| 1. |
- Chen, Zhen, et al.
(författare)
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Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH)
- 2020
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier. - 0960-894X .- 1464-3405. ; 30:21
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information. So far, most PET tracers show irreversible binding patterns with FAAH, which would result in complicated quantitative processes. Herein, we have identified a new FAAH inhibitor (1-((1-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)(oxazol-2-yl)methanone (8) which inhibits the hydrolysis of AEA in the brain with high potency (IC50 value 11 nM at a substrate concentration of 0.5 µM), and without showing time-dependency. The PET tracer [11C]8 (also called [11C]FAAH-1906) was successfully radiolabeled with [11C]MeI in 17 ± 6% decay-corrected radiochemical yield (n = 7) with >74.0 GBq/μmol (2 Ci/μmol) molar activity and >99% radiochemical purity. Ex vivo biodistribution and blocking studies of [11C]8 in normal mice were also conducted, indicating good brain penetration, high brain target selectivity, and modest to excellent target selectivity in peripheral tissues. Thus, [11C]8 is a potentially useful PET ligand with enzyme inhibitory and target binding properties consistent with a reversible mode of action.
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| 2. |
- Pettersson, Fredrik, et al.
(författare)
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Whole-body imaging of sequestration of Plasmodium falciparum in the rat.
- 2005
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Ingår i: Infect Immun. - 0019-9567. ; 73:11, s. 7736-46
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Tidskriftsartikel (refereegranskat)abstract
- The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99mtechnetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal. iRBC of different lines and clones sequester avidly in vivo while uninfected erythrocytes did not. Histological examination revealed that a multiadhesive parasite adhered in the larger microvasculature, inducing extensive intravascular changes while CD36- and chondroitin sulfate A-specific parasites predominantly sequester in capillaries, inducing no or minor pathology. Removal of the adhesive ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), preincubation of the iRBC with sera to PfEMP1 or preincubation with soluble PfEMP1-receptors prior to injection significantly reduced the sequestration. The specificity of iRBC binding to the heterologous murine receptors was confirmed in vitro, using primary rat lung endothelial cells and rat lung cryosections. In offering flow dynamics, nonmanipulated endothelial cells, and an intact immune system, we believe this syngeneic animal model to be an important complement to existing in vitro systems for the screening of vaccines and adjunct therapies aiming at the prevention and treatment of severe malaria.
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| 3. |
- Ren, Qijun, et al.
(författare)
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Evidence for coupling between exciton emissions and surface plasmon in Ni-coated ZnO nanowires
- 2012
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Ingår i: Nanotechnology. - : Institute of Physics Publishing (IOPP). - 0957-4484 .- 1361-6528. ; 23:42, s. 425201-
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Tidskriftsartikel (refereegranskat)abstract
- We show that coating ZnO nanowires (NWs) with a transition metal, such as Ni, can increase the efficiency of light emission at room temperature. Based on detailed structural and optical studies, this enhancement is attributed to energy transfer between near-band-edge emission in ZnO and surface plasmons in the Ni film which leads to an increased rate of the spontaneous emission. It is also shown that the Ni coating leads to an enhanced non-radiative recombination via surface states, which becomes increasingly important at low measurement temperatures and in annealed ZnO/Ni NWs.
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| 4. |
- Ahuja, Sanjay, et al.
(författare)
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Prediction of solubility on recombinant expression of Plasmodium falciparum erythrocyte membrane protein I domains in Escherichia coli
- 2006
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Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cellular interactions elicited by Plasmodium falciparum erythrocyte membrane protein antigen 1 (PfEMP1) are brought about by multiple DBL ( Duffy binding like), CIDR ( cysteine-rich interdomain region) and C2 domain types. Elucidation of the functional and structural characteristics of these domains is contingent on the abundant availability of recombinant protein in a soluble form. A priori prediction of PfEMP1 domains of the 3D7 genome strain, most likely to be expressed in the soluble form in Escherichia coli was computed and proven experimentally. Methods: A computational analysis correlating sequence-dependent features to likelihood for expression in soluble form was computed and predictions were validated by the colony filtration blot method for rapid identification of soluble protein expression in E. coli. Results: Solubility predictions for all constituent PfEMP1 domains in the decreasing order of their probability to be expressed in a soluble form (% mean solubility) are as follows: ATS (56.7%) > CIDR1 alpha (46.8%) > CIDR2 beta (42.9%) > DBL2-4 gamma (31.7%) > DBL2 beta + C2 (30.6%) > DBL1 alpha (24.9%) > DBL2-7 epsilon (23.1%) > DBL2-5 delta (14.8%). The length of the domains does not correlate to their probability for successful expression in the soluble form. Immunoblot analysis probing for soluble protein confirmed the differential in solubility predictions. Conclusion: The acidic terminal segment ( ATS) and CIDR alpha/beta domain types are suitable for recombinant expression in E. coli while all DBL subtypes (alpha, beta, gamma, delta, epsilon) are a poor choice for obtaining soluble protein on recombinant expression in E. coli. This study has relevance for researchers pursuing functional and structural studies on PfEMP1 domains.
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| 5. |
- Albrecht, Letusa, et al.
(författare)
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var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.2
- 2011
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Ingår i: Malaria Journal. - : BioMed Central. - 1475-2875 .- 1475-2875. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.
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| 6. |
- Balogun, Halima A., et al.
(författare)
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Pattern of antibodies to the Duffy binding like domain of Plasmodium falciparum antigen Pf332 in Senegalese individuals
- 2014
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Ingår i: Acta Tropica. - : Elsevier BV. - 0001-706X .- 1873-6254. ; 130, s. 80-87
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Tidskriftsartikel (refereegranskat)abstract
- Acquisition of antibodies against blood stage antigens is crucial in malaria immunity and the Plasmodium falciparum antigen Pf332, which is present in close association with the infected red blood cell membrane, is one such antigen. In this study, the antibody response to a Duffy binding like fragment of Pf332, termed Pf332-DBL was investigated in sera from naturally exposed individuals living in Dielmo village, Senegal, with regard to immunoglobulin classes (IgG, IgM, IgE) and IgG subclasses (IgG1-4). While the levels of IgM, IgG, IgG1 and IgG2 only displayed a moderate trend to increase with age, Pf332-DBL specific IgG3 levels increased significantly in the older villagers. In multivariate analysis, when controlling for confounding factors, and in a linear model with a Poisson distribution, anti-Pf332-DBL IgG3 as well as the ratio of cytophilic to non cytophilic anti-Pf332-DBL antibodies were found significantly associated with a reduced risk of malaria attack. This association was also present when the IgG3:IgG1 ratio was tested. Finally, two subgroups of villagers with the same mean age, were delineated by IgG3 concentrations either lower or higher than the median value. A total of 45.2% of the individuals with low anti-Pf332-DBL-IgG3 levels but only 21.4% of the villagers in the group with high levels of such antibodies had a clinical malaria attack during a period of 3 years of continuous follow-up after the blood sampling. In conclusion, Pf332-DBL induces naturally the acquisition of antibodies, and Pf332-DBL-specific IgG3 appears to be associated with protection against malaria in this endemic setting.
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| 7. |
- Brolin, M, et al.
(författare)
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Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites
- 2009
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 10:10, s. R117-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Single nucleotide polymorphisms are common in duplicated genes, causing functional preservation, alteration or silencing. The Plasmodium falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the HB3 parasite line. Whereas the molecular function of Pf332 remains to be elucidated, VAR2CSA is known to be the main adhesin in placental parasite sequestration. Sequence variations introduced upon duplication of these genes provide discriminative possibilities to analyze allele-specific transcription with a bearing towards understanding gene dosage impact on parasite biology. Results: We demonstrate an approach combining real-time PCR allelic discrimination and discriminative RNA-FISH to distinguish between highly similar gene copies in P. falciparum parasites. The duplicated var2csa variants are simultaneously transcribed, both on a population level and intriguingly also in individual cells, with nuclear co-localization of the active genes and corresponding transcripts. This indicates transcriptional functionality of duplicated genes, challenges the dogma of mutually exclusive var gene transcription and suggests mechanisms behind antigenic variation, at least in respect to the duplicated and highly similar var2csa genes. Conclusions: Allelic discrimination assays have traditionally been applied to study zygosity in diploid genomes. The assays presented here are instead successfully applied to the identification and evaluation of transcriptional activity of duplicated genes in the haploid genome of the P. falciparum parasite. Allelic discrimination and gene or transcript localization by FISH not only provide insights into transcriptional regulation of genes such as the virulence associated var genes, but also suggest that this sensitive and precise approach could be used for further investigation of genome dynamics and gene regulation.
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| 8. |
- Hao, Jiaming, et al.
(författare)
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Manipulate light polarizations by metamaterials : From microwave to optics
- 2008
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Ingår i: PROCEEDINGS OF THE 2008 INTERNATIONAL WORKSHOP ON METAMATERIALS. - NEW YORK : IEEE. ; , s. 89-89
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Konferensbidrag (refereegranskat)abstract
- Recently, artificially designed metamaterials have become of considerable interests, because they exhibit extraordinary optical characteristics that do not exist in nature and promise many potential applications, such as negative refraction, subwavelength imaging, and electromagnetic invisibility cloaking. Although creating metamaterials at the optical frequency range faces numerous technological challenges, such materials with particular properties have been realized gradually based on new device concepts. In this talk, we present our efforts to employ specific metamaterials to manipulate the polarization states of incident lights, in both microwave [1, 2] and optical frequency regimes [3]. Experimental results reveal that the maximum polarization conversion ratio (PGR) value can reach 100% in microwave regime (see left figure below) and 92% in optical frequency (see right figure blow) under certain conditions. Theoretical studies combined with numerical simulations show that the governing physics is dominated by the unique reflection properties of the metamaterials
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| 9. |
- Hao, Jiaming, et al.
(författare)
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Optical metamaterial for polarization control
- 2009
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 80:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the design, characterization, and modeling of a specific optical metamaterial, and employ it to manipulate the light polarizations at optical frequencies. Experimental results reveal that the maximum polarization conversion efficiency, i.e., the energy portion converted from s to p polarization after reflection, can be as high as 96% at the wavelength of similar to 685 nm. Simulations and analytical results, which are in reasonable agreements with the experimental results, reveal that the underlying physics are governed by the particular electric and magnetic resonances in the optical metamaterial.
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| 10. |
- Koval'chuk, Andrii, et al.
(författare)
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Polymer Matrix Role in Light Absorption and Emission by Nano-CdS/PVA Composite
- 2013
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Konferensbidrag (refereegranskat)abstract
- Influence of a polymeric medium on the light absorption and emissionprocesses of composite nano-CdS/polyvinyl alcohol is studied by activating different absorption-emission routes via changing of excitation wavelengths. The mechanisms are analyzed by employing the time-resolved photoluminescence spectroscopy. It is shown that thepolymeric component of the composite contributes mainly to the excitation processes of photoluminescence via absorption of external laser excitation and its following transfer to the CdS nanoparticles that are incorporated into polymer matrix. The composite emission occurs mostly within the nanoparticles. It is also shown that time-decays of the photoluminescence emission from the CdS nanoparticles embedded in the composite depend on the excitation wavelength. Such behavior is ascribed to the interplay between the intrinsic nanoparticles excitation and extrinsic feeding of the nanoparticles via energy transfer from the excited polymer matrix. Possible mechanisms of the observed energy transfer are also discussed.
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