity. Monoclonal antibodies were raised against the cynomolgus CD38 ectodomain and were either species-specific or cross-reactive with human CD38, in which case they were directed against a common disulfide-requiring conformational epitope that was mapped to the C-terminal disulfide loop. Conclusion This multi-faceted characterization of CD38 from cynomolgus macaque demonstrates its high genetic and biochemical similarities with human CD38 while the immunological comparison adds new insights into the dominant epitopes of the primate CD38 ectodomain. These results open new prospects for the biomedical and pharmacological investigations of this receptor-enzyme. PMID:15383153

Identification of new diterpene esters from green Arabica coffee beans, and their platelet aggregation accelerating activities.

PubMed

Wang, Xia; Meng, QianQian; Peng, XingRong; Hu, GuiLin; Qiu, MingHua

2018-10-15

Eight new ent-kaurane diterpene fatty acid esters, namely caffarolides A-H (1-8), were isolated from green beans of Coffea arabica. Their chemical structures were confirmed by extensive spectroscopic analysis including 1D, 2D NMR (HSQC, HMBC, 1 H- 1 H COSY, and ROESY), HRMS, IR and CD spectra and by GC-FID analysis. Interestingly, the diterpene moiety of these new compounds first occurred in genus Coffea. All the isolates were evaluated for platelet aggregation activity in vitro. As the results, caffarolides C, D and F (3, 4 and 6) showed induction effect for platelet aggregation and the possible structure-activity relationships have been discussed briefly. Copyright © 2018 Elsevier Ltd. All rights reserved.

Photostable and Low-Toxic Yellow-Green Carbon Dots for Highly Selective Detection of Explosive 2,4,6-Trinitrophenol Based on the Dual Electron Transfer Mechanism.

PubMed

Ju, Bo; Wang, Yi; Zhang, Yu-Mo; Zhang, Ting; Liu, Zhihe; Li, Minjie; Xiao-An Zhang, Sean

2018-04-18

Advances in the development of fluorescent carbon dots (CDs) for detecting nitro-explosives have attracted great interest. However, developing long-wavelength luminescence CDs for highly selective determination of 2,4,6-trinitrophenol (TNP) and getting insight into the detection mechanism remain further to be investigated. Here, excitation-independent yellow-green emission CDs with good photostability and low biotoxicity were introduced for detecting TNP selectively. Then, two types of electron transfer (ET) processes including hydrogen-bond interaction-assisted ET and proton transfer-assisted ET are suggested to be responsible for their photophysical behavior. Finally, the visual detection of TNP has been successfully developed by a CD-based indicator paper. The facile, highly sensitive, and selective detection for TNP in both of a solution and a solid phase makes CDs potentially useful in environmental sensor applications.

The reactivity of plasma phospholipids with lecithin:cholesterol acyltransferase is decreased in fish oil-fed monkeys.

PubMed

Parks, J S; Bullock, B C; Rudel, L L

1989-02-15

The size of low density lipoproteins (LDL) is strongly correlated with LDL cholesteryl ester (CE) content and coronary artery atherosclerosis in monkeys fed cholesterol and saturated fat. African green monkeys fed 11% (weight) fish oil diets have smaller LDL and less CE per LDL particle than lard-fed animals. We hypothesized that this might be due to a lower plasma lecithin:cholesterol acyltransferase (LCAT) activity in fish oil-fed animals. Using recombinant particles made of egg yolk lecithin-[14C]cholesterol-apoA-I as exogenous substrate, we found no difference in plasma LCAT activity (27 versus 28 nmol CE formed per h/ml) of fish oil- versus lard-fed animals, respectively; furthermore, no diet-induced difference in immunodetectable LCAT was found. However, plasma phospholipids from fish oil-fed animals were over 4-fold enriched in n-3 fatty acids in the sn-2 position compared to those of lard-fed animals. Additionally, the proportion of n-3 fatty acid-containing CE products formed by LCAT, relative to the available n-3 fatty acid in the sn-2 position of phospholipids, was less than one-tenth of that for linoleic acid. The overall rate of LCAT-catalyzed CE formation with phospholipid substrates from fish oil-fed animals was lower (5-50%) than with phospholipid substrates from lard-fed animals. These data show that n-3 fatty acids in phospholipids are not readily utilized by LCAT for formation of CE; rather, LCAT preferentially utilizes linoleic acid for CE formation. The amount of linoleic acid in the sn-2 position of plasma phospholipids is reduced and replaced with n-3 fatty acids in fish oil-fed animals. As a result, LCAT-catalyzed plasma CE formation in vivo is likely reduced in fish oil-fed animals contributing to the decreased cholesteryl ester content and smaller size of LDL particles in the animals of this diet group.

T-Cell Tropism of Simian Varicella Virus during Primary Infection

PubMed Central

Ouwendijk, Werner J. D.; Mahalingam, Ravi; de Swart, Rik L.; Haagmans, Bart L.; van Amerongen, Geert; Getu, Sarah; Gilden, Don; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.

2013-01-01

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. PMID:23675304

Altered expression of glial markers, chemokines, and opioid receptors in the spinal cord of type 2 diabetic monkeys.

PubMed

Kiguchi, Norikazu; Ding, Huiping; Peters, Christopher M; Kock, Nancy D; Kishioka, Shiroh; Cline, J Mark; Wagner, Janice D; Ko, Mei-Chuan

2017-01-01

Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6). By using RT-qPCR, we found that mRNA expression levels of both GFAP and IBA1 were up-regulated in the spinal dorsal horn (SDH) of diabetic monkeys compared with non-diabetic monkeys. Among all chemokines, expression levels of three chemokine ligand-receptor systems, i.e., CCL2-CCR2, CCL3-CCR1/5, and CCL4-CCR5, were up-regulated in the SDH of diabetic monkeys. Moreover, in the SDH, seven additional chemokine receptors, i.e., CCR4, CCR6, CCR8, CCR10, CXCR3, CXCR5, and CXCR6, were also up-regulated in diabetic monkeys. In contrast, expression levels of MOP, KOP, and DOP, but not NOP receptors, were down-regulated in the SDH of diabetic monkeys, and the thalamus had fewer changes in the glial markers, chemokines and opioids. These findings indicate that neuroinflammation, manifested as glial activation and simultaneous up-regulation of multiple chemokine ligands and receptors, seems to be permanent in type 2 diabetic monkeys. As chemokines and opioids are important pain modulators, this first-in-primate study provides a translational bridge for determining the functional efficacy of spinal drugs targeting their signaling cascades. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and structural characterization of magnetic cadmium sulfide-cobalt ferrite nanocomposite, and study of its activity for dyes degradation under ultrasound

NASA Astrophysics Data System (ADS)

Farhadi, Saeed; Siadatnasab, Firouzeh

2016-11-01

Cadmium sulfide-cobalt ferrite (CdS/CFO) nanocomposite was easily synthesized by one-step hydrothermal decomposition of cadmium diethyldithiocarbamate complex on the CoFe2O4 nanoparticles at 200 °C. Spectroscopic techniques of powder X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), UV-visible spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), Brunauer-Emmett-Teller (BET), and magnetic measurements were applied for characterizing the structure and morphology of the product. The results of FT-IR, XRD and EDX indicated that the CdS/CFO was highly pure. SEM and TEM results revealed that the CdS/CFO nanocomposite was formed from nearly uniform and sphere-like nanoparticles with the size of approximately 20 nm. The UV-vis absorption spectrum of the CdS/CFO nanocomposite showed the band gap of 2.21 eV, which made it suitable for sono-/photo catalytic purposes. By using the obtained CdS/CFO nanocomposite, an ultrasound-assisted advanced oxidation process (AOP) has been developed for catalytic degradation of methylene blue (MB), Rhodamine B (RhB), and methyl orange (MO)) in the presence of H2O2 as a green oxidant. CdS/CFO nanocomposite exhibited excellent sonocatalytic activity, so that, dyes were completely degraded in less than 10 min. The influences of crucial factors such as the H2O2 amount and catalyst dosage on the degradation efficiency were evaluated. The as-prepared CdS/CFO nanocomposite exhibited higher catalytic activity than pure CdS nanoparticles. Moreover, the magnetic property of CoFe2O4 made the nanocomposite recyclable.

Cd2+ Toxicity to a Green Alga Chlamydomonas reinhardtii as Influenced by Its Adsorption on TiO2 Engineered Nanoparticles

PubMed Central

Yang, Wei-Wan; Miao, Ai-Jun; Yang, Liu-Yan

2012-01-01

In the present study, Cd2+ adsorption on polyacrylate-coated TiO2 engineered nanoparticles (TiO2-ENs) and its effect on the bioavailability as well as toxicity of Cd2+ to a green alga Chlamydomonas reinhardtii were investigated. TiO2-ENs could be well dispersed in the experimental medium and their pHpzc is approximately 2. There was a quick adsorption of Cd2+ on TiO2-ENs and a steady state was reached within 30 min. A pseudo-first order kinetics was found for the time-related changes in the amount of Cd2+ complexed with TiO2-ENs. At equilibrium, Cd2+ adsorption followed the Langmuir isotherm with the maximum binding capacity 31.9, 177.1, and 242.2 mg/g when the TiO2-EN concentration was 1, 10, and 100 mg/l, respectively. On the other hand, Cd2+ toxicity was alleviated in the presence of TiO2-ENs. Algal growth was less suppressed in treatments with comparable total Cd2+ concentration but more TiO2-ENs. However, such toxicity difference disappeared and all the data points could be fitted to a single Logistic dose-response curve when cell growth inhibition was plotted against the free Cd2+ concentration. No detectable amount of TiO2-ENs was found to be associated with the algal cells. Therefore, TiO2-ENs could reduce the free Cd2+ concentration in the toxicity media, which further lowered its bioavailability and toxicity to C. reinhardtii. PMID:22403644

Do capuchin monkeys (Cebus apella) diagnose causal relations in the absence of a direct reward?

PubMed

Edwards, Brian J; Rottman, Benjamin M; Shankar, Maya; Betzler, Riana; Chituc, Vladimir; Rodriguez, Ricardo; Silva, Liara; Wibecan, Leah; Widness, Jane; Santos, Laurie R

2014-01-01

We adapted a method from developmental psychology to explore whether capuchin monkeys (Cebus apella) would place objects on a "blicket detector" machine to diagnose causal relations in the absence of a direct reward. Across five experiments, monkeys could place different objects on the machine and obtain evidence about the objects' causal properties based on whether each object "activated" the machine. In Experiments 1-3, monkeys received both audiovisual cues and a food reward whenever the machine activated. In these experiments, monkeys spontaneously placed objects on the machine and succeeded at discriminating various patterns of statistical evidence. In Experiments 4 and 5, we modified the procedure so that in the learning trials, monkeys received the audiovisual cues when the machine activated, but did not receive a food reward. In these experiments, monkeys failed to test novel objects in the absence of an immediate food reward, even when doing so could provide critical information about how to obtain a reward in future test trials in which the food reward delivery device was reattached. The present studies suggest that the gap between human and animal causal cognition may be in part a gap of motivation. Specifically, we propose that monkey causal learning is motivated by the desire to obtain a direct reward, and that unlike humans, monkeys do not engage in learning for learning's sake.

Do Capuchin Monkeys (Cebus apella) Diagnose Causal Relations in the Absence of a Direct Reward?

PubMed Central

Edwards, Brian J.; Rottman, Benjamin M.; Shankar, Maya; Betzler, Riana; Chituc, Vladimir; Rodriguez, Ricardo; Silva, Liara; Wibecan, Leah; Widness, Jane; Santos, Laurie R.

2014-01-01

We adapted a method from developmental psychology [1] to explore whether capuchin monkeys (Cebus apella) would place objects on a “blicket detector” machine to diagnose causal relations in the absence of a direct reward. Across five experiments, monkeys could place different objects on the machine and obtain evidence about the objects’ causal properties based on whether each object “activated” the machine. In Experiments 1–3, monkeys received both audiovisual cues and a food reward whenever the machine activated. In these experiments, monkeys spontaneously placed objects on the machine and succeeded at discriminating various patterns of statistical evidence. In Experiments 4 and 5, we modified the procedure so that in the learning trials, monkeys received the audiovisual cues when the machine activated, but did not receive a food reward. In these experiments, monkeys failed to test novel objects in the absence of an immediate food reward, even when doing so could provide critical information about how to obtain a reward in future test trials in which the food reward delivery device was reattached. The present studies suggest that the gap between human and animal causal cognition may be in part a gap of motivation. Specifically, we propose that monkey causal learning is motivated by the desire to obtain a direct reward, and that unlike humans, monkeys do not engage in learning for learning’s sake. PMID:24586347

Antigenic and biologic characteristics of Venezuelan encephalitis virus strains including a possible new subtype, isolated from the Amazon region of Peru in 1971.

PubMed

Scherer, W F; Anderson, K

1975-04-01

Nine strains of Venezuelan encephalitis (VE) virus isolated from the Amazon region of Peru in 1971 were identified as antigenic subtype I based on plaque-reduction neutralization tests with four and 20 units of antibody. A tenth strain, 71D1252, was possibly a new subtype, but was related to subtypes I and III. Hemagglutinins of each strain made from infected mouse brains had optimals pHs of 6.2 and 6.4. Nine strains were pathogenic for adult hamsters and adult mice, but strain 71D1252 inapparently infected some adult hamsters and mice inoculated peripherally. Plaques of nine strains in Vero African green monkey kidney cell cultures were intermediate in size between representative epizootic and enzootic strains, but plaques of strain 71D1252 were small like epizootic strains.

Characterization of Novel Simian Immunodeficiency Viruses from Red-Capped Mangabeys from Nigeria (SIVrcmNG409 and -NG411)

PubMed Central

Beer, Brigitte E.; Foley, Brian T.; Kuiken, Carla L.; Tooze, Zena; Goeken, Robert M.; Brown, Charles R.; Hu, Jinjie; Claire, Marisa St.; Korber, Bette T.; Hirsch, Vanessa M.

2001-01-01

Two novel simian immunodeficiency virus (SIV) strains from wild-caught red-capped mangabeys (Cercocebus torquatus torquatus) from Nigeria were characterized. Sequence analysis of the fully sequenced SIV strain rcmNG411 (SIVrcmNG411) and gag and pol sequence of SIVrcmNG409 revealed that they were genetically most closely related to the recently characterized SIVrcm from Gabon (SIVrcmGB1). Thus, red-capped mangabeys from distant geographic locations harbor a common lineage of SIV. SIVrcmNG411 carried a vpx gene in addition to vpr, suggesting a common evolutionary ancestor with SIVsm (from sooty mangabeys). However, SIVrcm was only marginally closer to SIVsm in that region than to any of the other lentiviruses. SIVrcm showed the highest similarity in pol with SIVdrl, isolated from a drill, a primate that is phylogenetically distinct from mangabey monkeys, and clustered with other primate lentiviruses (primarily SIVcpz [from chimpanzees] and SIVagmSab [from African green monkeys]) discordantly in different regions of the genome, suggesting a history of recombination. Despite the genetic relationship to SIVcpz in the pol gene, SIVrcmNG411 did not replicate in chimpanzee peripheral blood mononuclear cells (PBMC), although two other viruses unrelated to SIVcpz, SIVmndGB1 (from mandrills) and SIVlhoest (from L'Hoest monkeys), were able to grow in chimpanzee PBMC. The CCR5 24-bp deletion previously described in red-capped mangabeys from Gabon was also observed in Nigerian red-capped mangabeys, and SIVrcmNG411, like SIVrcmGB1, used CCR2B and STRL33 as coreceptors for virus entry. SIVrcm, SIVsm, SIVmndGB1, and all four SIVlhoest isolates but not SIVsun (from sun-tailed monkeys) replicated efficiently in human PBMC, suggesting that the ability to infect the human host can vary within one lineage. PMID:11711592

Case Series With Histopathologic and Radiographic Analyses Following Failure of Fresh Osteochondral Allografts of the Talus.

PubMed

Pomajzl, Ryan Joseph; Baker, Erin Ann; Baker, Kevin Charles; Fleischer, Mackenzie Marie; Salisbury, Meagan R; Phillips, Dylan M; Fortin, Paul Thomas

2016-09-01

Fresh osteochondral allografting of the talus is one treatment option for large chondral defects. Following positive early term results, failure rates of up to 35% have been reported. A retrieval study was performed to characterize failed talar allografts. Failed fresh osteochondral allografts of the talus were retrieved on revision. Cases of deep infection were excluded. After tissue fixation, samples were decalcified, embedded, and stained with Safranin-O/Fast Green, osteocalcin, tumor necrosis factor alpha (TNF-α), CD4, CD8, and CD68. Slides were graded according to the modified Mankin scoring system or severity scale. Medical record review was performed. Eight allografts (7 patients) were retrieved from patients, following an average term of implantation of 31 months (range, 12-58). There were 3 types of allografts in this series (hemidome, n=5; segmental, n=2; bipolar, n=1). Reasons for transplantation were post-traumatic arthritis or osteonecrosis; reasons for revision were graft failure/collapse, nonunion, progressive arthritis, and/or pain. Prior to revision, all grafts exhibited collapse and subchondral lucencies. At the graft host interface, Safranin-O staining demonstrated substantial loss of sulfated glycosaminoglycans, Osteocalcin immunostaning was nearly absent, CD68 (indicating osteoclast activity) was predominantly exhibited, and CD4+ helper T cells as well as CD8+ cytotoxic T cells and NK cells-cell types commonly implicated in allogeneic organ transplant rejection-were found in high concentrations. TNF-α was present throughout the graft. A histopathologic analysis of 8 retrieved, failed talar allografts was performed. Graft failure appeared to be primarily biologic, with an extensive loss of viable cartilaginous and osseous tissue at the graft-host interface. This study provides the first evidence of a potential CD4+ and CD8+ lymphocyte-mediated failure mechanism in fresh osteochondral allografts that were revised following collapse. Level IV, case series. © The Author(s) 2016.

African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates

PubMed Central

Matsuoka, Yumiko; Suguitan, Amorsolo; Orandle, Marlene; Paskel, Myeisha; Boonnak, Kobporn; Gardner, Donald J.; Feldmann, Friederike; Feldmann, Heinz; Marino, Michael; Jin, Hong; Kemble, George

2014-01-01

ABSTRACT Live attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication of wt and ca viruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of the wt viruses replicated efficiently, while replication of the ca vaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2 ca vaccines. Protection from wt virus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication of ca vaccine candidates. IMPORTANCE Ferrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we observed significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a nonhuman primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza virus vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans and that AGMs can be useful for evaluation of the protective efficacy of pLAIV. PMID:24807726

Versatile benzimidazole/triphenylamine hybrids: efficient nondoped deep-blue electroluminescence and good host materials for phosphorescent emitters.

PubMed

Gong, Shaolong; Zhao, Yongbiao; Wang, Meng; Yang, Chuluo; Zhong, Cheng; Qin, Jingui; Ma, Dongge

2010-09-03

Two new bipolar compounds, N,N,N',N'-tetraphenyl-5'-(1-phenyl-1H-benzimidazol-2-yl)-1,1':3',1''-terphenyl-4,4''-diamine (1) and N,N,N',N'-tetraphenyl-5'-(1-phenyl-1H-benzimidazol-2-yl)-1,1':3',1''-terphenyl-3,3''-diamine (2), were synthesized and characterized, and their thermal, photophysical, and electrochemical properties were investigated. Compounds 1 and 2 possess good thermal stability with high glass-transition temperatures of 109-129 degrees C and thermal decomposition temperatures of 501-531 degrees C. The fluorescence quantum yield of 1 (0.52) is higher than that of 2 (0.16), which could be attributed to greater pi conjugation between the donor and acceptor moieties. A nondoped deep-blue fluorescent organic light-emitting diode (OLED) using 1 as the blue emitter displays high performance, with a maximum current efficiency of 2.2 cd A(-1) and a maximum external efficiency of 2.9 % at the CIE coordinates of (0.17, 0.07) that are very close to the National Television System Committee's blue standard (0.15, 0.07). Electrophosphorescent devices using the two compounds as host materials for green and red phosphor emitters show high efficiencies. The best performance of a green phosphorescent device was achieved using 2 as the host, with a maximum current efficiency of 64.3 cd A(-1) and a maximum power efficiency of 68.3 lm W(-1); whereas the best performance of a red phosphorescent device was achieved using 1 as the host, with a maximum current efficiency of 11.5 cd A(-1), and a maximum power efficiency of 9.8 lm W(-1). The relationship between the molecular structures and optoelectronic properties are discussed.

Suppurative bite wound by repetitive aggression of dominance hierarchy during group housing in rhesus monkeys.

PubMed

Choi, Yunjung; Ahn, Kyung-Ha; Lee, Jae-Il

2014-12-01

Group formation of rhesus monkeys, often leads to victims of repeated attacks by the high ranking animal. We reported a case of an injured middle ranking monkey from repetitive and persistent aggression. 4-male rhesus group was formed by a rapid group formation strategy 2 years ago. One monkey in the group suddenly showed depressive and reluctant movement. Physical examination revealed multiple bite wounds and scars in the dorsal skin. Overall increased opacity of the dorsal soft tissue and some free air was observed on radiographic examination. An unidentified anaerobic gram negative bacillus was isolated from the bacterial culture. Reconstructive surgery was performed and in consequence, the wound was clearly reconstructed one week later. Eventually, the afflicted monkey was separated and housed apart from the hierarchical group. This case report indicate that group formation in rhesus monkeys is essentially required sufficient time and stages, as well as more attention and a progressive contact program to reduce animal stress and fatal accidents.

Rhesus monkeys (Macaca mulatta) remember agency information from past events and integrate this knowledge with spatial and temporal features in working memory.

PubMed

Hoffman, Megan L; Beran, Michael J; Washburn, David A

2018-01-01

The purpose of the present study was to examine whether rhesus monkeys remember information about their own agency-along with spatial, temporal and contextual properties-from a previously experienced event. In Experiment 1, rhesus monkeys (n = 4) used symbols to reliably indicate whether they had performed or observed an event on a computer screen. In Experiment 2, naïve and experienced monkeys (n = 8) reported agency information when stringent controls for perceptual and proprioceptive cues were included. In Experiment 3, five of the monkeys completed a task in which they reported agency information along with spatial and temporal features of events. Two monkeys performed this agency discrimination when they could not anticipate which memory test they would receive. There was also evidence that these features were integrated in memory. Implications of this research are discussed in relation to working memory, episodic memory and self-awareness in nonhuman animals.

Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1

PubMed Central

Dagnino, Bruno; Gariel-Mathis, Marie-Alice

2014-01-01

Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness. We investigated the interactions between the primary visual cortex (V1) and area V4 by applying microstimulation in both cortical areas at various delays. We report that the monkeys detected the phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation did not influence V1 phosphene detection thresholds. A second experiment examined the influence of V4 microstimulation on the monkeys' ability to detect the dimming of one of three peripheral visual stimuli. Again, microstimulation of a group of V4 neurons failed to modulate the monkeys' perception of a stimulus in their receptive field. We conclude that conditions exist where microstimulation of area V4 has only a limited influence on visual perception. PMID:25392172

Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1.

PubMed

Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Roelfsema, Pieter R

2015-02-01

Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness. We investigated the interactions between the primary visual cortex (V1) and area V4 by applying microstimulation in both cortical areas at various delays. We report that the monkeys detected the phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation did not influence V1 phosphene detection thresholds. A second experiment examined the influence of V4 microstimulation on the monkeys' ability to detect the dimming of one of three peripheral visual stimuli. Again, microstimulation of a group of V4 neurons failed to modulate the monkeys' perception of a stimulus in their receptive field. We conclude that conditions exist where microstimulation of area V4 has only a limited influence on visual perception. Copyright © 2015 the American Physiological Society.

Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Jinghua; Eng, J.; Yalow, R.S.

1990-12-01

It was reported two decades ago that insulin was not detectable in the glucose-stimulated state in Saimiri sciurea, the New World squirrel monkey, by a radioimmunoassay system developed with guinea pig anti-pork insulin antibody and labeled park insulin. With the same system, reasonable levels were observed in rhesus monkeys and chimpanzees. This suggested that New World monkeys, like the New World hystricomorph rodents such as the guinea pig and the coypu, might have insulins whose sequences differ markedly from those of Old World mammals. In this report the authors describe the purification and amino acid sequences of squirrel monkey insulinmore » and glucagon. They demonstrate that the substitutions at B29, B27, A2, A4, and A17 of squirrel monkey insulin are identical with those previously found in another New World primate, the owl monkey (Aotus trivirgatus). The immunologic cross-reactivity of this insulin in their immunoassay system is only a few percent of that of human insulin. It appears that the peptides of the New World monkeys have diverged less from those of the Old World mammals than have those of the New World hystricomorph rodents. The striking improvements in peptide purification and sequencing have the potential for adding new information concerning the evolutionary divergence of species.« less

Muscle Feasibility for Cosmos Rhesus

NASA Technical Reports Server (NTRS)

Edgerton, V. Reggie (Principal Investigator); Roland, Roy R.; Hodgson, John A.

1994-01-01

The following tasks were proposed for the Cosmos project: 1) Complete recordings of all preflight candidates during performance of a foot pedal motor control task while in the space capsule mock-up. 2) Complete recordings of all preflight candidates during locomotion and postural tasks. 3) Complete recordings of 24-hour spontaneous cage activity in the two flight monkeys before and after flight and of at least three control (non-flight) monkeys after the flight has been completed. 4) Complete recordings of the foot pedal and motor control tasks during flight and postflight as scheduled. 5) Complete recordings of the vertical drop test pre, during and postflight for the two flight and three control monkeys. 6) Complete recordings of locomotion and posture tests of the two flight monkeys postflight. 7) Complete recordings of locomotion and postural tests of at least three control (non-flight) monkeys during the postflight period. 8) Recalibrate buckles of the two flight and of at least three control monkeys postflight. 9) Complete analysis of the 24 hour EMG recordings of all monkeys. 10) Complete analysis of the foot pedal, locomotor and postural motor control tasks for the two flight and three control monkeys. It was proposed that efforts in the first postflight year be concentrated on the two flight animals and three postflight animals.

Immunization with Recombinant Helicobacter pylori Urease in Specific-Pathogen-Free Rhesus Monkeys (Macaca mulatta)

PubMed Central

Solnick, Jay V.; Canfield, Don R.; Hansen, Lori M.; Torabian, Sima Z.

2000-01-01

Immunization with urease can protect mice from challenge with Helicobacter pylori, though results vary depending on the particular vaccine, challenge strain, and method of evaluation. Unlike mice, rhesus monkeys are naturally colonized with H. pylori and so may provide a better estimate of vaccine efficacy in humans. The purpose of this study was to examine the effectiveness of H. pylori urease as a vaccine in specific-pathogen (H. pylori)-free rhesus monkeys. Monkeys raised from birth and documented to be free of H. pylori were vaccinated with orogastric (n = 4) or intramuscular (n = 5) urease. Two control monkeys were sham vaccinated. All monkeys were challenged with a rhesus monkey-derived strain of H. pylori, and the effects of vaccination were evaluated by use of quantitative cultures of gastric tissue, histology, and measurement of serum immunoglobulin G (IgG) and salivary IgA. Despite a humoral immune response, all monkeys were infected after H. pylori challenge, and there were no differences in the density of colonization. Immunization with urease therefore does not fully protect against challenge with H. pylori. An effective vaccine to prevent H. pylori infection will require different or more likely additional antigens, as well as improvements in the stimulation of the host immune response. PMID:10768944

The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

PubMed

Obata, Toshio; Aomine, Masahiro

The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

Chronic Nicotine Treatment Increases nAChRs and Microglial Expression in Monkey Substantia Nigra after Nigrostriatal Damage

PubMed Central

Campos, Carla; Parameswaran, Neeraja; William Langston, J.; Michael McIntosh, J.; Yeluashvili, Michael

2010-01-01

Our previous work had shown that long-term nicotine administration improved dopaminergic markers and nicotinic receptors (nAChRs) in the striatum of monkeys with nigrostriatal damage. The present experiments were done to determine whether nicotine treatment also led to changes in the substantia nigra, the region containing dopaminergic cell bodies. Monkeys were chronically treated with nicotine in the drinking water for 6 months after which they were injected with low dose MPTP for a further 6-month period. Nicotine was administered until the monkeys were euthanized 2 months after the last MPTP injection. Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys. However, nicotine administration did lead to a greater increase in α3/α6β2* and α4β2* nAChRs in lesioned monkeys compared to controls. Nicotine also significantly elevated microglia and reduced the number of extracellular neuromelanin deposits in the substantia nigra of MPTP-lesioned monkeys. These findings indicate that long-term nicotine treatment modulates expression of several molecular measures in monkey substantia nigra that may result in an improvement in nigral integrity and/or function. These observations may have therapeutic implications for Parkinson’s disease. PMID:19685015

Monkey Viperin Restricts Porcine Reproductive and Respiratory Syndrome Virus Replication.

PubMed

Fang, Jianyu; Wang, Haiyan; Bai, Juan; Zhang, Qiaoya; Li, Yufeng; Liu, Fei; Jiang, Ping

2016-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen which causes huge economic damage globally in the swine industry. Current vaccination strategies provide only limited protection against PRRSV infection. Viperin is an interferon (IFN) stimulated protein that inhibits some virus infections via IFN-dependent or IFN-independent pathways. However, the role of viperin in PRRSV infection is not well understood. In this study, we cloned the full-length monkey viperin (mViperin) complementary DNA (cDNA) from IFN-α-treated African green monkey Marc-145 cells. It was found that the mViperin is up-regulated following PRRSV infection in Marc-145 cells along with elevated IRF-1 gene levels. IFN-α induced mViperin expression in a dose- and time-dependent manner and strongly inhibits PRRSV replication in Marc-145 cells. Overexpression of mViperin suppresses PRRSV replication by blocking the early steps of PRRSV entry and genome replication and translation but not inhibiting assembly and release. And mViperin co-localized with PRRSV GP5 and N protein, but only interacted with N protein in distinct cytoplasmic loci. Furthermore, it was found that the 13-16 amino acids of mViperin were essential for inhibiting PRRSV replication, by disrupting the distribution of mViperin protein from the granular distribution to a homogeneous distribution in the cytoplasm. These results could be helpful in the future development of novel antiviral therapies against PRRSV infection.

Segregation of short-wavelength-sensitive (S) cone signals in the macaque dorsal lateral geniculate nucleus

PubMed Central

Roy, Sujata; Jayakumar, Jaikishan; Martin, Paul R; Dreher, Bogdan; Saalmann, Yuri B; Hu, Daping; Vidyasagar, Trichur R

2009-01-01

An important problem in the study of the mammalian visual system is whether functionally different retinal ganglion cell types are anatomically segregated further up along the central visual pathway. It was previously demonstrated that, in a New World diurnal monkey (marmoset), the neurones carrying signals from the short-wavelength-sensitive (S) cones [blue–yellow (B/Y)-opponent cells] are predominantly located in the koniocellular layers of the dorsal lateral geniculate nucleus (LGN), whereas the red–green (R/G)-opponent cells carrying signals from the medium- and long-wavelength-sensitive cones are segregated in the parvocellular layers. Here, we used extracellular single-unit recordings followed by histological reconstruction to investigate the distribution of color-selective cells in the LGN of the macaque, an Old World diurnal monkey. Cells were classified using cone-isolating stimuli to identify their cone inputs. Our results indicate that the majority of cells carrying signals from S-cones are located either in the koniocellular layers or in the ‘koniocellular bridges’ that fully or partially span the parvocellular layers. By contrast, the R/G-opponent cells are located in the parvocellular layers. We conclude that anatomical segregation of B/Y- and R/G-opponent afferent signals for color vision is common to the LGNs of New World and Old World diurnal monkeys. PMID:19821840

Nocardioides albertanoniae sp. nov., isolated from Roman catacombs.

PubMed

Alias-Villegas, Cynthia; Jurado, Valme; Laiz, Leonila; Miller, Ana Z; Saiz-Jimenez, Cesareo

2013-04-01

A Gram-reaction-positive, aerobic, non-spore-forming, rod- or coccoid-shaped, strain, CD40127(T), was isolated from a green biofilm covering the wall of the Domitilla Catacombs in Rome, Italy. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CD40127(T) belongs to the genus Nocardioides, closely related to Nocardioides luteus DSM 43366(T) and Nocardioides albus DSM 43109(T) with 98.86 % and 98.01 % similarity values, respectively. Strain CD40127(T) exhibited 16S rRNA gene sequence similarity values below 96.29 % with the rest of the species of the genus Nocardioides. The G+C content of the genomic DNA was 69.7 mol%. The predominant fatty acid was iso-C16 : 0 and the major menaquinone was MK-8(H4) in accordance with the phenotypes of other species of the genus Nocardioides. A polyphasic approach using physiological tests, fatty acid profiles, DNA base ratios and DNA-DNA hybridization showed that isolate CD40127(T) represents a novel species within the genus Nocardioides, for which the name Nocardioides albertanoniae is proposed. The type strain is CD40127(T) ( = DSM 25218(T) = CECT 8014(T)).

Identification of two novel pigment precursors and a reddish-purple pigment involved in the blue-green discoloration of onion and garlic.

PubMed

Imai, Shinsuke; Akita, Kaori; Tomotake, Muneaki; Sawada, Hiroshi

2006-02-08

By using a model reaction system representing blue-green discoloration that occurs when purees of onion (Allium cepa L.) and garlic (Allium sativum L.) are mixed, we isolated two pigment precursors (PPs) and a reddish-purple pigment (PUR-1) and determined their chemical structures. PPs were isolated from a heat-treated solution containing color developer (CD) and either l-valine or l-alanine, and their structures were determined as 2-(3,4-dimethylpyrrolyl)-3-methylbutanoic acid (PP-Val), and 2-(3,4-dimethyl-1H-pyrrolyl) propanoic acid (PP-Ala), respectively. Next, PUR-1 was isolated from a heat-treated solution containing PP-Val and allicin, and its structure was determined as (1E)-1-(1-((1S)-1-carboxy-2-methylpropyl)-3,4-dimethyl-1H-pyrrol-2-yl)-prop-1-enylene-3-(1-((1S)-1-carboxy-2-methylpropyl)-3,4-dimethyl-1H-pyrrol-2-ylidenium). The structure of PUR-1 suggested that PP molecules containing a 3,4-dimethyl pyrrole ring had been cross-linked by an allyl group of allicin to form conjugated pigments. While PUR-1 is a dipyrrole compound exhibiting a reddish-purple color, a color shift toward blue to green can be expected as the cross-linking reaction continues to form, for example, tri- or tetrapyrrole compounds.

Layered double hydroxide of Cd-Al/C for the Mineralization and De-coloration of Dyes in Solar and Visible Light Exposure

NASA Astrophysics Data System (ADS)

Khan, Shahid Ali; Khan, Sher Bahadar; Asiri, Abdullah M.

2016-11-01

Cd-Al/C layered double hydroxide (Cd-Al/C-LDH) and Cd-Sb/C nanocatalyst are reported here for the de-coloration and mineralization of organic dyes. These catalysts were largely characterized by FESEM, EDS, XRD, FTIR, XPS, PL and DRS. The diffuse reflectance data showed a band gap at 2.92 and 2.983 eV for Cd-Al/C-LDH and Cd-Sb/C respectively. The band gap suggested that both catalysts work well in visible range. The photoluminescence spectra indicated a peak at 623 nm for both the catalysts which further support the effectiveness of the respective catalyst in visible range. Both catalysts also showed good recyclability and durability till 4th cycle. Five dyes, acridine orange (AO), malachite green (MG), crystal violet (CV), congo red (CR) and methyl orange (MO) were used in this experiment. Various parameters of different light intensity such as visible, ultraviolet, sunlight and dark condition are observed for the de-coloration of these dyes. The de-coloration phenomenon was proceeded through adsorption assisted phot-degradation. The low cost, abundant nature, good recyclability and better dye removal efficiency make these catalysts suitable candidates for the de-coloration and mineralization of organic dyes.

Aggressive temperament predicts ethanol self-administration in late adolescent male and female rhesus macaques

PubMed Central

McClintick, Megan N.; Grant, Kathleen A.

2017-01-01

Rationale Anxiety and aggression are associated with ethanol self-administration, but these behaviors can serve as either risk factors for or consequences of heavy drinking in rodents and humans. Baseline levels of aggressive-like and anxious-like behavior in non-human primates have not yet been characterized in relation to future or prior ethanol intake. Objective To test the association between temperament at baseline with future ethanol self-administration in late adolescent male (n=21) and female (n=11) rhesus monkeys. Methods Shortly after entering the laboratory and before exposure to ethanol, the Human Intruder Test (HIT) and the Novel Object Test (NOT) were used to determine baseline anxious-like and aggressive-like behavior in age-matched male and female rhesus monkeys (Macaca mulatta). The monkeys were induced to drink ethanol 4% (w/v) using a schedule-induced polydipsia procedure, followed by “open-access” ethanol self-administration in which the monkeys were allowed a choice of water or 4% ethanol (w/v) for 22 hours/day (h/d) for 52 weeks. Results Aggressive monkeys self-administered more ethanol and attained higher Blood Ethanol Concentrations (BECs). No significant differences in ethanol intakes or BECs were found between anxious and non-anxious monkeys or between behaviorally inhibited and non-inhibited monkeys. Baseline aggressive behavior positively correlated with ethanol intake and intoxication. Conclusions Baseline reactive aggression was associated with higher future ethanol intake and intoxication. While significant sex differences in HIT reactivity were observed, the relationship between aggression and ethanol drinking was observed across sex and is not sex-specific. PMID:27627910

Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys.

PubMed

Huang, Luping Z; Parameswaran, Neeraja; Bordia, Tanuja; Michael McIntosh, J; Quik, Maryka

2009-05-01

Nicotine reduces dopaminergic deficits in parkinsonian animals when administered before nigrostriatal damage. Here we tested whether nicotine is also beneficial when given to rats and monkeys with pre-existing nigrostriatal damage. Rats were administered nicotine before and after a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, and the results compared with those in which rats received nicotine only after lesioning. Nicotine pre-treatment attenuated behavioral deficits and lessened lesion-induced losses of the striatal dopamine transporter, and alpha6beta2* and alpha4beta2* nicotinic receptors (nAChRs). By contrast, nicotine administered 2 weeks after lesioning, when 6-hydroxydopamine-induced neurodegenerative effects are essentially complete, did not improve these same measures. Similar results were observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Nicotine did not enhance striatal markers when administered to monkeys with pre-existing nigrostriatal damage, in contrast to previous data that showed improvements when nicotine was given to monkeys before lesioning. These combined findings in two animal models suggest that nicotine is neuroprotective rather than neurorestorative against nigrostriatal damage. Receptor studies with (125)I-alpha-conotoxinMII and the alpha-conotoxinMII analog E11A were next performed to determine whether nicotine treatment pre- or post-lesioning differentially affected expression of alpha6alpha4beta2* and alpha6(nonalpha4)beta2* nAChR subtypes in striatum. The observations suggest that protection against nigrostriatal damage may be linked to striatal alpha6alpha4beta2* nAChRs.

Dopant effects on charge transport to enhance performance of phosphorescent white organic light emitting diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Liping; Chen, Jiangshan; Ma, Dongge, E-mail: mdg1014@ciac.ac.cn

2015-11-07

We compared the performance of phosphorescent white organic light emitting diodes (WOLEDs) with red-blue-green and green-blue-red sequent emissive layers. It was found that the influence of red and green dopants on electron and hole transport in emissive layers leads to the large difference in the efficiency of fabricated WOLEDs. This improvement mechanism is well investigated by the current density-voltage characteristics of single-carrier devices based on dopant doped emissive layers and the comparison of electroluminescent and photoluminescence spectra, and attributed to the different change of charge carrier transport by the dopants. The optimized device achieves a maximum power efficiency, current efficiency,more » and external quantum efficiency of 37.0 lm/W, 38.7 cd/A, and 17.7%, respectively, which are only reduced to 32.8 lm/W, 38.5 cd/A, and 17.3% at 1000 cd/m{sup 2} luminance. The critical current density is as high as 210 mA/cm{sup 2}. It can be seen that the efficiency roll-off in phosphorescent WOLEDs can be well improved by effectively designing the structure of emissive layers.« less

Epigallocatechin-3-gallate improves cardiac hypertrophy and short-term memory deficits in a Williams-Beuren syndrome mouse model

PubMed Central

Bosch-Morató, Mònica; Guivernau, Biuse; Albericio, Guillermo; Muñoz, Francisco J.; Pérez-Jurado, Luis A.

2018-01-01

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26–28 genes at chromosome band 7q11.23. The complete deletion (CD) mouse model mimics the most common deletion found in WBS patients and recapitulates most neurologic features of the disorder along with some cardiovascular manifestations leading to significant cardiac hypertrophy with increased cardiomyocytes’ size. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has been associated with potential health benefits, both on cognition and cardiovascular phenotypes, through several mechanisms. We aimed to investigate the effects of green tea extracts on WBS-related phenotypes through a phase I clinical trial in mice. After feeding CD animals with green tea extracts dissolved in the drinking water, starting at three different time periods (prenatal, youth and adulthood), a set of behavioral tests and several anatomical, histological and molecular analyses were performed. Treatment resulted to be effective in the reduction of cardiac hypertrophy and was also able to ameliorate short-term memory deficits of CD mice. Taken together, these results suggest that EGCG might have a therapeutic and/or preventive role in the management of WBS. PMID:29554110

Monitoring of essential and heavy metals in green tea from different geographical origins.

PubMed

Brzezicha-Cirocka, Justyna; Grembecka, Małgorzata; Szefer, Piotr

2016-03-01

The present study measured the concentrations of toxic metals (Cd, Pb) and other elements (Ca, K, Mg, Na, P, Mn, Fe, Zn, Cu, Co, Cr, Ni) in tea leaves and their infusions. The total metal contents were determined by atomic absorption spectrometry. Phosphorus concentration was determined using an ultraviolet-visible spectrophotometer. Assessment of the mineral composition enabled determination of the leaching percentage and the risk of exceeding provisional tolerable weekly intake for Cd through daily tea consumption. The concentrations of bioelements were analyzed based on the recommended daily intake values for each. According to recently established standards, green tea was found to be a rich source of Mn. The average Pb and Cd levels in a 200-mL beverage were 0.002 and 0.003 mg, respectively. Indian teas had the highest percentage of Cd leaching (43.8%) and Chinese tea had the lowest (9.41%). Multivariate analysis techniques such as factor analysis and cluster analysis were used to differentiate samples according to geographical origin (China, India, or Japan). Potassium, P, Mn, Fe, Cu, Co, and Cd were effective descriptors for the identification of tea samples from China, India, and Japan.

Synthesis, spectral characterization, thermal and photoluminescence properties of Zn(II) and Cd(II)-azido/thiocyanato complexes with thiazolylazo dye and 1,2-bis(diphenylphoshino)ethane.

PubMed

Yamgar, B A; Sawant, V A; Bharate, B G; Chavan, S S

2011-01-01

A series of complexes of the type [M(L)(dppe)X2]; where M=Zn(II) or Cd(II); L=4-(2'-thiazolylazo)chlorobenzene (L1), 4-(2'-thiazolylazo)bromobenzene (L2) and 4-(2'-thiazolylazo) iodobenzene (L3); dppe=1,2-bis(diphenylphosphino)ethane; X=N3- or NCS- have been prepared and characterized on the basis of their microanalysis, molar conductance, thermal, IR, UV-vis and 1H NMR spectral studies. IR spectra show that the ligand L is coordinated to the metal atom in bidentate manner via azo nitrogen and thiazole nitrogen. An octahedral structure is proposed for all the complexes. The thermal behavior of the complexes revealed that the thiocyanato complexes are thermally more stable than the azido complexes. All the complexes exhibit blue-green emission with high quantum yield as the result of the fluorescence from the intraligand emission excited state. Copyright © 2010 Elsevier B.V. All rights reserved.

[Indocyanine green infrared fluorescence angiography and vascular cast--preparation in experimental choroidal circulatory disturbance].

PubMed

Matsunaga, H; Andoh, A; Matsubara, T; Fukushima, I; Takahashi, K; Ohkuma, H; Uyama, M

1996-03-01

We performed experiments in 20 monkey eyes in order to clarify basic problems about interpretation of indocyanine green fluorescence angiography (ICG angiography). We severed the temporal group of posterior ciliary arteries to produce choroidal circulatory disturbance. ICG angiography was performed immediately, and 2 days, 4 days, and 2 weeks later. Following each ICG angiography, the eye was studied by plastic vascular cast technique with scanning electron microscopy. Immediately after occlusion, ICG angiography showed filling defect in the temporal choroidal hemisphere during the early phase. In the later phase, this area was gradually filled by the dye from choroidal arteries in the nasal hemisphere and the anterior ciliary arteries. Vascular cast preparations showed filling defect in the temporal choroidal hemisphere, corresponding with the early ICG angiogaphic findings. Both filling delay in ICG angiography and filling defect in vascular casts improved daily after occlusion. Two weeks after occlusion, The area of choroidal infarct temporal to the macula turned into chorioretinal atrophy. This area showed hypofluorescence in the early-phase ICG angiography and filling defect of the choriocapillaris in plastic casts. The early-phase ICG angiographic findings thus corresponded well with observations of vascular casts. We conclude that ICG angiography correctly reflects the actual circulatory disturbances in the choroid.

In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys.

PubMed

Reddy, V B G; Doss, G A; Karanam, B V; Samuel, K; Lanza, T J; Lin, L S; Yu, N X; Zhang, A S; Raab, C E; Stearns, R A; Kumar, S

2010-09-01

The metabolism and excretion of taranabant (MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2{[5-(trifluoromethyl)pyridine-2-yl]oxy}propanamide), a potent cannabinoid-1 receptor inverse agonist, were evaluated in rats and rhesus monkeys. Following administration of [¹⁴C]taranabant, the majority of the radioactivity was excreted within 72 h. In both rats and rhesus monkeys, taranabant was eliminated primarily via oxidative metabolism, followed by excretion of metabolites into bile. Major pathways of metabolism that were common to rats and rhesus monkeys included hydroxylation at the benzylic carbon adjacent to the cyanophenyl ring to form a biologically active circulating metabolite M1, and oxidation of one of the two geminal methyl groups of taranabant or M1 to the corresponding diastereomeric carboxylic acids. Oxidation of the cyanophenyl ring, followed by conjugation with glutathione or glucuronic acid, was a major pathway of metabolism only in the rat and was not detected in the rhesus monkey. Metabolism profiles of taranabant in liver microsomes in vitro were qualitatively similar in rats, rhesus monkeys and humans and included formation of M1 and oxidation of taranabant or M1 to the corresponding carboxylic acids via oxidation of a geminal methyl group. In human liver microsomes, metabolism of taranabant was mediated primarily by CYP3A4.

New oligomers containing pendant 4-aryl-7-phenylfluorene units as efficient charge transporting materials for OLEDs

NASA Astrophysics Data System (ADS)

Krucaite, G.; Baranauskyte, U.; Tavgeniene, D.; Andruleviciute, V.; Sutkuviene, S.; Yao, B.; Xie, Z.; Zhang, B.; Grigalevicius, S.

2017-10-01

Monomers and oligomers containing electronically isolated 4-aryl-7-phenylfluorene fragments have been synthesized by the multi-step synthetic route. The materials were characterized by thermo-gravimetric analysis, differential scanning calorimetry and electron photoemission technique. The oligomers represent materials of very high thermal stability having initial thermal degradation temperatures in the range of 402-412 °C. The glass transition temperatures of the amorphous oligomers were in the rage of 97-129 °C. The electron photoemission spectra of thin layers of the oligomeric materials showed ionization potentials in the range of 5.7-6.1 eV. Hole injecting/transporting properties of the electroactive oligomers were tested in the structures of organic light emitting diodes with tris(quinolin-8-olato)aluminium as a green emitter. The device containing hole-transporting material with 4-biphenyl-7-phenylfluorene electrophores exhibited the best overall performance with low turn on voltage of 4.4 V, high current efficiency exceeding 3.6 cd/A and maximum brightness exceeding 3200 cd/m2.

Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis.

PubMed

Sugawara, I; Sun, L; Mizuno, S; Taniyama, T

2009-01-01

We have reported previously that recombinant BCG Tokyo (Ag85A) (rBCG-Ag85A[Tokyo]) shows promise as a tuberculosis vaccine, demonstrating protective efficacy in cynomolgus monkeys. As a next step, rhesus monkeys were utilized because they are also susceptible to Mycobacterium tuberculosis and show a continuous course of infection resembling human tuberculosis. The recombinant BCG vaccine (5x10(5) CFU per monkey) was administered once intradermally into the back skin to three groups of rhesus monkeys, and its protective efficacy was compared for 4months with that of its parental BCG Tokyo strain. Eight week vaccination of the monkeys with rBCG-Ag85A[Tokyo] resulted in a reduction of tubercle bacilli CFU (p<0.01) and lung pathology in animals infected intratracheally with 3000 CFU H37Rv M. tuberculosis. Vaccination prevented an increase in the old tuberculin test after challenge with M. tuberculosis and reaction of M. tuberculosis-derived antigen. Thus, it was shown that even in rhesus monkeys rBCG-Ag85A[Tokyo] induced higher protective efficacy than BCG Tokyo.

Protein phosphorylations in poliovirus infected cells.

PubMed

James, L A; Tershak, D R

1981-01-01

In vivo phosphorylation of proteins that are associated with polysomes of poliovirus-infected VERO (African green monkey kidney) and HeLa (Henrietta Lacks) cells differed from phosphorylations observed with uninfected cells that were fed fresh medium. With both types of cells infection stimulated phosphorylation of proteins with molecular weights of 40 000-41 000, 39 000, 34 000, 32 000, and 24 000. Similarities of phosphorylations in VERO and HeLa cells suggest that they are a specific consequence of infection and might serve a regulatory function during protein synthesis.

Characterization of the Fusion and Attachment Glycoproteins of Human Metapneumovirus and Human Serosurvey to Determine Reinfection Rates

DTIC Science & Technology

2007-06-27

Reinfection Rates" Name of Candidate: Julie Pavlin Doctor of Philosophy Degree 27 June 2007 Date Dissertation and Abstract Approved: (~ k( r (~~ t ~z-7...m s t e r R a b b it Rhesus macaque Cynomolgus macaque African green monkey Chimpanzee 75 Immunizations with sF and sG. Previous studies have...301�񔪔 J ge anco, Ph.D. V’ ion Systems, I c. ~~e~ David ReIman , M.D. Stanford University Committee Member (,/1.7 )07

Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide) Copolymer for Tumor Targeting

PubMed Central

Son, Gyung Mo; Kim, Hyun Yul; Ryu, Je Ho; Chu, Chong Woo; Kang, Dae Hwan; Park, Su Bum; Jeong, Young-IL

2014-01-01

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting. PMID:25216338

Performing monkeys of Bangladesh: characterizing their source and genetic variation.

PubMed

Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Akhtar, Sharmin; Kanthaswamy, Sree; Smith, David Glenn

2016-04-01

The acquisition and training of monkeys to perform is a centuries-old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations, and may escape from their owners or may be released into other populations. In order to determine whether this tradition involving the acquisition and movement of animals has influenced the population structure of free-ranging rhesus macaques in Bangladesh, we first characterized the source of these monkeys. Biological samples from 65 performing macaques collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16 %) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89 %) were transitions, and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise differences for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. The collection of performing monkeys from India was also evident.

Performing monkeys of Bangladesh: characterizing their source and genetic variation

PubMed Central

Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Akhtar, Sharmin; Kanthaswamy, Sree; Smith, David Glenn

2016-01-01

The acquisition and training of monkeys to perform is a century's old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations and may escape from their owners or be released into other populations. In order to determine whether this tradition, that involves the acquisition and movement of animals, has influenced the population structure of free-ranging rhesus macaques in Bangladesh we first characterized the source of these monkeys. Biological samples from 65 performing macaques, collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16%) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89%) were transitions and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise difference for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. Collection of performing monkeys from India was also evident. PMID:26758818

Species difference in the mechanism of nonlinear pharmacokinetics of E2074, a novel sodium channel inhibitor, in rats, dogs, and monkeys.

PubMed

Nagaya, Yoko; Takenaka, Osamu; Kusano, Kazutomi; Yoshimura, Tsutomu

2013-05-01

New chemical entities often exhibit nonlinear pharmacokinetics (PK) profiles in experimental animals. However, the number of studies that have focused on species differences in nonlinear PK is very limited; thus, the aim of this study was to clarify the mechanism of the nonlinear PK of E2074 (2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl)oxy]-8-azabicyclo[3.2.1]oct-8-yl}propyl]-4,5-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-one), a novel sodium channel inhibitor, in rats, dogs, and monkeys. Nonlinear PK profiles with more than dose-proportional increases of Cmax and area under the plasma concentration curve were observed in all species after oral administration. The Michaelis-Menten constant (Km) values of hepatic microsomal metabolism were 7.23 and 0.41 μM in rats and dogs in vitro, respectively, which were lower than the unbound maximum plasma concentrations after oral administration in vivo, indicating that the nonlinear PK in rats and dogs was attributable to the saturation of hepatic metabolism. However, we do not believe that the saturation of hepatic metabolism was the mechanism of nonlinearity in monkeys because of the high Km value (42.44 μM) observed in liver microsomes. Intestinal metabolism was observed in monkey intestinal microsomes but not in rats and dogs, and the nonlinear PK in monkeys was diminished by inhibition of intestinal metabolism with a concomitant oral dose of ketoconazole. These results suggest that saturation of the intestinal metabolism is the potential mechanism of nonlinearity in monkeys. P-glycoprotein was not involved in the nonlinear PK profiles in any species. In conclusion, the mechanism of the nonlinear PK of E2074 is species dependent, with the saturation of hepatic metabolism in rats and dogs and that of intestinal metabolism in monkeys being the primary cause.

Evaluation of Serum Lipid, Thyroid, and Hepatic Clinical Chemistries in Association With Serum Perfluorooctanesulfonate (PFOS) in Cynomolgus Monkeys After Oral Dosing With Potassium PFOS

PubMed Central

Allen, Bruce C.; Andres, Kara L.; Ehresman, David J.; Falvo, Ria; Provencher, Anne; Olsen, Geary W.; Butenhoff, John L.

2017-01-01

Abstract An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4–6/sex) received 3 separate K+ PFOS doses (11–17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 μg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 μg/ml for male and female monkeys, respectively. Compared to the 2013–2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 μg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of exposure. PMID:28115654

Distinct mobilization of leukocytes and hematopoietic stem cells by CXCR4 peptide antagonist LY2510924 and monoclonal antibody LY2624587

PubMed Central

Peng, Sheng-Bin; Van Horn, Robert D.; Yin, Tinggui; Brown, Robin M.; Roell, William C.; Obungu, Victor H.; Ruegg, Charles; Wroblewski, Victor J.; Raddad, Eyas; Stille, John R.

2017-01-01

Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play a critical role in mobilization and redistribution of immune cells and hematopoietic stem cells (HSCs). We evaluated effects of two CXCR4-targeting agents, peptide antagonist LY2510924 and monoclonal antibody LY2624587, on mobilizing HSCs and white blood cells (WBCs) in humans, monkeys, and mice. Biochemical analysis showed LY2510924 peptide blocked SDF-1/CXCR4 binding in all three species; LY2624587 antibody blocked binding in human and monkey, with minimal activity in mouse. Cellular analysis showed LY2624587 antibody, but not LY2510924 peptide, down-regulated cell surface CXCR4 and induced hematological tumor cell death; both agents have been shown to inhibit SDF-1/CXCR4 interaction and downstream signaling. In animal models, LY2510924 peptide induced robust, prolonged, dose- and time-dependent WBC and HSC increases in mice and monkeys, whereas LY2624587 antibody induced only moderate, transient increases in monkeys. In clinical trials, similar pharmacodynamic effects were observed in patients with advanced cancer: LY2510924 peptide induced sustained WBC and HSC increases, while LY2624587 antibody induced only minimal, transient WBC changes. These distinct pharmacodynamic effects in two different classes of CXCR4 inhibitors are clinically important and should be carefully considered when designing combination studies with immune checkpoint inhibitors or other agents for cancer therapy. PMID:29212254

Composition-Tunable Optical Properties of Zn x Cd(1 - x)S Quantum Dot-Carboxymethylcellulose Conjugates: Towards One-Pot Green Synthesis of Multifunctional Nanoplatforms for Biomedical and Environmental Applications

NASA Astrophysics Data System (ADS)

Mansur, Alexandra A. P.; Mansur, Herman S.; Caires, Anderson J.; Mansur, Rafael L.; Oliveira, Luiz C.

2017-07-01

Quantum dots (QDs) are colloidal semiconductor nanocrystals with unique properties that can be engineered by controlling the nanoparticle size and chemical composition by doping and alloying strategies. However, due to their potential toxicity, augmenting their biocompatibility is yet a challenge for expanding to several biomedical and environmentally friendly applications. Thus, the main goal of this study was to develop composition-tunable and biocompatible Zn x Cd1 - x S QDs using carboxymethylcellulose polysaccharide as direct capping ligand via green colloidal aqueous route at neutral pH and at room temperature for potential biomedical and environmental applications. The ternary alloyed QDs were extensively characterized using UV-vis spectroscopy, photoluminescence spectroscopy (PL), transmission electron microscopy (TEM), X-ray diffraction (XRD), electron energy loss spectroscopy (EELS), and X-ray photoelectrons spectroscopy (XPS). The results indicated that Zn x Cd(1 - x)S QDs were surface stabilized by carboxymethylcellulose biopolymer with spherical morphology for all composition of alloys and narrow sizes distributions ranging from 4 to 5 nm. The XRD results indicated that monophasic ternary alloyed Zn x Cd1 - x S nanocrystals were produced with homogenous composition of the core as evidenced by EELS and XPS analyses. In addition, the absorption and emission optical properties of Zn x Cd1 - x S QDs were red shifted with increasing the amount of Cd2+ in the alloyed nanocrystals, which have also increased the quantum yield compared to pure CdS and ZnS nanoparticles. These properties of alloyed nanomaterials were interpreted based on empirical model of Vegard's law and chemical bond model (CBM). As a proof of concept, these alloyed-QD conjugates were tested for biomedical and environmental applications. The results demonstrated that they were non-toxic and effective fluorophores for bioimaging live HEK293T cells (human embryonic kidney cells) using confocal laser scanning fluorescence microscopy. Moreover, these conjugates presented photocatalytic activity for photodegradation of methylene blue used as model organic industrial pollutant in water. Hence, composition-tunable optical properties of ternary Zn x Cd1 - x S ( x = 0-1) fluorescent alloyed QDs was achieved using a facile eco-friendly aqueous processing route, which can offer promising alternatives for developing innovative nanomaterials for applications in nanomedicine and environmental science and technology.

Hematologic and lymphocyte immunophenotypic reference values for normal rhesus monkey (Macaca mulatta) umbilical cord blood; gravidity may play a role in study design.

PubMed

Rogers, Linda B; Kaack, M Bernice; Henson, Michael C; Rasmussen, Terri; Henson, Elizabeth; Veazey, Ronald S; Krogstad, Donald J; Davison, Billie B

2005-06-01

Hematology and flow cytometry reference values for rhesus umbilical cord blood (UCB) were established in 17 healthy infant rhesus monkeys delivered by elective cesarean section 10 days preterm. The infants were born to age matched, singly caged primigravid or secundigravid dams. The hematology and flow cytometry values were determined by automated cell counter and by FACS. No significant differences were observed with respect to infant gender. With respect to gravida, the primigravid infants had a significantly higher percentage (P= 0.05) of CD20(+) B lymphocytes in UCB. These results provide useful reference values for future studies of maternal - fetal disease transmission, vaccine and drug evaluation in non-human primate pregnancy, as well as fetal programming and immune modulation, gene therapy and the use of UCB as a source of stem cells for research and transplantation. Importantly, our results suggest that maternal gravidity may be an important variable to consider.

Placental Transport of Zidovudine in the Rhesus Monkey

PubMed Central

King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

1993-01-01

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection. Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment. PMID:18475334

Pathogenic properties of enterohepatic Helicobacter spp. isolated from rhesus macaques with intestinal adenocarcinoma

PubMed Central

Lertpiriyapong, Kvin; Handt, Laurence; Feng, Yan; Mitchell, Thomas W.; Lodge, Kenneth E.; Shen, Zeli; Dewhirst, Floyd E.; Muthupalani, Sureshkumar

2014-01-01

Considerable progress has been made in understanding the roles of Helicobacter pylori in inflammation and gastric cancer; however, far less is known about the roles of enterohepatic Helicobacter species (EHS) in carcinogenesis and their zoonotic or pathogenic potential. We determined the prevalence of EHS infection in a cohort of geriatric rhesus monkeys in which intestinal adenocarcinoma (IAC) is common and investigated the association between EHS infection and IAC. The cohort consisted of 36 animals, 14 of which (age 26–35 years) had IAC. Of the 36 rhesus, 35 (97 %) were positive for EHS using PCR or bacterial isolation from faeces, colonic or tumour tissues. Only a single rhesus, which had IAC, was negative for EHS by all detection methods. The EHS identified by 16S rRNA sequencing in this study were from three Helicobacter taxa: Helicobacter macacae (previously rhesus monkey taxon 1), Helicobacter sp. rhesus monkey taxon 2, previously described from strain MIT 99-5507, and Helicobacter sp. rhesus monkey taxon 4, related to Helicobacter fennelliae. Thirteen of 14 monkeys with IAC were positive for either H. macacae (7/13, 54 %), EHS rhesus monkey taxon 4 (4/13, 31 %) or a mixture of the two EHS (2/13, 15 %). These results indicate that EHS are prevalent among aged rhesus macaques with IAC. Using Helicobacter genus-specific florescent in situ hybridization, EHS were detected on the surface of colonic epithelia of infected monkeys. All Helicobacter isolates, including H. macacae, effectively adhered to, invaded, and significantly induced proinflammatory genes, including IL-8, IL-6, TNF-α and iNOS, while downregulating genes involved in the function of inflammasomes, particularly IL-1β, CASPASE-1, NRLP3, NLRP6 and NLRC4 in the human colonic T84 cell line (P<0.0001). These results suggest that EHS may represent an aetiological agent mediating diarrhoea, chronic inflammation, and possibly intestinal cancer in non-human primates, and may play a role in similar disease syndromes in humans. Downregulation of inflammasome function may represent an EHS strategy for long-term persistence in the host and play a role in inducing pathological changes in the host’s lower bowel. PMID:24696515

Organic light-emitting diodes with direct contact-printed red, green, blue, and white light-emitting layers

NASA Astrophysics Data System (ADS)

Chen, Sun-Zen; Peng, Shiang-Hau; Ting, Tzu-Yu; Wu, Po-Shien; Lin, Chun-Hao; Chang, Chin-Yeh; Shyue, Jing-Jong; Jou, Jwo-Huei

2012-10-01

We demonstrate the feasibility of using direct contact-printing in the fabrication of monochromatic and polychromatic organic light-emitting diodes (OLEDs). Bright devices with red, green, blue, and white contact-printed light-emitting layers with a respective maximum luminance of 29 000, 29 000, 4000, and 18 000 cd/m2 were obtained with sound film integrity by blending a polymeric host into a molecular host. For the red OLED as example, the maximum luminance was decreased from 29 000 to 5000 cd/m2 as only the polymeric host was used, or decreased to 7000 cd/m2 as only the molecular host was used. The markedly improved device performance achieved in the devices with blended hosts may be attributed to the employed polymeric host that contributed a good film-forming character, and the molecular host that contributed a good electroluminescence character.

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM.

PubMed

Yamasaki, Tomoteru; Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Yoshida, Yuichiro; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong

2012-04-01

In this study, we evaluate the utility of 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [(18)F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V(T)) was detected in the cerebellum (V(T) = 11.5). [(18)F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [(18)F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

RepSox improves viability and regulates gene expression in rhesus monkey-pig interspecies cloned embryos.

PubMed

Zhu, Hai-Ying; Jin, Long; Guo, Qing; Luo, Zhao-Bo; Li, Xiao-Chen; Zhang, Yu-Chen; Xing, Xiao-Xu; Xuan, Mei-Fu; Zhang, Guang-Lei; Luo, Qi-Rong; Wang, Jun-Xia; Cui, Cheng-Du; Li, Wen-Xue; Cui, Zheng-Yun; Yin, Xi-Jun; Kang, Jin-Dan

2017-05-01

To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey-pig interspecies somatic cell nuclear transfer (iSCNT) embryos. Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p < 0.05), but not of Sox2 compared with untreated embryos at the 2-4-cell stage. Expression of the anti-apoptotic gene, Bcl2, and the pro-apoptotic gene Bax was also affected at the 2-4-cell stage. RepSox treatment also increased the immunostaining intensity of Oct4 at the blastocyst stage (p < 0.05). Although the blastocyst developmental rate was higher in the group treated with 25 µM RepSox for 24 h than in the untreated control group (2.4 vs. 1.2%, p > 0.05), this was not significant. RepSox can improve the developmental potential of rhesus monkey-pig iSCNT embryos by regulating the expression of pluripotency-related genes.

Antigenotoxic and Apoptotic Activity of Green Tea Polyphenol Extracts on Hexavalent Chromium-Induced DNA Damage in Peripheral Blood of CD-1 Mice: Analysis with Differential Acridine Orange/Ethidium Bromide Staining

PubMed Central

García-Rodríguez, María del Carmen; Carvente-Juárez, Megumi Monserrat; Altamirano-Lozano, Mario Agustín

2013-01-01

This study was conducted to investigate the modulating effects of green tea polyphenols on genotoxic damage and apoptotic activity induced by hexavalent chromium [Cr (VI)] in CD-1 mice. Animals were divided into the following groups: (i) injected with vehicle; (ii) treated with green tea polyphenols (30 mg/kg) via gavage; (iii) injected with CrO3 (20 mg/kg) intraperitoneally; (iv) treated with green tea polyphenols in addition to CrO3. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCEs) obtained from peripheral blood at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. Treatment of green tea polyphenols led to no significant changes in the MN-PCEs. However, CrO3 treatment significantly increased MN-PCEs at 24 and 48 h after injection. Green tea polyphenols treatment prior to CrO3 injection led to a decrease in MN-PCEs compared to the group treated with CrO3 only. The average of apoptotic cells was increased at 48 h after treatment compared to control mice, suggesting that apoptosis could contribute to eliminate the DNA damaged cells induced by Cr (VI). Our findings support the proposed protective effects of green tea polyphenols against the genotoxic damage induced by Cr (VI). PMID:24363823

Modification of Lethality Induced by Staphylococcal Enterotoxin B in Dutch Rabbits

DTIC Science & Technology

1980-03-01

Purification of staphylococcal enterotoxin 2. Liu CT, DeLauter RD. Faulkner RT: cation of monkeys by intravenous staphylo- B. Biochemistry 4:1011...nteotoinB (EB)ata ds- to produce death within 24 hours in Staphylococcal enterotoxin B is a age level of 50 pg/kg of body weight monkeys , 13 dogs...8KB accumulates in the renal proximal peatbyrod&-tomy and Mesm R. D. DeaII15 and caq1 G. 0Croe for tehela sitace. the monkey and rabbit is still of much

The Kinetics and Dynamics of Elementary Gas-Phase Reactions

DTIC Science & Technology

2002-09-01

We report CRDS measurements of thin films of oxazine 1, oxazine 170 and malachite green dyes deposited on borosilicate substrates. The method...measure monolayer and sub-monolayer quantities of dye. The minimum observed concentration of malachite green in the present work was calculated to be...the dyes: at surface coverages of ~ 2.8 × 10-7 mol m-2, the ratio of malachite green dimers to monomers was estimated as Cd/Cm = 0.22. The Kinetics

Pediatric hepatic hemangiosarcoma in a rhesus macaque (Macaca mulatta)

PubMed Central

Mejía, A.F.; Gierbolini, L.; Jacob, B.; Westmoreland, S.V.

2009-01-01

Background Pediatric hepatic angiosarcoma is a rare condition in children with poor prognosis. Microscopically this neoplasm has a particular ‘Kaposi-form’ arrangement. Hemangiosarcoma in non-human primates is a rare finding. Methods Gross and microscopic examination of a 3-year-old rhesus were performed. Immunohistochemistry was used to characterize the hepatic hemangiosarcoma. Results The gross necropsy revealed hemoabdomen and a 4 × 3 × 3 cm mass in the liver with multiple smaller masses throughout the hepatic parenchyma. Histopathology confirmed a poorly differentiated hemangiosarcoma. Other organs submitted were free of metastases. Conclusions Hemangiosarcoma in non-human primates has been rarely reported. Diagnosis was confirmed by expression of endothelial-specific markers CD31 and vWF by immunohistochemistry. Due to the young age of this monkey and the particular solid pattern throughout the mass this neoplasm resembles pediatric hepatic angiosarcoma in humans. PMID:18671765

Results from the EPL monkey-pod experiment conducted as part of the 1974 NASA/Ames shuttle CVT-2

NASA Technical Reports Server (NTRS)

Rahlmann, D. F.; Kodama, A. M.; Mains, R. C.; Pace, N.

1974-01-01

The participation of the Environmental Physiology Laboratory (EPL) in the general purpose laboratory concept verification test 3 is documented. The EPL Monkey-Pod Experiment was designed to incorporate a 10-12 kg, pig tailed monkey, Macaca nemestrina, into the pod and measure the physiological responses of the animal continuously. Four major elements comprise the EPL Monkey-Pod Experiment System: (1) a fiberglass pod containing the instrumented monkey plus feeder and watering devices, (2) an inner console containing the SKYLAB mass spectrometer with its associated valving and electronic controls, sensing, control and monitoring units for lower body negative pressure, feeder activity, waterer activity, temperatures, and gas metabolism calibration, (3) an umbilical complex comprising gas flow lines and electrical cabling between the inner and outer console and (4) an outer console in principle representing the experiment support to be provided from general spacecraft sources.

Preclinical toxicologic evaluation of 5-isoxazoleacetic acid, alpha-amino-3-chloro-4,5-dihydro-(nsc 163501), in dogs, monkeys, and cdf1 mice. Final report 24 Apr-13 Sep 78

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denine, E.P.; Stout, L.D.; Peckham, J.C.

1978-11-10

Dose-limiting gastrointestinal toxicosis was qualitatively similar in dogs, monkeys, and mice. In dogs and monkeys, anorexia and/or oligodipsia were cardinal signs. Severity of intoxication was indicated by progression to a diarrheal syndrome. Intoxication of the erythron was indicated in the dog and monkey studies. Quantitatively, mice were the most resistant to toxicity, and monkeys were more resistant than dogs. In dogs, fractionation of a single dose to five daily doses resulted in marked cumulative toxicity. Further fractionation to 10 daily doses produced only additive intoxication. Fractionation of a single dose to weekly doses offered some protection from additive toxicity. Similarmore » results were obtained when 5 daily doses were fractionated to three 5-day courses of treatment separated by 9-day rest periods.« less

Results from the EPL monkey-pod flight experiments conducted aboard the NASA/Ames CV-990, May 1976

NASA Technical Reports Server (NTRS)

Rahlmann, D. F.; Kodama, A. M.; Mains, R. C.; Pace, N.

1976-01-01

The participation of the Environmental Physiology Laboratory (EPL) in the general purpose laboratory concept verification test 3 is documented. The EPL Monkey-Pod Experiment was designed to incorporate a 10-12 kg, pig tailed monkey, Macaca nemestrina, into the pod and measure the physiological responses of the animal continously. Four major elements comprise the EPL Monkey-Pod Experiment System: (1) a fiberglass pod containing the instrumented monkey plus feeder and watering devices, (2) an inner console containing the SKYLAB mass spectrometer with its associated valving and electronic controls, sensing, control and monitoring units for lower body negative pressure, feeder activity, waterer activity, temperatures, and gas metabolism calibration, (3) an umbilical complex comprising gas flow lines and electrical cabling between the inner and outer console and (4) an outer console in principle representing the experiment support to be provided from general space craft sources.

Flexible AMOLED backplane using pentacene TFT

NASA Astrophysics Data System (ADS)

Song, Chung Kun; Ryu, Gi Seong

2005-01-01

In this paper we fabricated a panel consisting of an array of organic TFTs (OTFT) and organic LEDs (OLED) in order to demonstrate the possible application of OTFTs to flexible active matrix OLED (AMOLED). The panel was composed of 64×64 pixels on 4 inch size PET substrate in which each pixel had one OTFT integrated with one green OLED. The panel successfully demonstrated to display some letters and pictures by emitting green light with luminance of 20 cd/m2 at 6 V, which was controlled by the gate voltage of OTFT. In addition we also developed fabrication processes for pentacene TFT with PVP gate on PET substrate. The OTFTs produced the maximum mobility of 1.2 cm2/V"sec and on/off current ratio of 2×106.

Evaluation of Pepsinogen I as a Biomarker of Drug-induced Gastric Mucosal Injury in Cynomolgus Monkeys.

PubMed

Ennulat, Daniela; Lynch, Karen M; Kimbrough, Carie L; Mirabile, Rosanna C; Rehm, Sabine

2017-02-01

Gastric mucosal injury is frequently observed in nonclinical studies of nonhuman primates. Because microscopic evaluation of stomach is generally a terminal procedure, our objective was to determine whether serum pepsinogen I (PG I) could serve as a noninvasive biomarker for detection of gastric mucosal injury in monkey. Serum PG I was measured using a commercial human immunoassay in cynomolgus monkeys ( n = 166) prior to dosing and/or terminally in 11 studies of up to 1 month duration. Mean ( SD) PG I values (ug/L) for monkeys with ( n = 59) and without ( n = 100) gastric mucosal degeneration were 101 (215) and 28 (12.6), respectively. For monkeys with baseline and terminal PG I data, mean ( SD) fold change (ratio of terminal to baseline PG I) for monkeys with ( n = 57) and without ( n = 76) glandular degeneration were 4.1 (11.3) and 1 (0.28). Receiver operating characteristic area under the curve (AUC) data demonstrated moderate diagnostic accuracy for serum PG I for glandular degeneration, AUC ( SE) 0.789 (0.04), with improved diagnostic accuracy as a fold change of baseline, AUC ( SE) 0.816 (0.04), consistent with the large interindividual but low intraindividual variability of serum PG I values in control monkeys. These data demonstrate that serum PG I is a useful biomarker of drug-induced gastric mucosal injury in the cynomolgus monkey.

Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

PubMed Central

Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

2011-01-01

Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

Monitoring Cellular Interactions during T Cell Activation at the Single Molecule Level Using Semiconductor Quantum-Dots

DTIC Science & Technology

2005-05-10

avidin-fusion constructs in mammalian immune cells. To facilitate detection, an epitope tag (HA, derived from the influenza A virus haemagglutinin...Enhanced Green Fluorescent protein (EGFP) cassette. The IRES element (internal ribosome entry site of the encephalomyocarditis virus ) permits both the...AVIDIN CD4 4 AVIDIN tAT .RES’ EGFP TRES’ EGFP IRES’ EGFp 1RES. EGFP g9K LP tar LP gK LP ITTK LIP IE "M33 Ee TM NAMI IAV ~ 𔃺M A ,A,0,, MIMI, A161 TM

Toxicity in Rhesus Monkeys Following Administration of the 8-Aminoquinoline 8-[(4-amino-l-methylbutyl)amino]-5(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511)

DTIC Science & Technology

2008-09-01

been synthesized) [17,18]. The rhesus monkey has also shown consistent MHb elevation follow- ing exposure to benzocaine as well as the 8...anesthetic-induced methemoglobinemia and sulfhemo- globinemia in macaques: a comparison of benzocaine and lido- caine. J Appl Toxicol 1995;15:153–158. 20

Evaluation in Rhesus Monkeys of a Bivalent Live Attenuated Dengue Vaccine Containing Types 2 and 4 Viruses.

DTIC Science & Technology

1984-06-01

previous reports,(1) antibody levels of most of the vaccinated animals declined markedly on or before post vacination day 150. PR13s showed that the EM-4...V.H., Gould, D.J., Chapple, F.E., and Russell, P.K.: Dengue 2 vacine , viremia and Inmune response in rhesus monkeys. Infect. Immun. 27, 181-186, 1980. 2

Increased production of 11beta-hydroxysteroid dehydrogenase type 2 in the kidney microsomes of squirrel monkeys (Saimiri spp.).

PubMed

Sadosky, Patti W; Scammell, Jonathan G

2008-04-01

In squirrel monkeys (Saimiri spp.), cortisol circulates at levels much higher than those seen in man and other Old World primates, but squirrel monkeys exhibit no physiologic signs of the mineralocorticoid effects of cortisol. These observations suggest that squirrel monkeys have mechanisms for protection of the mineralocorticoid receptor (MR) from these high levels of cortisol. We previously showed that the serum cortisol to cortisone ratio in these animals is low relative to that in human serum, suggesting that production of the MR protective enzyme, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), is increased in squirrel monkeys. Here, we directly evaluate whether increased production of 11beta-HSD2, which inactivates cortisol to cortisone, is a mechanism for protection of MR. In vitro assays showed that 11beta-HSD2 activity in squirrel monkey kidney microsomes was 3 to 7 times higher than that seen in kidney microsomes from pig or rabbit. 11beta-HSD2 protein detected by Western blot analysis was 4 to 9 times greater in squirrel monkey microsomes than in pig or rabbit microsomes. Comparison of the effect of expression of either human or squirrel monkey 11beta-HSD2 on MR transactivation activity showed similar inhibition of MR response to cortisol by both enzymes, indicating that the intrinsic activities of the human and squirrel monkey enzymes are similar. These findings suggest that one mechanism by which squirrel monkeys protect the MR from activation by high cortisol levels in the kidney is by upregulation of 11beta-HSD2 activity through increased production of the enzyme.

Nutritional benefits of Crematogaster mimosae ants and Acacia drepanolobium gum for patas monkeys and vervets in Laikipia, Kenya.

PubMed

Isbell, Lynne A; Rothman, Jessica M; Young, Peter J; Rudolph, Kathleen

2013-02-01

Patas monkeys (Erythrocebus patas) are midsized primates that feed extensively on the gum of Acacia drepanolobium and the ants are housed in swollen thorns of this Acacia. Their diet resembles that expected more of smaller bodied primates. Patas monkeys are also more like smaller bodied primates in reproducing at high rates. We sought to better understand the convergence of patas monkeys with smaller bodied primates by comparing their feeding behavior on ants and gum with that of closely related, sympatric vervets (Chlorocebus pygerythrus), and analyzing the nutrient content of the gum of A. drepanolobium and of Crematogaster mimosae, the most common ant species eaten by patas monkeys in Laikipia, Kenya. All occurrences of feeding and moving during focal animal sampling revealed that 1) patas monkeys seek A. drepanolobium gum but vervets avoid it; 2) both species open swollen thorns most often in the morning when antsare less active; 3) patas monkeys continually feed onswollen thorns and gum while moving quickly throughout the day, whereas vervets reduce their consumption of these items and their travel rate at mid-day, and; 4) vervets eat young swollen thorns at a higher rate than patas monkeys. Patas monkeys are able to spend little time acquiring substantial amounts of energy, protein, and minerals from A. drepanolobium gum and C. mimosae ants each day. These findings, when coupled with evidence of causes of infant and adult female mortality, suggest that reproductive success of female patas monkeys is more immediately affected by illness, disease, interactions between adults and infants, and access to water than by food. Copyright © 2012 Wiley Periodicals, Inc.

Temperature measurement based on photoluminescence of Er3+ doped Sr0.3Cd0.7F2 microcrystal coupled to scanning thermal microscopy

NASA Astrophysics Data System (ADS)

Trannoy, N.; Sayoud, A.; Diaf, M.; Duvaut, Th.; Jouart, J. P.; Grossel, Ph.

2015-04-01

Rare earth doped sub-micrometric luminescent materials are promising candidates for temperature sensing and play an efficient role in many technological fields. In this paper, a new optical sensor is developed for measuring local temperatures. This sensor is based on a thermal-resistive probe and on photoluminescence of a luminescent fluoride microcrystal. The final purpose is to develop a device calibrated in temperature and capable of acquiring images of local temperature at sub-micrometric scale. Indeed, the sensor temperature can be obtained in two distinct ways: one from the thermal probe parameters and the other from the green photoluminescence generated in the anti-Stokes mode by the active Er ions directly excited by a red laser. The thermal probe is based on Wollaston wire whose thermal-resistive element is in platinum/rhodium. Its temperature is estimated from the probe electrical characteristics and a modeling. A microcrystal of Sr0.3Cd0.7F2: Er3+(4%)-Yb3+(6%) of about 25 μm in diameter is glued at the probe extremity. This luminescent material has the particularity to give a green emission spectrum with intensities sensitive to small temperature variations. Using the fluorescence intensity ratio (FIR) technique, the crystal temperature is estimated from the intensity measurements at green wavelengths 522, 540 and 549 nm by taking advantage of particular optical properties due to the crystalline nature of Sr0.3Cd0.7F2: Er3+-Yb3+. The microcrystal temperature is then assessed as a function of electric current in the thermal probe by applying the Boltzmann's equations. The coupling of the scanning thermal microscope (SThM) with the photoluminescence probe reveals that the particle fluorescence signal is affected by the temperature rise of an electrical microsystem submitted to a Joule heating. The first results are presented and discussed.

Highly efficient green up-conversion luminescence of Nd3+-Yb3+-Ho3+ codoped fluorite-type nanocrystals in transparent glass ceramics

NASA Astrophysics Data System (ADS)

Qiu, Jianbei; Kawamoto, Yoji; Zhang, Junjie

2002-11-01

Oxyfluoride glasses were developed with composition 30SiO2[middle dot]15AlO1.5[middle dot]28PbF2[middle dot]22CdF2[middle dot](4.8-x)GdF3[middle dot]0.1NdF3[middle dot]0.1HoF3[middle dot]xYbF3 (x=0, 0.1, 0.2, 0.5, 1, 2, 3, 4, and 4.8) in mole percent. Powder x-ray diffraction analysis revealed that the heat treatments of the oxyfluoride glasses at 450 degC for 0.5 h cause the precipitation of Nd3+-Yb3+-Ho3+ codoped fluorite-type nanocrystals of about 16.3 nm in diameter in the glass matrix. These transparent glass ceramics exhibited very strong green up-conversion luminescence due to the Ho3+: (5F4, 5S2)[right arrow]5I8 transition under 800 nm excitation. The intensity of the green up-conversion luminescence in a 1 mol % YbF3-containing glass ceramic was found to be about 120 times stronger than that in the precursor oxyfluoride glass. The reason for the highly efficient Ho3+ up-conversion luminescence in the oxyfluoride glass ceramics is discussed. An up-conversion mechanism is also proposed.

Quantitative estimation of Nipah virus replication kinetics in vitro

PubMed Central

Chang, Li-Yen; Ali, AR Mohd; Hassan, Sharifah Syed; AbuBakar, Sazaly

2006-01-01

Background Nipah virus is a zoonotic virus isolated from an outbreak in Malaysia in 1998. The virus causes infections in humans, pigs, and several other domestic animals. It has also been isolated from fruit bats. The pathogenesis of Nipah virus infection is still not well described. In the present study, Nipah virus replication kinetics were estimated from infection of African green monkey kidney cells (Vero) using the one-step SYBR® Green I-based quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assay. Results The qRT-PCR had a dynamic range of at least seven orders of magnitude and can detect Nipah virus from as low as one PFU/μL. Following initiation of infection, it was estimated that Nipah virus RNA doubles at every ~40 minutes and attained peak intracellular virus RNA level of ~8.4 log PFU/μL at about 32 hours post-infection (PI). Significant extracellular Nipah virus RNA release occurred only after 8 hours PI and the level peaked at ~7.9 log PFU/μL at 64 hours PI. The estimated rate of Nipah virus RNA released into the cell culture medium was ~0.07 log PFU/μL per hour and less than 10% of the released Nipah virus RNA was infectious. Conclusion The SYBR® Green I-based qRT-PCR assay enabled quantitative assessment of Nipah virus RNA synthesis in Vero cells. A low rate of Nipah virus extracellular RNA release and low infectious virus yield together with extensive syncytial formation during the infection support a cell-to-cell spread mechanism for Nipah virus infection. PMID:16784519

[1,2,4]Triazolo[1,5-a]pyridine as Building Blocks for Universal Host Materials for High-Performance Red, Green, Blue and White Phosphorescent Organic Light-Emitting Devices.

PubMed

Song, Wenxuan; Shi, Lijiang; Gao, Lei; Hu, Peijun; Mu, Haichuan; Xia, Zhenyuan; Huang, Jinhai; Su, Jianhua

2018-02-14

The electron-accepting [1,2,4]triazolo[1,5-a]pyridine (TP) moiety was introduced to build bipolar host materials for the first time, and two host materials based on this TP acceptor and carbazole donor, namely, 9,9'-(2-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (o-CzTP) and 9,9'-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (m-CzTP), were designed and synthesized. These two TP-based host materials possess a high triplet energy (>2.9 eV) and appropriate highest occupied molecular orbital/lowest unoccupied molecular orbital levels as well as the bipolar transporting feature, which permits their applicability as universal host materials in multicolor phosphorescent organic light-emitting devices (PhOLEDs). Blue, green, and red PhOLEDs based on o-CzTP and m-CzTP with the same device configuration all show high efficiencies and low efficiency roll-off. The devices hosted by o-CzTP exhibit maximum external quantum efficiencies (η ext ) of 27.1, 25.0, and 15.8% for blue, green, and red light emitting, respectively, which are comparable with the best electroluminescene performance reported for FIrpic-based blue, Ir(ppy) 3 -based green, and Ir(pq) 2 (acac)-based red PhOLEDs equipped with a single-component host. The white PhOLEDs based on the o-CzTP host and three lumophors containing red, green, and blue emitting layers were fabricated with the same device structure, which exhibit a maximum current efficiency and η c of 40.4 cd/A and 17.8%, respectively, with the color rendering index value of 75.

Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

NASA Technical Reports Server (NTRS)

Wade, C. E.; Ortiz, R. M.

1997-01-01

Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

Ultra-fast and highly efficient removal of cadmium ions by magnetic layered double hydroxide/guargum bionanocomposites.

PubMed

Dinari, Mohammad; Tabatabaeian, Reyhane

2018-07-15

Finding effective methodologies for the removal of heavy metals from contaminated water are really significant. Facile and "green" techniques for adsorbents fabrication are in high demand to satisfy a wide range of practical applications. This report presents of an efficient method for preparing Fe 3 O 4 @ layered double hydroxide@ guargum bionanocomposites (GLF-BNCs). First of all, the LDH coated Fe 3 O 4 nanoparticles were simply synthesized, using ultrasonic irradiation. The citrate coated Fe 3 O 4 nanoparticles which were under negative charging and LDH nanocrystals which were charged positively make electrostatic interaction which formed a stable self-assembly component, and then guargum as a biopolymer were linked onto Fe 3 O 4 @LDH via an in situ growth method. Furthermore, the GLF-BNCs had the ability to remove cadmium ions (Cd 2+ ) from the aqueous solutions. Adsorption studies indicate that the Langmuir isotherm model and the kinetic model in pseudo-second order were appropriate for Cd(II) removal. The maximum Cd(II) adsorption capacity of the GLF8% was 258 mg g -1 . The Cd(II) was adsorbed from aqueous solutions very quickly with the contact time of 5 min by the GLF 8%, suggesting that GLF-BNCs may be a promising adsorbent for removing Cd(II) from wastewater. The effect of Fe 3 O 4 @LDH contents (2, 4 and 8 wt.%) on the thermal, physicomechanical, and morphological properties of guargum were investigated by Fourier transform infrared spectroscopy, X-ray diffraction (XRD), thermal gravimetric analysis (TGA), field emission scanning electron microscopy, transmission electron microscopy (TEM), Energy-dispersive X-ray spectroscopy and Brunauer-Emmett-Teller (BET) specific surface area techniques. The TEM results indicated that the LDH platelets are distributed within the polymer matrix. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural activity in cortical area V4 underlies fine disparity discrimination.

PubMed

Shiozaki, Hiroshi M; Tanabe, Seiji; Doi, Takahiro; Fujita, Ichiro

2012-03-14

Primates are capable of discriminating depth with remarkable precision using binocular disparity. Neurons in area V4 are selective for relative disparity, which is the crucial visual cue for discrimination of fine disparity. Here, we investigated the contribution of V4 neurons to fine disparity discrimination. Monkeys discriminated whether the center disk of a dynamic random-dot stereogram was in front of or behind its surrounding annulus. We first behaviorally tested the reference frame of the disparity representation used for performing this task. After learning the task with a set of surround disparities, the monkey generalized its responses to untrained surround disparities, indicating that the perceptual decisions were generated from a disparity representation in a relative frame of reference. We then recorded single-unit responses from V4 while the monkeys performed the task. On average, neuronal thresholds were higher than the behavioral thresholds. The most sensitive neurons reached thresholds as low as the psychophysical thresholds. For subthreshold disparities, the monkeys made frequent errors. The variable decisions were predictable from the fluctuation in the neuronal responses. The predictions were based on a decision model in which each V4 neuron transmits the evidence for the disparity it prefers. We finally altered the disparity representation artificially by means of microstimulation to V4. The decisions were systematically biased when microstimulation boosted the V4 responses. The bias was toward the direction predicted from the decision model. We suggest that disparity signals carried by V4 neurons underlie precise discrimination of fine stereoscopic depth.

Anti-CD22 and anti-CD79b antibody-drug conjugates preferentially target proliferating B cells.

PubMed

Fuh, Franklin K; Looney, Caroline; Li, Dongwei; Poon, Kirsten A; Dere, Randall C; Danilenko, Dimitry M; McBride, Jacqueline; Reed, Chae; Chung, Shan; Zheng, Bing; Mathews, William Rodney; Polson, Andrew; Prabhu, Saileta; Williams, Marna

2017-04-01

CD22 and CD79b are cell-surface receptors expressed on B-cell-derived malignancies such as non-Hodgkin's lymphoma (NHL). An anti-mitotic agent, monomethyl auristatin E, was conjugated to anti-CD22 and anti-CD79b antibodies to develop target-specific therapies for NHL. The mechanism of action (MOA) and pharmacological and pharmacokinetic (PK) profiles of these antibody-drug conjugates (ADCs) were investigated in cynomolgus monkeys. Animals were administered anti-CD22 or anti-CD79b ADCs, respective unconjugated antibodies or vehicle. Pharmacodynamic effects on total and proliferating B cells and serum PK were then assessed. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) of the ADCs were evaluated in vitro. Depletion of B cells was observed after administration of either ADC or the respective unconjugated antibodies. An extended duration of depletion was observed in animals administered ADCs. Similarly, preferential depletion of proliferating B cells in blood and germinal centre B cells in spleen were only observed in animals administered ADCs. Serum PK profiles of ADCs and respective unconjugated antibodies were comparable. In vitro, anti-human CD22 and anti-human CD79b antibodies showed no or only moderate ADCC activity, respectively; neither antibody had CDC activity. The findings support the proposed MOA: initial depletion of total B cells by antibody-mediated opsonization, followed by preferential, sustained depletion of proliferating B cells by the auristatin conjugate due to its anti-mitotic action. Delivering potent anti-mitotic agents to B cells via the specificity of monoclonal antibodies provides a means to eliminate pathogenic B cells in NHL with improved risk-benefit profiles over traditional chemotherapeutics. © 2016 Genentech. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Anti‐CD22 and anti‐CD79b antibody‐drug conjugates preferentially target proliferating B cells

PubMed Central

Fuh, Franklin K; Looney, Caroline; Li, Dongwei; Poon, Kirsten A; Dere, Randall C; Danilenko, Dimitry M; McBride, Jacqueline; Reed, Chae; Chung, Shan; Zheng, Bing; Mathews, William Rodney; Polson, Andrew; Williams, Marna

2017-01-01

Background and Purpose CD22 and CD79b are cell‐surface receptors expressed on B‐cell‐derived malignancies such as non‐Hodgkin's lymphoma (NHL). An anti‐mitotic agent, monomethyl auristatin E, was conjugated to anti‐CD22 and anti‐CD79b antibodies to develop target‐specific therapies for NHL. The mechanism of action (MOA) and pharmacological and pharmacokinetic (PK) profiles of these antibody‐drug conjugates (ADCs) were investigated in cynomolgus monkeys. Experimental Approach Animals were administered anti‐CD22 or anti‐CD79b ADCs, respective unconjugated antibodies or vehicle. Pharmacodynamic effects on total and proliferating B cells and serum PK were then assessed. Antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC) of the ADCs were evaluated in vitro. Key Results Depletion of B cells was observed after administration of either ADC or the respective unconjugated antibodies. An extended duration of depletion was observed in animals administered ADCs. Similarly, preferential depletion of proliferating B cells in blood and germinal centre B cells in spleen were only observed in animals administered ADCs. Serum PK profiles of ADCs and respective unconjugated antibodies were comparable. In vitro, anti‐human CD22 and anti‐human CD79b antibodies showed no or only moderate ADCC activity, respectively; neither antibody had CDC activity. Conclusions and Implications The findings support the proposed MOA: initial depletion of total B cells by antibody‐mediated opsonization, followed by preferential, sustained depletion of proliferating B cells by the auristatin conjugate due to its anti‐mitotic action. Delivering potent anti‐mitotic agents to B cells via the specificity of monoclonal antibodies provides a means to eliminate pathogenic B cells in NHL with improved risk–benefit profiles over traditional chemotherapeutics. PMID:28009435

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

PubMed

Kuno, S; Mizuta, E; Nishida, J; Takechi, M

1992-10-01

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

Holographic assembly of semiconductor CdSe quantum dots in polymer for volume Bragg grating structures with diffraction efficiency near 100%

NASA Astrophysics Data System (ADS)

Liu, Xiangming; Tomita, Yasuo; Oshima, Juro; Chikama, Katsumi; Matsubara, Koutatsu; Nakashima, Takuya; Kawai, Tsuyoshi

2009-12-01

We report on the fabrication of centimeter-size transmission Bragg gratings in semiconductor CdSe quantum dots dispersed 50 μm thick photopolymer films. This was done by holographic assembly of CdSe quantum dots in a photopolymerizable monomer blend. Periodic patterning of CdSe quantum dots in polymer was confirmed by a fluorescence microscope and confocal Raman imaging. The diffraction efficiency from the grating of 1 μm spacing was near 100% in the green with 0.34 vol % CdSe quantum dots, giving the refractive index modulation as large as 5.1×10-3.

Red River of the North Reconnaissance Report: Pembina River.

DTIC Science & Technology

1980-12-01

the mallard, blue -winged teal, pintail, gadwall, northern shoveler, green -winged teal, American wigeon, and redhead. [ Rush Lake receives heavy use...r.D-Ri4. 787 RED RIVER OF THE NORTH RECONNAISSANCE REPORT: PEMBINA 1/2 RIVER(IJ) GULF SOUTH RESEAPRCH INST BATON ROUGE LA DEC 9 DACU77-8@-C-e8i7B...ii% ---. :w: U ;r u --- ’w AD-A140 787 RED RIVER OF THE NORTH RECONNAISSANCE , %h,%! iREPORT , _ PEMBINA ; RIVER CD j- - D FINAL RMPORT ’ December

Oil shale resources in the Eocene Green River Formation, Greater Green River Basin, Wyoming, Colorado, and Utah

USGS Publications Warehouse

,

2011-01-01

The U.S. Geological Survey (USGS) recently completed a comprehensive assessment of in-place oil in oil shales in the Eocene Green River in the Greater Green River Basin, Wyoming, Colorado, and Utah. This CD-ROM includes reports, data, and an ArcGIS project describing the assessment. A database was compiled that includes about 47,000 Fischer assays from 186 core holes and 240 rotary drill holes. Most of the oil yield data were analyzed by the former U.S. Bureau of Mines oil shale laboratory in Laramie, Wyoming, and some analyses were made by private laboratories. Location data for 971 Wyoming oil-shale drill holes are listed in a spreadsheet and included in the CD-ROM. Total in-place resources for the three assessed units in the Green River Formation are: (1) Tipton Shale Member, 362,816 million barrels of oil (MMBO), (2) Wilkins Peak Member, 704,991 MMBO, and (3) LaClede Bed of the Laney Member, 377,184 MMBO, for a total of 1.44 trillion barrels of oil in place. This compares with estimated in-place resources for the Piceance Basin of Colorado of 1.53 trillion barrels and estimated in-place resources for the Uinta Basin of Utah and Colorado of 1.32 trillion barrels.

Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on fetal hypothyroidism in primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachrach, L.K.; Dibattista, D.; Burrow, G.N.

1983-06-01

Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of themore » DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus.« less

No Evidence for Natural Selection on Endogenous Borna-Like Nucleoprotein Elements after the Divergence of Old World and New World Monkeys

PubMed Central

Kobayashi, Yuki; Horie, Masayuki; Tomonaga, Keizo; Suzuki, Yoshiyuki

2011-01-01

Endogenous Borna-like nucleoprotein (EBLNs) elements were recently discovered as non-retroviral RNA virus elements derived from bornavirus in the genomes of various animals. Most of EBLNs appeared to be defective, but some of primate EBLN-1 to -4, which appeared to be originated from four independent integrations of bornavirus nucleoprotein (N) gene, have retained an open reading frame (ORF) for more than 40 million years. It was therefore possible that primate EBLNs have encoded functional proteins during evolution. To examine this possibility, natural selection operating on all ORFs of primate EBLN-1 to -4 was examined by comparing the rates of synonymous and nonsynonymous substitutions. The expected number of premature termination codons in EBLN-1 generated after the divergence of Old World and New World monkeys under the selective neutrality was also examined by the Monte Carlo simulation. As a result, natural selection was not identified for the entire region as well as parts of ORFs in the pairwise analysis of primate EBLN-1 to -4 and for any branch of the phylogenetic trees for EBLN-1 to -4 after the divergence of Old World and New World monkeys. Computer simulation also indicated that the absence of premature termination codon in the present-day EBLN-1 does not necessarily support the maintenance of function after the divergence of Old World and New World monkeys. These results suggest that EBLNs have not generally encoded functional proteins after the divergence of Old World and New World monkeys. PMID:21912690

No evidence for natural selection on endogenous borna-like nucleoprotein elements after the divergence of Old World and New World monkeys.

PubMed

Kobayashi, Yuki; Horie, Masayuki; Tomonaga, Keizo; Suzuki, Yoshiyuki

2011-01-01

Endogenous Borna-like nucleoprotein (EBLNs) elements were recently discovered as non-retroviral RNA virus elements derived from bornavirus in the genomes of various animals. Most of EBLNs appeared to be defective, but some of primate EBLN-1 to -4, which appeared to be originated from four independent integrations of bornavirus nucleoprotein (N) gene, have retained an open reading frame (ORF) for more than 40 million years. It was therefore possible that primate EBLNs have encoded functional proteins during evolution. To examine this possibility, natural selection operating on all ORFs of primate EBLN-1 to -4 was examined by comparing the rates of synonymous and nonsynonymous substitutions. The expected number of premature termination codons in EBLN-1 generated after the divergence of Old World and New World monkeys under the selective neutrality was also examined by the Monte Carlo simulation. As a result, natural selection was not identified for the entire region as well as parts of ORFs in the pairwise analysis of primate EBLN-1 to -4 and for any branch of the phylogenetic trees for EBLN-1 to -4 after the divergence of Old World and New World monkeys. Computer simulation also indicated that the absence of premature termination codon in the present-day EBLN-1 does not necessarily support the maintenance of function after the divergence of Old World and New World monkeys. These results suggest that EBLNs have not generally encoded functional proteins after the divergence of Old World and New World monkeys.

Hazardous Waste Water Remediation by Ecoresin-Dry Cow Dung Powder

NASA Astrophysics Data System (ADS)

Bagla, Hemlata; Barot, Nisha

2013-04-01

Water, the matter, matrix, medium and the mother of our life, is indeed one of the drivers of Nature. Through water cycle only the intra and inter equilibrium is maintained constantly between entire 'green' and 'blue'. Unfortunately, with each successive epoch of industrialization and urbanization, human societies have produced non-biodegradable waste hulk with far beyond handling capacities of mankind. At this juncture the very need is to appreciate and move towards the cost as well as time effective scientific alternatives for the removal of aqueous heavy metal pollutants. Green chemistry advocates the utilization of naturally available bio-resins which are environmentally benign alternative to current synthetic materials and technologies employed for waste water treatment. This explicit investigation aims to explore Dry Cow dung powder, DCP, a natural biosorbent as a green and clean alternative for the aqueous waste water treatment. It is naturally available bio-organic, complex, polymorphic humified fecal matter of cow and is enriched with minerals, carbohydrates, fats, proteins, bile pigments, aliphatic - aromatic species such as 'Humic acid'(HA). The HA has been successfully extracted by authors from DCP and this piece of work has been published in the International Journal [1]. We have developed simple, efficient and eco-friendly method for the removal of aqueous heavy metal pollutant such as Cr(VI) [2], Cd(II), Cr(III) [3] and Hg(II) as well radiotoxic 90Sr(II) [4], employing DCP. DCP is employed without any pre or post treatment. Being freely and easily available DCP has an edge over processed natural adsorbent considering their cost, time and energy efficiency. In nutshell we have to remember that prevention is better than the cure. If we fail to meet this, the situation will surely augment which will drain our water, our life, to slaughters knife..! Reference: 1. H.K.Bagla, N.S.Barot, Soil Amendement by Green Supplement: Dry Cowdung powder, EGUGA - 11, 515B, (2009). 2. H.K.Bagla, N.S.Barot, Adsorption studies of Cr(VI) by a Green resin : Dry Cow Dung Powder employing Tracer Technique, Radiochemica Acta, 100, pp. 1- 10, (2012). 3. H.K.Bagla,N.S.Barot, Eco-friendly waste water treatment by cow-dung powder (Adsorption studies of Cr(III), Cr (VI) & Cd(II) using Tracer Technique), Desalination & Water Treatment, 38(1-3), pp.104-113, (2012). 4. H.K.Bagla, N.S.Barot, Biosorption of Radiotoxic 90Sr by Green adsorbent: Dry Cow Dung Powder, Journal of Radioanalytical and Nuclear Chemistry, 294, pp. 81-86, (2012) .

Distribution of different surface modified carbon dots in pumpkin seedlings.

PubMed

Qian, Kun; Guo, Huiyuan; Chen, Guangcai; Ma, Chuanxin; Xing, Baoshan

2018-05-22

The distribution of surface modified carbon dots (CDs) in the pumpkin seedlings was studied by visualization techniques and their potential phytotoxicity was investigated at both the physiological and biochemical levels. The average size of carbon dots was approximately 4 nm. The fluorescent peaks of bared CDs, CD-PEI and CD-PAA were between 420 nm and 500 nm, indicating CDs could emit blue and green fluorescence. Fluorescent images showed that all three types of CDs could accumulate in the pumpkin roots and translocate to the shoots, although the distribution pattern of each CDs was obviously different. At the biochemical level, the elevated antioxidant enzymes in pumpkin roots suggest that all the CDs could potentially trigger the antioxidant defense systems in pumpkin seedlings. Additionally, such alteration was greater in the roots than in the shoots. Our study represents a new perspective on CD visualization in plant tissues and provide useful information for the potential toxicity of different types of CDs to terrestrial plants, which is of importance to agricultural application.

Fluorescent Imaging With Indocyanine Green During Laparoscopic Cholecystectomy in Patients at Increased Risk of Bile Duct Injury

PubMed Central

Ankersmit, Marjolein; van Dam, Dieuwertje A.; van Rijswijk, Anne-Sophie; van den Heuvel, Baukje; Tuynman, Jurriaan B.; Meijerink, Wilhelmus J. H. J.

2017-01-01

Background. Although rare, injury to the common bile duct (CBD) during laparoscopic cholecystectomy (LC) can be reduced by better intraoperative visualization of the cystic duct (CD) and CBD. The aim of this study was to establish the efficacy of early visualization of the CD and the added value of CBD identification, using near-infrared (NIR) light and the fluorescent agent indocyanine green (ICG), in patients at increased risk of bile duct injury. Materials and Methods. Patients diagnosed with complicated cholecystitis and scheduled for LC were included. The CBD and CD were visualized with NIR light before and during dissection of the liver hilus and at critical view of safety (CVS). Results. Of the 20 patients originally included, 2 were later excluded due to conversion. In 6 of 18 patients, the CD was visualized early during dissection and prior to imaging with conventional white light. The CBD was additionally visualized with ICG-NIR in 7 of 18 patients. In 1 patient, conversion was prevented due to detection of the CD and CBD with ICG-NIR. Conclusions. Early visualization of the CD or additional identification of the CBD using ICG-NIR in patients with complicated cholecystolithiasis can be helpful in preventing CBD injury. Future studies should attempt to establish the optimal dosage and time frame for ICG administration and bile duct visualization with respect to different gallbladder pathologies. PMID:28178882

Levofloxacin Cures Experimental Pneumonic Plague in African Green Monkeys

PubMed Central

McDonald, Jacob D.; Brasel, Trevor L.; Barr, Edward B.; Gigliotti, Andrew P.; Koster, Frederick

2011-01-01

Background Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease. Methods and Results Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3–145 (mean = 65) 50% lethal (LD50) doses of Y. pestis strain CO92. Telemetered body temperature >39°C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a “humanized” dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53–165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions. Conclusion Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen. PMID:21347450

Polyethers containing 4-(carbazol-2-yl)-7-arylbenzo[c]-1,2,5-thiadiazole chromophores as solution processed materials for hole transporting layers of OLEDs

NASA Astrophysics Data System (ADS)

Krucaite, G.; Tavgeniene, D.; Xie, Z.; Lin, X.; Zhang, B.; Grigalevicius, S.

2018-02-01

Two polyethers containing electroactive pendent 4-(carbazol-2-yl)-7-arylbenzo[c]-1,2,5-thiadiazole moieties have been synthesized by the multi-step synthetic route. Full characterization of their structures is presented. The polymers represent derivatives of very high thermal stability with initial thermal degradation temperatures of 425 °C and 431 °C. Glass transition temperatures of the amorphous materials were also very high and reached values of 154 °C and 163 °C. The electron photoemission spectra of thin layers of the polymers showed ionization potentials of 5.84 eV and 5.93 eV. Hole-transporting properties of the polymeric materials were tested in the structures of organic light emitting diodes with Alq3 as the green emitter and electron transporting material. An electroluminescent device containing hole-transporting layer (HTL) of the polymer with electroactive 4-carbazolyl-7-phenylbenzo[c]-1,2,5-thiadiazole moieties exhibited turn on voltage of 6.2 V, maximum photometric efficiency of 2.5 cd/A and maximum brightness exceeding 300 cd/m2. The device containing HTL of the polymer with 4-carbazolyl-7-(1-naphtyl)benzo[c]-1,2,5-thiadiazole moieties demonstrated turn on voltage of 5.2 V, maximum photometric efficiency of 1.6 cd/A and maximum brightness exceeding 1500 cd/m2. The efficiencies were about 30-90% higher than that of the device containing widely used hole transporting layers of poly(9-vinylcarbazole).

Effects of local myopic defocus on refractive development in monkeys.

PubMed

Smith, Earl L; Hung, Li-Fang; Huang, Juan; Arumugam, Baskar

2013-11-01

Visual signals that produce myopia are mediated by local, regionally selective mechanisms. However, little is known about spatial integration for signals that slow eye growth. The purpose of this study was to determine whether the effects of myopic defocus are integrated in a local manner in primates. Beginning at 24 ± 2 days of age, seven rhesus monkeys were reared with monocular spectacles that produced 3 diopters (D) of relative myopic defocus in the nasal visual field of the treated eye but allowed unrestricted vision in the temporal field (NF monkeys). Seven monkeys were reared with monocular +3 D lenses that produced relative myopic defocus across the entire field of view (FF monkeys). Comparison data from previous studies were available for 11 control monkeys, 8 monkeys that experienced 3 D of hyperopic defocus in the nasal field, and 6 monkeys exposed to 3 D of hyperopic defocus across the entire field. Refractive development, corneal power, and axial dimensions were assessed at 2- to 4-week intervals using retinoscopy, keratometry, and ultrasonography, respectively. Eye shape was assessed using magnetic resonance imaging. In response to full-field myopic defocus, the FF monkeys developed compensating hyperopic anisometropia, the degree of which was relatively constant across the horizontal meridian. In contrast, the NF monkeys exhibited compensating hyperopic changes in refractive error that were greatest in the nasal visual field. The changes in the pattern of peripheral refractions in the NF monkeys reflected interocular differences in vitreous chamber shape. As with form deprivation and hyperopic defocus, the effects of myopic defocus are mediated by mechanisms that integrate visual signals in a local, regionally selective manner in primates. These results are in agreement with the hypothesis that peripheral vision can influence eye shape and potentially central refractive error in a manner that is independent of central visual experience.

Behavioral Determinants of Cannabinoid Self-Administration in Old World Monkeys.

PubMed

John, William S; Martin, Thomas J; Nader, Michael A

2017-06-01

Reinforcing effects of Δ 9 -tetrahydrocannabinol (THC), the primary active ingredient in marijuana, as assessed with self-administration (SA), has only been established in New World primates (squirrel monkeys). The objective of this study was to investigate some experimental factors that may enhance intravenous SA of THC and the cannabinoid receptor (CBR) agonist CP 55 940 in Old World monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. In one experiment, male rhesus monkeys (N=9) were trained to respond under a fixed-ratio 10 schedule of food presentation. The effects of CP 55 940 (1.0-10 μg/kg, i.v.) and THC (3.0-300 μg/kg, i.v.) on food-maintained responding and body temperature were determined in these subjects prior to giving them access to self-administer each drug. Both drugs dose-dependently decreased food-maintained responding. CP 55 940 (0.001-3.0 μg/kg) functioned as a reinforcer in three monkeys, whereas THC (0.01-10 μg/kg) did not have reinforcing effects in any subject. CP 55 940 was least potent to decrease food-maintained responding in the monkeys in which CP 55 940 functioned as a reinforcer. Next, THC was administered daily to monkeys until tolerance developed to rate-decreasing effects. When THC SA was reexamined, it functioned as a reinforcer in three monkeys. In a group of cocaine-experienced male cynomolgus monkeys (N=4), THC SA was examined under a second-order schedule of reinforcement; THC functioned as reinforcer in two monkeys. These data suggest that SA of CBR agonists may be relatively independent of their rate-decreasing effects in Old World monkeys. Understanding individual differences in vulnerability to THC SA may lead to novel treatment strategies for marijuana abuse.

Stock optimizing in choice when a token deposit is the operant.

PubMed

Widholm, J J; Silberberg, A; Hursh, S R; Imam, A A; Warren-Boulton, F R

2001-11-01

Each of 2 monkeys typically earned their daily food ration by depositing tokens in one of two slots. Tokens deposited in one slot dropped into a bin where they were kept (token kept). Deposits to a second slot dropped into a bin where they could be obtained again (token returned). In Experiment 1, a fixed-ratio (FR) 5 schedule that provided two food pellets was associated with each slot. Both monkeys preferred the token-returned slot. In Experiment 2, both subjects chose between unequal FR schedules with the token-returned slot always associated with the leaner schedule. When the FRs were 2 versus 3 and 2 versus 6, preferences were maintained for the token-returned slot; however, when the ratios were 2 versus 12, preference shifted to the token-kept slot. In Experiment 3, both monkeys chose between equal-valued concurrent variable-interval variable-interval schedules. Both monkeys preferred the slot that returned tokens. In Experiment 4, both monkeys chose between FRs that typically differed in size by a factor of 10. Both monkeys preferred the FR schedule that provided more food per trial. These data show that monkeys will choose so as to increase the number of reinforcers earned (stock optimizing) even when this preference reduces the rate of reinforcement (all reinforcers divided by session time).

Evaluation of bendectin embryotoxicity in nonhuman primates: I. Ventricular septal defects in prenatal macaques and baboon.

PubMed

Hendrickx, A G; Cukierski, M; Prahalada, S; Janos, G; Rowland, J

1985-10-01

Cynomolgus monkeys, rhesus monkeys and baboons were administered 10 to 40 times the human dose equivalent of Bendectin throughout the major period of organogenesis (22(+/-3)-50 days of gestation). In animals examined prenatally (100 +/- 2 days gestation) the total incidence of ventricular septal defects (VSD) was 40% in cynomolgus monkeys, 18% in rhesus monkeys, and 23% in baboons. The majority of VSD involved the muscular portion of the septum. No dose response was evident and there were no other cardiac or extracardiac defects found except for one baboon fetus with multiple defects. No defects were observed in cynomolgus monkeys administered Bendectin for 4-day periods between 22 and 41 days of gestation. There was no association of Bendectin treatment with any noncardiac defect. In cynomolgus and rhesus monkeys examined at term there was one mitral valve defect and no incidence of VSD. The increased incidence of VSD observed prenatally in all three species and the absence of defects in macaques at term suggests a delay in closure of the ventricular septum in treated animals. The Bendectin-treated monkey may be a suitable model for the study of the pathogenesis of VSD and the mechanism of spontaneous closure of the defect.

Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

PubMed

Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer

2005-02-08

Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

Influence of Shell Thickness on the Performance of NiO-Based All-Inorganic Quantum Dot Light-Emitting Diodes.

PubMed

Wang, Ting; Zhu, Bingyan; Wang, Shuangpeng; Yuan, Qilin; Zhang, Han; Kang, Zhihui; Wang, Rong; Zhang, Hanzhuang; Ji, Wenyu

2018-05-02

The effect of shell thickness on the performance of all-inorganic quantum dot light-emitting diodes (QLEDs) is explored by employing a series of green quantum dots (QDs) (Zn x Cd 1- x Se/ZnS core/shell QDs with different ZnS shell thicknesses) as the emitters. ZnO nanoparticles and sol-gel NiO are employed as the electron and hole transport materials, respectively. Time-resolved and steady-state photoluminescence results indicate that positive charging processes might occur for the QDs deposited on NiO, which results in emission quenching of QDs and poor device performance. The thick shell outside the core in QDs not only largely suppresses the QD emission quenching but also effectively preserves the excitons in QDs from dissociation of electron-hole pairs when they are subjected to an electric field. The peak efficiency of 4.2 cd/A and maximum luminance of 4205 cd/m 2 are achieved for the device based on QDs with the thickest shells (∼4.2 nm). We anticipate that these results will spur progress toward the design and realization of efficient all-inorganic QLEDs as a platform for the QD-based full-colored displays.

Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days.

PubMed

Schild, Laura J; Divi, Rao L; Beland, Frederick A; Churchwell, Mona I; Doerge, Daniel R; Gamboa da Costa, Gonçalo; Marques, M Matilde; Poirier, Miriam C

2003-09-15

The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides), whereas brain cortex DNA contained lower adduct levels (0.6-4.8 adducts/10(8) nucleotides) and the lowest levels were measured in the kidney (0.2-0.4 adducts/10(8) nucleotides). This study indicates that cynomolgus monkeys are capable of metabolizing TAM to genotoxic intermediates that form TAM-DNA adducts in multiple tissues.

Isolation, propagation, and characterization of a second equine rotavirus serotype.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

A rotavirus designated strain H-2 was isolated in primary African green monkey kidney cells from a foal with diarrhea. This cell culture-adapted strain was found to be similar, if not identical, to simian rotavirus (strains MMU18006 and SA-11) and canine rotavirus (strain CU-1) and, in addition, demonstrated a one-way antigenic relationship with five human rotavirus strains (P, B, no. 14, no. 15, and YO) of the third human rotavirus serotype by the plaque reduction neutralization test. This is the fifth example of an animal rotavirus which shares serotypic specificity with a human rotavirus. The H-2 strain is distinct from the H-1 strain (Y. Hoshino et al., J. Clin. Microbiol., in press) of equine rotavirus not only in serotypic specificity by neutralization but also in subgroup specificity, hemagglutinating activity, and RNA electrophoretic migration pattern, thus establishing the existence of a second equine rotavirus serotype. This H-2 isolate is also distinct by neutralization from three other human rotavirus serotypes, 1 (Wa), 2 (DS-1), and 4 (St. Thomas no. 4), as well as bovine (NCDV), and porcine (OSU) rotaviruses. Images PMID:6309657

Topical and intravenous pilocarpine stimulated accommodation in anesthetized rhesus monkeys.

PubMed

Wendt, Mark; Glasser, Adrian

2010-05-01

Many studies have used pilocarpine to stimulate accommodation in both humans and monkeys. However, the concentrations of pilocarpine used and the methods of administration vary. In this study, three different methods of pilocarpine administration are evaluated for their effectiveness in stimulating accommodation in rhesus monkeys. Experiments were performed in 17 iridectomized, anesthetized rhesus monkeys aged 4-16 years. Maximum accommodation was stimulated in all these monkeys with a 2% pilocarpine solution maintained on the cornea for at least 30 min in a specially designed perfusion lens. In subsequent topical pilocarpine experiments, baseline refraction was measured with a Hartinger coincidence refractometer and then while the monkeys were upright and facing forward, commercially available pilocarpine (2, 4, or 6%) was applied topically to the cornea as 2 or 4 drops in two applications or 6 drops in three applications over a five minute period with the eyelids closed between applications. Alternatively, while supine, 10-12 drops of pilocarpine were maintained on the cornea in a scleral cup for 5 min. Refraction measurements were begun 5 min after the second application of pilocarpine and continued for at least 30 min after initial administration until no further change in refraction occurred. In intravenous experiments, pilocarpine was given either as boluses ranging from 0.1mg/kg to 2mg/kg or boluses followed by a constant infusion at rates between 3.06 mg/kg/h and 11.6 mg/kg/h. Constant 2% pilocarpine solution on the eye in the perfusion lens produced 10.88+/-2.73 D (mean+/-SD) of accommodation. Topically applied pilocarpine produced 3.81 D+/-2.41, 5.49 D+/-4.08, and 5.55 D+/-3.27 using 2%, 4%, and 6% solutions respectively. When expressed as a percentage of the accommodative response amplitude obtained in the same monkey with constant 2% pilocarpine solution on the eye, the responses were 34.7% for 2% pilocarpine, 48.4% for 4% pilocarpine, and 44.6% for 6% pilocarpine. Topical 4% and 6% pilocarpine achieved similar, variable accommodative responses, but neither achieved maximum accommodation. IV boluses of pilocarpine achieved near maximal levels of accommodation at least ten times faster than topical methods. Doses effective for producing maximum accommodation ranged from 0.25mg/kg to 1.0mg/kg. IV pilocarpine boluses caused an anterior movement of the anterior lens surface, a posterior movement of the posterior lens surface, and a slight net anterior movement of the entire lens. Considerable variability in response amplitude occurred and maximum accommodative amplitude was rarely achieved with topical application of a variety of concentrations of commercially available pilocarpine. Intravenous infusion of pilocarpine was a rapid and reliable method of producing a nearly maximal accommodative response and maintaining accommodation when desired. (c) 2010 Elsevier Ltd. All rights reserved.

Marmoset Cytochrome P450 3A4 Ortholog Expressed in Liver and Small-Intestine Tissues Efficiently Metabolizes Midazolam, Alprazolam, Nifedipine, and Testosterone.

PubMed

Uehara, Shotaro; Uno, Yasuhiro; Nakanishi, Kazuyuki; Ishii, Sakura; Inoue, Takashi; Sasaki, Erika; Yamazaki, Hiroshi

2017-05-01

Common marmosets ( Callithrix jacchus ), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has not investigated in marmosets. In this study, sequence homology, tissue distribution, and enzymatic properties of marmoset P450 3A4 ortholog, 3A5 ortholog, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologs and evolutionary closeness to human and cynomolgus monkey P450 3A orthologs compared with other P450 3A enzymes. Among the five marmoset tissues examined, P450 3A4 ortholog mRNA was abundant in livers and small intestines where P450 3A4 ortholog proteins were immunologically detected. Three marmoset P450 3A proteins heterologously expressed in Escherichia coli membranes catalyzed midazolam 1'- and 4-hydroxylation, alprazolam 4-hydroxylation, nifedipine oxidation, and testosterone 6 β -hydroxylation, similar to cynomolgus monkey and human P450 3A enzymes. Among the marmoset P450 3A enzymes, P450 3A4 ortholog effectively catalyzed midazolam 1'-hydroxylation, comparable to microsomes from marmoset livers and small intestines. Correlation analyses with 23 individual marmoset liver microsomes suggested contributions of P450 3A enzymes to 1'-hydroxylation of both midazolam (human P450 3A probe) and bufuralol (human P450 2D6 probe), similar to cynomolgus monkey P450 3A enzymes. These results indicated that marmoset P450 3A forms had functional characteristics roughly similar to cynomolgus monkeys and humans in terms of tissue expression patterns and catalytic activities, suggesting marmosets as suitable animal models for P450 3A-dependent drug metabolism. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Patterned mist deposition of tri-colour CdSe/ZnS quantum dot films toward RGB LED devices

NASA Astrophysics Data System (ADS)

Pickering, S.; Kshirsagar, A.; Ruzyllo, J.; Xu, J.

2012-06-01

In this experiment a technique of mist deposition was explored as a way to form patterned ultra-thin-films of CdSe/ZnS core/shell nanocrystalline quantum dots using colloidal solutions. The objective of this study was to investigate the feasibility of mist deposition as a patterning method for creating multicolour quantum dot light emitting diodes. Mist deposition was used to create three rows of quantum dot light emitting diodes on a single device with each row having a separate colour. The colours chosen were red, green and yellow with corresponding peak wavelengths of 620 nm, 558 nm, and 587 nm. The results obtained from this experiment show that it is possible to create multicolour devices on a single substrate. The peak brightnesses obtained in this experiment for the red, green, and yellow were 508 cd/m, 507 cd/m, and 665 cd/m, respectively. The similar LED brightness is important in display technologies using colloidal quantum dots in a precursor solution to ensure one colour does not dominate the emitted spectrum. Results obtained in-terms of brightness were superior to those achieved with inkjet deposition. This study has shown that mist deposition is a viable method for patterned deposition applied to quantum dot light emitting diode display technologies.