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1.
Mohammed Marunnan Sahila Pallikkara Pulikkal Babitha Srinivas Bandaru Anuraj Nayarisseri Victor Arokia Doss 《Bioinformation》2015,11(6):280-289
The present antipsychotic drugs have known to show serious concerns like extra pyramidal side effects therefore, pursuit for novel
antipsychotic GABAnergic drugs has lately focused on the folkloric medicine from plant derivatives as better treatment option of
schizophrenia. The present study centers to identify potential inhibitors of plant origin for GABA receptor through in silico
approaches. Three compound datasets were undertaken in the study. The first set consisted of seven compounds which included
Magnolol, Honokiol and other plant derivatives. The second set consisted of 16 derivatives of N-diarylalkenyl-piperidinecarboxylic
acid synthesized by Zheng et al., 2006. The third dataset had thirty two compounds which were Magnolol and Honokiol analogues
synthesized by Fuchs et al., 2014. All the compounds were docked at the allosteric site of the GABA (A) receptor. The compounds
were further tested for ADMET and biological activity. We observed Honokiol and its derivatives demonstrated superior druglike
properties than any compound undertaken in the study. Further, compound 61 [2-(4-methoxyphenyl)-4-propylphenol] of dataset
three - a synthetic derivative of honokiol had better profile than its parent compound. In a possible attempt to identify compound
with even better efficacious compound than 61, virtual screening was performed, 135 compounds akin to compound 61 were
retrieved. Interestingly none of the 135 compounds showed better druggable properties than compound 61. Our in silico
pharmacological profiling of compounds is in coherence and is complemented by the findings of Fuchs et al, which also revealed
compound 61 to be the good potentiator of GABA receptor.
Abbreviations
GABA (A) R - Gamma Amino Butyric Acid Receptor, subtype A, GPCR - G Protein Coupled Receptor, OPLS - Optimized Potentials for Liquid Simulations, PDB - Protein Data Bank, PLP - Piece wise Linear Potential, T.E.S.T - Toxicity Estimation Software Tool, TCM - Traditional Chinese Medicine. 相似文献2.
Behnam Rashidieh Sarah Etemadiafshar Golnaz Memari Masoumeh Mirzaeichegeni Shahrzad Yazdi Fatemeh Farsimadan Soodabeh Alizadeh 《Bioinformation》2015,11(8):373-377
Staphylococcus aureus, a Gram-positive bacterium is pathogenic in nature. It is known that secreted toxins remain active after
antibiotic treatment. The alpha hemolysin or alpha toxin damages cell membrane and induces apoptosis and degradation of DNA.
The titer of alphahemolysin increases and causes hemostasis disturbances, thrombocytopenia, and pulmonary lesions during
staphylococcal infection. Therefore, it is of interest to inhibit alpha hemolysin using novel compounds. We used the structure of
alpha hemolysin(PDB: 7AHL) to screen structures for 100,000 compounds from the ZINC database using molecular docking with
AutoDock VINA. Nine (9) successive hits were then subjected for pharmacokinetic and toxicity properties by PROTOX (a
webserver for the prediction of oral toxicities of small molecules) and FAFDrugs (a tool for prediction of ADME and Toxicity). This
exercise further identified hit #1 ({[3a-(Dihydroxymethyl)-6-hydroxy-2,2-dimethyl-1,3,4-trioxatetrahydro-2H-pentalen-5-
yl]methyl}amino(9H-fluoren-9-yl)acetate with binding affinity: -10.3 kcal/mol) and hit #2 (6-(Dihydroxymethyl)-2-{2-[3-
(methylamino)propyl]-2-azatricyclo[9.4.0.03,8]pentadeca-1(11),3,5,7,12,14-hexaen-6-yloxy}tetrahydro-2H-pyran-3,4,5-triol with
binding affinity: -9.6 kcal/mol) with acceptable toxicity and ADME properties for potential predicted hemolysin inhibition. These
compounds should then be evaluated in vitro using inhibitory studies. 相似文献
3.
Abdullahi Ibrahim Uba 《Journal of biomolecular structure & dynamics》2013,31(14):3627-3636
AbstractHistone deacetylases (HDACs) are implicated in the pathology of various cancers, and their pharmacological blockade has proven to be promising in reversing the malignant phenotypes. However, lack of crystal structures of some of the human HDAC isoforms (e.g., HDAC10) hinders the design of the isoform-selective inhibitor. Here, the recently solved X-ray crystal structure of Danio rerio (zebrafish) HDAC10 (Protein Data Bank (PDB) ID; 5TD7, released on 24 May 2017) was retrieved from the PDB and used as a template structure to model the three-dimensional structure of human HDAC10. The overall quality of the best model (M0017) was assessed by computing its z-score—a measure of the deviation of the total energy of the structure with respect to an energy distribution derived from random conformations and by docking of known HDAC10 inhibitors to its catalytic cavity. Furthermore, to identify potential HDAC10-selective inhibitor ligand-based virtual screening was carried out against the ZINC database. The free modeled structure of HDAC10 and its complexes with quisinostat and the highest-ranked compound ZINC19749069 were submitted to molecular dynamics simulation. The comparative analysis of root-mean-squared deviation, root-mean-squared fluctuation, radius of gyration (Rg), and potential energy of these systems showed that HDAC10-ZINC19749069 complex remained the most stable over time. Thus, M0017 could be potentially used for structure-based inhibitor against HDAC10, and ZINC19749069 may provide a scaffold for further optimization.Communicated by Ramaswamy H. Sarma 相似文献
4.
Mary Bushman Lindsay Morton Nancy Duah Neils Quashie Benjamin Abuaku Kwadwo A. Koram Pedro Rafael Dimbu Mateusz Plucinski Julie Gutman Peter Lyaruu S. Patrick Kachur Jacobus C. de Roode Venkatachalam Udhayakumar 《Proceedings. Biological sciences / The Royal Society》2016,283(1826)
Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures. 相似文献
5.
Curtidor H Rodríguez LE Ocampo M López R García JE Valbuena J Vera R Puentes A Vanegas M Patarroyo ME 《Protein science : a publication of the Protein Society》2005,14(2):464-473
Erythrocyte binding ligand 1 (EBL-1) is a member of the ebl multigene family involved in Plasmodium falciparum invasion of erythrocytes. We found that five EBL-1 high-activity binding peptides (HABPs) bound specifically to erythrocytes: 29895 ((41)HKKKSGELNNNKSGILRSTY(60)), 29903 ((201)LYECGK-KIKEMKWICTDNQF(220)), 29923 ((601)CNAILGSYADIGDIVRGLDV(620)), 29924((621)WRDINTNKLSEK-FQKIFMGGY(640)), and 30018 ((2481)LEDIINLSKKKKKSINDTSFY(2500)). We also show that binding was saturable, not sialic acid-dependent, and that all peptides specifically bound to a 36-kDa protein on the erythrocyte membrane. The five HABPs inhibited in vitro merozoite invasion depending on the peptide concentration used, suggesting their possible role in the invasion process. 相似文献
6.
Rajan Pandey Rakesh Kumar Priya Gupta Asif Mohmmed Rita Tewari Pawan Malhotra 《Journal of biomolecular structure & dynamics》2013,31(13):3531-3540
Kinases and phosphatases are involved in many essential processes in Plasmodium lifecycle. Among the identified 67 Plasmodium falciparum phosphatases, Phosphatase of Regenerating Liver (PRL) family protein homolog, PfPRL, is an essential parasite tyrosine phosphatase. PfPRL is shown to be prenylated, secreted, and involved in the host invasion process. In the present study, a structure-based high throughput in silico screening of PfPRL binders, using ChEMBL-NTD compounds lead to the identification of nine compounds based on binding energy, Lipinski rule of five, and QED score. The most of the shortlisted compounds are known to inhibit parasite growth at a concentration (EC50) ≤2 μm in in vitro P. falciparum culture assays. MD simulations were carried out on the shortlisted nine potential enzyme–inhibitor complexes to analyze specificity, stability, and to calculate the free binding energies of the complexes. The study identifies PfPRL as one of the potential drug targets for selected ChEMBL-NTD compounds that may be exploited as a scaffold to develop novel antimalarials. 相似文献
7.
Denise Patricia Mawili-Mboumba Noé Mbondoukwe Elvire Adande Marielle Karine Bouyou-Akotet 《The Korean journal of parasitology》2015,53(4):413-419
The present study determined and compared the genetic diversity of Plasmodium falciparum strains infecting children living in 2 areas from Gabon with different malaria endemicity. Blood samples were collected from febrile children from 2008 to 2009 in 2 health centres from rural (Oyem) and urban (Owendo) areas. Genetic diversity was determined in P. falciparum isolates by analyzing the merozoite surface protein-1 (msp1) gene polymorphism using nested-PCR. Overall, 168 children with mild falciparum malaria were included. K1, Ro33, and Mad20 alleles were found in 110 (65.5%), 94 (55.9%), and 35 (20.8%) isolates, respectively, without difference according to the site (P>0.05). Allelic families’ frequencies were comparable between children less than 5 years old from the 2 sites; while among the older children the proportions of Ro33 and Mad20 alleles were 1.7 to 2.0 fold higher at Oyem. Thirty-three different alleles were detected, 16 (48.5%) were common to both sites, and 10 out of the 17 specific alleles were found at Oyem. Furthermore, multiple infection carriers were frequent at Oyem (57.7% vs 42.2% at Owendo; P=0.04) where the complexity of infection was of 1.88 (±0.95) higher compared to that found at Owendo (1.55±0.75). Extended genetic diversity of P. falciparum strains infecting Gabonese symptomatic children and high multiplicity of infections were observed in rural area. Alleles common to the 2 sites were frequent; the site-specific alleles predominated in the rural area. Such distribution of the alleles should be taken into accounts when designing MSP1 or MSP2 malaria vaccine. 相似文献
8.
Vasunun Chumchua Natapol Pornputtapong Chinae Thammarongtham Duangdeun Meksuriyen 《Bioinformation》2008,3(1):18-23
Alpha (α)-enolase (e), a glycolytic enzyme, has an alternative role as a surface receptor of several bacteria mediating plasminogen (pg) binding. It is also recognized as a virulence factor of some pathogenic bacteria facilitating plasminogen activation and host cell invasion. A mycoplasmal α-enolase is also a plasminogen binding protein. Molecular interactions of
enolase from Mycoplasma pneumoniae with host plasminogen would be useful for exploring the pathogen-host interaction. In an attempt to identify plasminogen binding sites of M. pneumoniae enolase, homology modeling and docking studies were conducted to obtain modeled structures of the M. pneumoniae enolase-plasminogen complex. The refined model was validated further
by standard methods. Molecular docking revealed hydrogen bonding of eLys70-pgTyr50, eAsn165-pgThr66, eAla168-pgGlu21, eAsp17-pgLys70, and eAsn213-pgPro68/pgAsn69. Substantial decreases in accessible surface area (ASA) were observed and in concurrence with hydrogen bond pattern. These findings provide a detailed prediction of key residues that interact at the protein-protein interface.
Our theoretical prediction is consistent with known biochemical data. The predicted interaction complex can be of great assistance in understanding structural insights, which is necessary to pathogen and host-component interaction. The ability of M. pneumoniae enolase to bind plasminogen may be indicative of an important role in invasion of this pathogen to host. 相似文献
9.
Pimentel C Choi SJ Chagot B Guette C Camadro JM Darbon H 《Protein science : a publication of the Protein Society》2006,15(3):628-634
Psalmopeotoxin I (PcFK1) is a 33-amino-acid residue peptide isolated from the venom of the tarantula Psalmopoeus cambridgei. It has been recently shown to possess strong antiplasmodial activity against the intra-erythrocyte stage of Plasmodium falciparum in vitro. Although the molecular target for PcFK1 is not yet determined, this peptide does not lyse erythrocytes, is not cytotoxic to nucleated mammalian cells, and does not inhibit neuromuscular function. We investigated the structural properties of PcFK1 to help understand the unique mechanism of action of this peptide and to enhance its utility as a lead compound for rational development of new antimalarial drugs. In this paper, we have determined the three-dimensional solution structure by (1)H two-dimensional NMR means of recombinant PcFK1, which is shown to belong to the ICK structural superfamily with structural determinants common to several neurotoxins acting as ion channels effectors. 相似文献
10.
Most human malaria deaths are caused by blood-stage Plasmodium falciparum parasites. Cerebral malaria, the most life-threatening complication of the disease, is characterised by an accumulation of Plasmodium falciparum infected red blood cells (iRBC) at pigmented trophozoite stage in the microvasculature of the brain(2-4). This microvessel obstruction (sequestration) leads to acidosis, hypoxia and harmful inflammatory cytokines (reviewed in (5)). Sequestration is also found in most microvascular tissues of the human body(2, 3). The mechanism by which iRBC attach to the blood vessel walls is still poorly understood. The immortalized Human Brain microvascular Endothelial Cell line (HBEC-5i) has been used as an in vitro model of the blood-brain barrier(6). However, Plasmodium falciparum iRBC attach only poorly to HBEC-5i in vitro, unlike the dense sequestration that occurs in cerebral malaria cases. We therefore developed a panning assay to select (enrich) various P. falciparum strains for adhesion to HBEC-5i in order to obtain populations of high-binding parasites, more representative of what occurs in vivo. A sample of a parasite culture (mixture of iRBC and uninfected RBC) at the pigmented trophozoite stage is washed and incubated on a layer of HBEC-5i grown on a Petri dish. After incubation, the dish is gently washed free from uRBC and unbound iRBC. Fresh uRBC are added to the few iRBC attached to HBEC-5i and incubated overnight. As schizont stage parasites burst, merozoites reinvade RBC and these ring stage parasites are harvested the following day. Parasites are cultured until enough material is obtained (typically 2 to 4 weeks) and a new round of selection can be performed. Depending on the P. falciparum strain, 4 to 7 rounds of selection are needed in order to get a population where most parasites bind to HBEC-5i. The binding phenotype is progressively lost after a few weeks, indicating a switch in variant surface antigen gene expression, thus regular selection on HBEC-5i is required to maintain the phenotype. In summary, we developed a selection assay rendering P. falciparum parasites a more "cerebral malaria adhesive" phenotype. We were able to select 3 out of 4 P. falciparum strains on HBEC-5i. This assay has also successfully been used to select parasites for binding to human dermal and pulmonary endothelial cells. Importantly, this method can be used to select tissue-specific parasite populations in order to identify candidate parasite ligands for binding to brain endothelium. Moreover, this assay can be used to screen for putative anti-sequestration drugs(7). 相似文献
11.
Polrat Wilairatana Srivicha Krudsood Noppadon Tangpukdee 《The Korean journal of parasitology》2010,48(2):179-182
Artemesinin-combination therapies (ACT) for falciparum malaria reduce gametocyte carriage, and therefore reduce transmission. Artemisinin derivatives will act against only young gametocytes whereas primaquine acts on mature gametocytes which are present usually in the circulation at the time when the patient presents for treatment. Both artemisinin derivatives and primaquine have short half-lives, less than 1 hr and 7 hr, respectively. Therefore, asexual parasites or young gametocytes remain after completed ACT. A single dose of primaquine (0.50-0.75 mg base/kg) at the end of ACT can kill only mature gametocytes but cannot kill young gametocytes (if present). Remaining asexual forms after completion of ACT course, e.g., artesunate-mefloquine for 3 days, may develop to mature gametocytes 7-15 days later. Thus, an additional dose of primaquine (0.50-0.75 mg base/kg) given 2 weeks after ACT completion may be beneficial for killing remaining mature gametocytes and contribute to more interruption of Plasmodium falciparum transmission than giving only 1 single dose of primaquine just after completing ACT. 相似文献
12.
13.
Ji-Xia Ren Cheng-Ping Li Xiu-Ling Zhou Xue-Song Cao Yong Xie 《Journal of biomolecular structure & dynamics》2018,36(9):2424-2435
Myeloid cell leukemia-1 (Mcl-1) has been a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to the resistance to current chemotherapeutics. Here, we identified new Mcl-1 inhibitors using a multi-step virtual screening approach. First, based on two different ligand-receptor complexes, 20 pharmacophore models were established by simultaneously using ‘Receptor-Ligand Pharmacophore Generation’ method and manual build feature method, and then carefully validated by a test database. Then, pharmacophore-based virtual screening (PB-VS) could be performed by using the 20 pharmacophore models. In addition, docking study was used to predict the possible binding poses of compounds, and the docking parameters were optimized before performing docking-based virtual screening (DB-VS). Moreover, a 3D QSAR model was established by applying the 55 aligned Mcl-1 inhibitors. The 55 inhibitors sharing the same scaffold were docked into the Mcl-1 active site before alignment, then the inhibitors with possible binding conformations were aligned. For the training set, the 3D QSAR model gave a correlation coefficient r2 of 0.996; for the test set, the correlation coefficient r2 was 0.812. Therefore, the developed 3D QSAR model was a good model, which could be applied for carrying out 3D QSAR-based virtual screening (QSARD-VS). After the above three virtual screening methods orderly filtering, 23 potential inhibitors with novel scaffolds were identified. Furthermore, we have discussed in detail the mapping results of two potent compounds onto pharmacophore models, 3D QSAR model, and the interactions between the compounds and active site residues. 相似文献
14.
Flaviviruses are small, enveloped RNA viruses which cause a variety of diseases into animals and man. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. A number of studies have already revealed that the non-structural NS3 serine protease is required for the maturation of the viral polyprotein and thus is a promising target for the development of antiviral inhibitors. Hence, the 3D structure of NS3 protein was modeled using homology modeling by MODELLER 9v7. Validation of the constructed NS3 protein models were done by PROCHECK, VERYFY3D and through ProSA calculations. Ligands for the catalytic triad (H51, D75, and S135) were designed using LIGBUILDER. The NS3 protein's catalytic triad was explored to find out the interactions pattern for inhibitor binding using molecular docking methodology using AUTODOCK Vina. The interactions of complex NS3protein-ligand conformations, including hydrogen bonds and the bond lengths were analyzed using Accelrys DS Visualizer software. Hence, from this observation, the novel molecule designed was observed to be the best ligand against the NS3 protein of flavivirus. This molecule may prove to be a potential identity in modulating disease manifestation for all the selected flavivirus members. ABBREVIATIONS: NCBI - National Centre for Biotechnological Information, BLAST - Basic Local Alignment Search Tool, DOPE - Discrete optimized protein energy, GROMOS96 - GROningen MOlecular Simulation package, SAVS - Structure Analysis and Validation Server. 相似文献
15.
Development of new antimalarial drugs continues to be of huge importance because of the resistance of malarial parasite towards currently used drugs. Due to the reliance of parasite on glycolysis for energy generation, glycolytic enzymes have played important role as potential targets for the development of new drugs. Plasmodium falciparum lactate dehydrogenase (PfLDH) is a key enzyme for energy generation of malarial parasites and is considered to be a potential antimalarial target. Presently, there are nearly 15 crystal structures bound with inhibitors and substrate that are available in the protein data bank (PDB). In the present work, we attempted to consider multiple crystal structures with bound inhibitors showing affinity in the range of 1.4 × 102–1.3 × 106 nM efficacy and optimized the pharmacophore based on the energy involved in binding termed as e-pharmacophore mapping. A high throughput virtual screening (HTVS) combined with molecular docking, ADME predictions and molecular dynamics simulation led to the identification of 20 potential compounds which could be further developed as novel inhibitors for PfLDH. 相似文献
16.
Lee HW Moon SU Kim YJ Cho SH Lin K Na BK Kim TS 《The Korean journal of parasitology》2008,46(3):195-198
Plasmodium falciparum liver stage antigen-1 (PfLSA-1) is one of the few antigens expressed exclusively in liver stage parasites. In this study, we evaluated the antibody responses against recombinant PfLSA-1 in naturally infected individuals in Myanmar. High levels of antibody responses (70.7%) were detected in 82 serum samples from 116 infected individuals, and IgG responses to PfLSA-1 principally composed of responses of IgG1 and IgG3 subclasses. These results show that PfLSA-1 elicits effective antibody responses in individuals infected with P. falciparum, and thus it could be not only an attractive candidate protein for vaccine development, but also a useful antigen for serodiagnosis of the infection. 相似文献
17.
Saurabh Pandey Yogesh Kumar Negi Subramanyam Chinreddy Krishnamurthy Sathelly Sandeep Arora Tanushri Kaul 《Bioinformation》2014,10(3):119-123
Ascorbate peroxidase (APX) is a crucial, haeme-containing enzyme of the ascorbate glutathione cycle that detoxifies reactive
oxygen species in plants by catalyzing the conversion of hydrogen peroxide to water using ascorbate as a specific electron donor.
Different APX isoforms are present in discrete subcellular compartments in rice and their expression is stress regulated. We
revealed the homology model of OsAPX1 protein using the crystal structure of soybean GmAPX1 (PDB ID: 2XIF) as template by
Modeller 9.12. The resultant OsAPX1 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that indicated the
model structure is reliable with 83 % amino acid sequence identity with template, RMSD (1.4 Å), Verify3D (86.06 %), Zscores (-8.44)
and Ramachandran plot analysis showed that conformations for 94.6% of amino acid residues are within the most favoured
regions. Investigation revealed two conserved signatures for haeme ligand binding and peroxidase activity in the alpha helical
region that may play a significant role during stress. 相似文献
18.
Lavanya Kakarla Pardhasaradhi Mathi Prasada Rao Allu Chakravarthy Rama Mahendran Botlagunta 《Bioinformation》2014,10(10):637-646
Cyperus scariosus (R.Br) belongs to the family Cyperaceae and it has a diverse medicinal importance. To identify human
cyclooxegenase-2 (COX-2) inhibitors from C. scariosus, the rhizome powder was exhaustively extracted with various solvents based
on the increasing polarity. Based on the presence and absence of secondary metabolites, we have selected the methanolic extract to
evaluate the anti-oxidant and anti-inflammatory activity. The same extract was further subjected to gas chromatography-mass
spectroscopy (GC-MS) analysis to identify the active compounds. Binding affinities of these compounds towards anti-inflammatory
protein COX-2 were analyzed using molecular docking interaction studies. Phytochemical analysis showed that methanol extract is
positive for all secondary metabolites. The antioxidant activity of the C. scariosus rhizomes methanolic extract (CSRME) is half to
that of ascorbic acid at 50 µg/ml. The anti-inflammatory activity of CSRME is higher than that of diclofenac sodium salt at high
concentration, which is evident from the dose dependent inhibition of bovine serum albumin denaturation at 40 µg/ml–5 mg/ml.
GC-MS analysis showed the presence of nine compounds, among all N-methyl-1-adamantaneacetamide and 1,5,diphenyl-2H-1,2,4-
triazine form a hydrogen bond interactions with Ser-530 and Tyr-385 respectively and found similar interactions with crystal
structure of diclofenac bound COX-2 protein. Benzene-1, 2-diol, 4-(4-bromo-3 chlorophenyl iminomethyl forms hydrogen bond
interactions with Thr-199 and Thr-200 as similar to crystallized COX-2 protein with valdecoxib. Collectively our results suggest that
CSRME contains medicinally important anti-inflammatory compounds and this justifies the use of this plant as a folklore medicine
for preventing inflammation associated disorders. 相似文献
19.
Merozoite surface protein-1 (MSP-1) and merozoite surface protein-2 (MSP-2) were used to develop vaccines and to investigate the genetic diversity in Plasmodium falciparum malaria in Iran. Nested polymerase chain reaction amplification was used to determine polymorphisms of block 2 of the MSP-1 and the central domain of MSP-2 genes. A total of 67 microscopically positive P. falciparum infected individuals from a major endemic region, southeast Iran, were included in this trial. Nine alleles of MSP-1 and 11 alleles of MSP-2 were identified. The results showed that amplified product from these surface antigen genes varied in size and there was specific pattern for each isolate. Besides, regarding this pattern, 23 multiple infections with at least 2 alleles were observed. While the endemic regions of malaria in Iran is classified in low to moderate group, but extensive polymorphism was observed for each marker and the MSP-2 central repeat was the most diverse that could be considered in designing malaria vaccine. 相似文献
20.
Judith C. Madden Vera Rogiers Mathieu Vinken 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1656)
There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called ‘adverse outcome pathway’ (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife. 相似文献