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1.
Natochin M Gasimov KG Moussaif M Artemyev NO 《The Journal of biological chemistry》2003,278(39):37574-37581
Three cytoplasmic loops in the G protein-coupled receptor rhodopsin, C2, C3, and C4, have been implicated as key sites for binding and activation of the visual G protein transducin. Non-helical portions of the C2- and C3-loops and the cytoplasmic helix-8 from the C4 loop were targeted for a "gain-of-function" mutagenesis to identify rhodopsin residues critical for transducin activation. Mutant opsins with residues 140-148 (C2-loop), 229-244 (C3-loop), or 310-320 (C4-loop) substituted by poly-Ala sequences of equivalent lengths served as templates for mutagenesis. The template mutants with poly-Ala substitutions in the C2- and C3-loops formed the 500-nm absorbing pigments but failed to activate transducin. Reverse substitutions of the Ala residues by rhodopsin residues have been generated in each of the templates. Significant ( approximately 50%) restoration of the rhodopsin/transducin coupling was achieved with re-introduction of residues Cys140/Lys141 and Arg147/Phe148 into the C2 template. The reverse substitutions of the C3-loop residues Thr229/Val230 and Ser240/Thr242/Thr243/Gln244 produced a pigment with a full capacity for transducin activation. The C4 template mutant was unable to bind 11-cis-retinal, and the presence of Asn310/Lys311 was required for correct folding of the protein. Subsequent mutagenesis of the C4-loop revealed the role of Phe313 and Met317. On the background of Asn310/Lys311, the inclusion of Phe313 and Met317 produced a mutant pigment with the potency of transducin activation equal to that of the wild-type rhodopsin. Overall, our data support the role of the three cytoplasmic loops of rhodopsin and suggest that residues adjacent to the transmembrane helices are most important for transducin activation. 相似文献
2.
Helena J Bailes Wayne L Davies Ann EO Trezise Shaun P Collin 《BMC evolutionary biology》2007,7(1):200
Background
One of the greatest challenges facing the early land vertebrates was the need to effectively interpret a terrestrial environment. Interpretation was based on ocular adaptations evolved for an aquatic environment millions of years earlier. The Australian lungfish Neoceratodus forsteri is thought to be the closest living relative to the first terrestrial vertebrate, and yet nothing is known about the visual pigments present in lungfish or the early tetrapods. 相似文献3.
Proteins containing G-protein regulatory (GPR) motifs represent a novel family of guanine nucleotide dissociation inhibitors (GDIs) for G(alpha) subunits from the Gi family. They selectively interact with the GDP-bound conformation of Gi(alpha) and transducin-alpha (Gt(alpha)), but not with Gs(alpha). A series of chimeric proteins between Gi(alpha)(1) and Gs(alpha) has been constructed to investigate GPR-contact sites on G(alpha) subunits and the mechanism of GPR-protein GDI activity. Analysis of the interaction of two GPR-proteins-AGS3GPR and Pcp2-with the chimeric G(alpha) subunits demonstrated that the GPR-Gi(alpha)(1) interface involves the Gi(alpha)(1) switch regions and Gi(alpha)(1)-144-151, a site within the helical domain. Residues within Gi(alpha)(1)-144-151 form conformation-sensitive contacts with switch III, and may directly interact with a GPR-protein or form a GPR-binding surface jointly with switch III. The helical domain site is critical to the ability of GPR-proteins to act as GDIs. Our data suggest that a mechanism of the GDI activity of GPR-proteins is different from that of GDIs for monomeric GTPases and from the GDI-like activity of G(betagamma) subunits. The GPR-proteins are likely to block a GDP-escape route on G(alpha) subunits. 相似文献
4.
EO Ogueji CD Nwani SC Iheanacho CE Mbah CO Okeke A Yaji 《African Journal of Aquatic Science》2018,43(3):293-303
Indiscriminate discharge of pharmaceutical waste into the aquatic ecosystem may pose serious health challenges to aquatic biota. The effect of acute exposure to ibuprofen was evaluated using changes in behaviour and haematological parameters under static bio-assay method in Clarias gariepinus. Test specimens were exposed to acute concentrations of ibuprofen (0.28, 0.33, 0.38, 0.43 and 0.48 mg l?1) for 24, 48, 72 and 96 h durations respectively. Behavioural and phenotypic changes were observed in surviving fish. There were significant (p < 0.05) concentration and duration-dependent increases in erythrocyte (RBC), haemoglobin (Hb), pack cell volume (PCV) and leukocytes (WBC) in treated fish compared to the control. Insignificant decreases (p > 0.05) in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were observed in treated fish compared to the control. Ibuprofen elicited dose and duration- dependent decrease in neutrophil counts with the decreases being significant (p < 0.05) in the higher doses of 0.43 and 0.48 mg l?1. Ibuprofen did not elicit any significant changes in monocytes, basophils and eosinophils. Changes observed in this study showed that ibuprofen negatively affected the health of the fish and we recommend that discharge of ibuprofen into the aquatic environment should be monitored and controlled. 相似文献
5.
Aliev G Liu J Shenk JC Fischbach K Pacheco GJ Chen SG Obrenovich ME Ward WF Richardson AG Smith MA Gasimov E Perry G Ames BN 《Journal of cellular and molecular medicine》2009,13(2):320-333
Brain function declines with age and is associated with diminishing mitochondrial integrity. The neuronal mitochondrial ultrastructural changes of young (4 months) and old (21 months) F344 rats supplemented with two mitochondrial metabolites, acetyl-L-carnitine (ALCAR, 0.2%[wt/vol] in the drinking water) and R-α-lipoic acid (LA, 0.1%[wt/wt] in the chow), were analysed using qualitative and quantitative electron microscopy techniques. Two independent morphologists blinded to sample identity examined and scored all electron micrographs. Mitochondria were examined in each micrograph, and each structure was scored according to the degree of injury. Controls displayed an age-associated significant decrease in the number of intact mitochondria (P = 0.026) as well as an increase in mitochondria with broken cristae (P < 0.001) in the hippocampus as demonstrated by electron microscopic observations. Neuronal mitochondrial damage was associated with damage in vessel wall cells, especially vascular endothelial cells. Dietary supplementation of young and aged animals increased the proliferation of intact mitochondria and reduced the density of mitochondria associated with vacuoles and lipofuscin. Feeding old rats ALCAR and LA significantly reduced the number of severely damaged mitochondria (P = 0.02) and increased the number of intact mitochondria (P < 0.001) in the hippocampus. These results suggest that feeding ALCAR with LA may ameliorate age-associated mitochondrial ultrastructural decay and are consistent with previous studies showing improved brain function. 相似文献
6.
Gasymov OK Abduragimov AR Gasimov EO Yusifov TN Dooley AN Glasgow BJ 《Biochimica et biophysica acta》2004,1688(2):102-111
The potential of ligand binding proteins as drug carriers and delivery systems has recently sparked great interest. We investigated the potential of tear lipocalin (TL) to bind the antibiotic, rifampin, and the environmental conditions for controlled release. To determine if TL binds rifampin, gel filtration was used to isolate protein fractions of tears. Rifampin was detected by absorbance spectroscopy in the elution fractions containing TL. The bound complex of rifampin-TL generates optical activity at about 360 nm, indicating a unique conformation at the binding site. Rifampin has a higher affinity for TL (Kd=128 microM) than albumin. Rifampin is released from the TL calyx in acidic conditions and is displaced by palmitic acid. Autooxidation of free rifampin begins in minutes but is delayed by at least 3 h in the presence of TL. These properties are conducive to stabilization and delivery of rifampin to tubercles that are acidic and rich in fatty acids. These studies show the potential of TL as a carrier for rifampin with controlled release to a targeted environment. 相似文献
7.
Antonio Montresor David Addiss Marco Albonico Said Mohammed Ali Steven K. Ault Albis-Francesco Gabrielli Amadou Garba Elkhan Gasimov Theresa Gyorkos Mohamed Ahmed Jamsheed Bruno Levecke Pamela Mbabazi Denise Mupfasoni Lorenzo Savioli Jozef Vercruysse Aya Yajima 《PLoS neglected tropical diseases》2015,9(10)
8.
Daniel Engelman Michael Marks Andrew C. Steer Abate Beshah Gautam Biswas Olivier Chosidow Luc E. Coffeng Belen Lardizabal Dofitas Wendemagegn Enbiale Mosoka Fallah Elkhan Gasimov Adrian Hopkins Julie Jacobson John M. Kaldor Fatimata Ly Charles D. Mackenzie Jodie McVernon Matthew Parnaby Merelesita Rainima-Qaniuci Oliver Sokana Dieudonne Sankara Rie Yotsu Aya Yajima Paul T. Cantey 《PLoS neglected tropical diseases》2021,15(9)
Scabies is a neglected tropical disease (NTD) that causes a significant health burden, particularly in disadvantaged communities and where there is overcrowding. There is emerging evidence that ivermectin-based mass drug administration (MDA) can reduce the prevalence of scabies in some settings, but evidence remains limited, and there are no formal guidelines to inform control efforts. An informal World Health Organization (WHO) consultation was organized to find agreement on strategies for global control. The consultation resulted in a framework for scabies control and recommendations for mapping of disease burden, delivery of interventions, and establishing monitoring and evaluation. Key operational research priorities were identified. This framework will allow countries to set control targets for scabies as part of national NTD strategic plans and develop control strategies using MDA for high-prevalence regions and outbreak situations. As further evidence and experience are collected and strategies are refined over time, formal guidelines can be developed. The control of scabies and the reduction of the health burden of scabies and associated conditions will be vital to achieving the targets set in WHO Roadmap for NTDs for 2021 to 2030 and the Sustainable Development Goals. 相似文献
9.
Nargiz J. Agayeva Fuad H. Rzayev Eldar K. Gasimov Chingiz A. Mamedov Ismat S. Ahmadov Narmina A. Sadigova Ameer Khusro Naif Abdullah Al-Dhabi Mariadhas Valan Arasu 《Saudi Journal of Biological Sciences》2020,27(12):3258-3266
The widespread exposure of metallic nanoparticles to the aquatic ecosystem and its adverse impact on human life is the colossal concern worldwide. In view of this, this context was investigated to analyze microscopically the bioaccumulation and localization of magnetite (Fe3O4) nanoparticles in the cellular organelles of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) in aquatic conditions. Initially, Fe3O4 nanoparticles were absorbed on to Elodea (Elodea canadensis) and fed to molluscs (Melanopsis praemorsa). Fish were fed with the same molluscs, and then the intestines and liver were examined using light and transmission electron microscopy. Results showed that nanoparticles were present in the cytoplasm and other organelles of cells (mitochondrion and lysosome) by absorbing through microvilli of the epithelial cells of the tunica mucosa in the intestine. Further, nanoparticles passed through the vessels of the lamina propria of the tunica mucosa and reached to the sinusoids of the liver via blood circulation. It was then accumulated from the endothelium of the sinusoid to the cytoplasm of liver hepatocytes and to mitochondria and lysosome. The accumulation of nanoparticles in the epithelial cells, cytoplasm, mitochondria, and lysosome revealed the degree of transparency of the pattern with slight hesitation. In summary, this investigation contributed towards the understanding of the physiological effects of Fe3O4 nanoparticles on O. mykiss, which ascertains essentiality for sustainable development of nanobiotechnology in the aquatic ecosystem. 相似文献
10.
BRANT C. FAIRCLOTH ALLISON REID TERESA VALENTINE SOO HYUNG EO THERON M. TERHUNE TRAVIS C. GLENN WILLIAM E. PALMER CAMPBELL JOSEPH NAIRN JOHN P. CARROLL 《Molecular ecology resources》2005,5(2):387-389
We describe primers and polymerase chain reaction (PCR) conditions to amplify four dinucleotide, one trinucleotide, and three tetranucleotide microsatellite DNA loci from the bobcat (Lynx rufus). The primers were tested on 22 individuals collected from a population located within southwestern Georgia (USA). The primer pairs developed in this study yielded an average of 7.4 alleles per locus (range four to 10), an average observed heterozygosity of 0.60 (range 0.40 to 0.76), and an average polymorphic information content of 0.70 (range 0.51 to 0.78). 相似文献