Albendazole is a benzimidazole derivative with broad spectrum anthelmenthic activity and excellen... more Albendazole is a benzimidazole derivative with broad spectrum anthelmenthic activity and excellent tolerability. Orally it is rapidly absorbed and metabolized to sulfoxide and sulfone, which may be responsible for its anthelmenthic action. Single dose administration of albendazole has produced cure rates in ascarisis, hookworm and enterobiasis which are comparable to three day treatment with mebendazole. Albendazole chewable tablets (400 mg) were prepared by three methods viz. non aqueous granulation, aqueous granulation and direct compression and were named as NAG, AG and DC respectively. Tablet prepared by these three methods were evaluated by different parameters such as average weight, hardness, carr's index, tapped density, friability, disintegration, content uniformity test, in vitro dissolution etc. All the parameters were found within the specifications. The study on the dissolution profile revealed that product 'DC' had faster dissolution rate while compared to ...
International Journal of Computer Applications, 2013
The applications of emotion recognition in consumer electronics are increasing day by day. Howeve... more The applications of emotion recognition in consumer electronics are increasing day by day. However the accuracy and stability of the decisions made by appliances largely depends on the efficient recognition of these emotions. The performance may degrade drastically due to interfering noise. This paper proposes a method which may improve the accuracy significantly. Results have confirmed that this system may help to improve the recognition results.
During formation of the Hedgehog (Hh) signaling proteins, cooperative activities of the Hedgehog ... more During formation of the Hedgehog (Hh) signaling proteins, cooperative activities of the Hedgehog INTein (Hint) fold and Sterol Recognition Region (SRR) couple autoproteolysis to cholesterol ligation. The cholesteroylated Hh morphogens play essential roles in embryogenesis, tissue regeneration, and tumorigenesis. Despite the centrality of cholesterol in Hh function, the full structure of the Hint-SRR (“Hog”) domain that attaches cholesterol to the last residue of the active Hh morphogen remains enigmatic. In this work, we combine molecular dynamics simulations, photoaffinity crosslinking, and mutagenesis assays to model cholesterolysis intermediates in the human Sonic Hedgehog (hSHH) protein. Our results provide evidence for a hydrophobic Hint-SRR interface that forms a dynamic, non-covalent cholesterol-Hog complex. Using these models, we suggest a unified mechanism by which Hh proteins can recruit, sequester, and orient cholesterol, and offer a molecular basis for the effects of dis...
Nature provides a number of mechanisms to encode dynamic information in biomolecules. In metazoan... more Nature provides a number of mechanisms to encode dynamic information in biomolecules. In metazoans, there exist rare chemical modifications that occur through entirely unique mechanistic regimes. One such example occurs in the Hedgehog (Hh) morphogens, proteins singular across all domains of life for the nature of their covalent ligation to cholesterol. The isoform- and context-specific efficiency of the ligation reaction has profound impact on the activity of Hh morphogens and represents an unexplored aspect of Hh ligand-dependent cancers. To elucidate the chemical mechanism of this modification, we have defined roles of the uncharacterized sterol recognition region (SRR) in Hh proteins. We use a combination of sequence conservation, directed mutagenesis, and biochemical assays to specify residues of the SRR that are responsible for cellular and biochemical processes in Hh cholesterolysis. Our investigations offer the first functional template of this region, providing opportunitie...
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Aerobic methane oxidation is catalyzed by particulate methane monooxygenase (pMMO), a copper-depe... more Aerobic methane oxidation is catalyzed by particulate methane monooxygenase (pMMO), a copper-dependent, membrane metalloenzyme composed of subunits PmoA, PmoB, and PmoC. Characterization of the copper active site has been limited by challenges in spectroscopic analysis stemming from the presence of multiple copper binding sites, effects of detergent solubilization on activity and crystal structures, and the lack of a heterologous expression system. Here we utilize nanodiscs coupled with native top-down mass spectrometry (nTDMS) to determine the copper stoichiometry in each pMMO subunit and to detect post-translational modifications (PTMs). These results indicate the presence of a mononuclear copper center in both PmoB and PmoC. pMMO-nanodisc complexes with a higher stoichiometry of copper-bound PmoC exhibit increased activity, suggesting that the PmoC copper site plays a role in methane oxidation activity. These results provide key insights into the pMMO copper centers and demonstrate the ability of nTDMS to characterize complex membrane-bound metalloenzymes.
Proceedings of the National Academy of Sciences of the United States of America, Feb 27, 2018
The copper-transporting P-ATPases, which play a key role in cellular copper homeostasis, have bee... more The copper-transporting P-ATPases, which play a key role in cellular copper homeostasis, have been divided traditionally into two subfamilies, the P-ATPases or CopAs and the P-ATPases or CopBs. CopAs selectively export Cu whereas previous studies and bioinformatic analyses have suggested that CopBs are specific for Cu export. Biochemical and spectroscopic characterization of CopB (CopB) show that, while it does bind Cu, the binding site is not the prototypical P-ATPase transmembrane site and does not involve sulfur coordination as proposed previously. Most important, CopB exhibits metal-stimulated ATPase activity in response to Cu, but not Cu, indicating that it is actually a Cu transporter. X-ray absorption spectroscopic studies indicate that Cu is coordinated by four sulfur ligands, likely derived from conserved cysteine and methionine residues. The histidine-rich N-terminal region of CopB is required for maximal activity, but is inhibitory in the presence of divalent metal ions. ...
Well-known surface properties of gold nanoparticles (AuNPs) offer easy surface modification with ... more Well-known surface properties of gold nanoparticles (AuNPs) offer easy surface modification with desired biomolecule, thus enabling them to be used for targeting and imaging of cancer cells/tissues. However, targeting and imaging capability come through after synthesis coating of AuNPs' surface with targeting or imaging molecules. Attempts have been made to conjugate both imaging and targeting molecules over the AuNPs, but have seen limited success. Hence, exploiting the fluorescence properties of gold nanoclusters (AuNCs), we have synthesized glucose-coated AuNCs for exhibiting both the imaging and targeting properties. These clusters have shown rapid and selective uptake in cancerous (A549) cells when compared with bovine serum albumin-coated AuNCs.
Road traffic accidents (RTA) are one of the major root causes of the unnatural loses of human bei... more Road traffic accidents (RTA) are one of the major root causes of the unnatural loses of human beings all over the world. Although the rates of RTAs are decreasing in most developed countries, this is not the case in developing countries. The increase in the number of vehicles and inefficient drivers on the road, as well as to the poor conditions and maintenance of the roads, are responsible for this crisis in developing countries. In this paper, we produce a design of an Artificial Neural Network (ANN) model for the analysis and prediction of accident rates in a developing country. We apply the most recent (1998 to 2010) data to our model. In the design, the number of vehicles, accidents, and population were selected and used as model parameters. The sigmoid and linear functions were used as activation functions with the feed forward-back propagation algorithm. The F. N. Ogwueleka et al. An Artificial Neural Network Model for Road Accident Prediction: A Case Study of a Developing Country-178-performance evaluation of the model signified that the ANN model is better than other statistical methods in use.
Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has shown a wide sp... more Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has shown a wide spectrum of biological actions. Clinically, curcumin has already been used to reduce post-operative inflammation. Safety evaluation studies indicate that curcumin is well tolerated at a very high dose without any toxic effects. Moreover, curcumin have the potential for the development of modern medicine for the treatment of various diseases. This review paper serves to highlight the extensive work done to establish the biological and pharmacological actions, safety and stability aspects along with the structure and possible modifications in curcumin to enhance its bioeffectiveness.
The term "liquisolid medication" implies oily liquid drugs and solutions or suspensions of water ... more The term "liquisolid medication" implies oily liquid drugs and solutions or suspensions of water insoluble drugs carried in suitable non-volatile solvent systems. Liquisolid compacts demonstrated a considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets. This was due to the increased wetting properties and surface of drug available for dissolution. This review paper highlights the application of liquisolid technique to enhance the solubility and dissolution of water insoluble drugs. This technique is appropriate for poorly or water insoluble drugs and also for immediate or sustained release formulations. This review also depicts the various formulation parameters that must be optimized before formulation the liquisolid compacts.
For the first time, we report a facile strategy for the synthesis of ultra-fine blue-green emitti... more For the first time, we report a facile strategy for the synthesis of ultra-fine blue-green emitting fluorescent magnesium nanoparticles–protein complex (MgNC) which shows excellent photo stability and also stain cell nuclei with high specificity.
Gold nanoparticles (AuNPs) are known to possess intrinsic biological peroxidase-like activity tha... more Gold nanoparticles (AuNPs) are known to possess intrinsic biological peroxidase-like activity that has applications in development of numerous biosensors. The reactivity of the Au atoms at the surface of AuNPs is critical to the performance of such biosensors, yet little is known about the effect of biomolecules and ions on the peroxidase-like activity. In this work, the effect of ATP and other biologically relevant molecules and ions over peroxidase-like activity of AuNPs are described. Contrary to the expectation that nanoparticles exposed to biomolecules may lose the catalytic property, ATP and ADP addition enhanced the peroxidase-like activity of AuNPs. The catalytic activity was unaltered by the addition of free phosphate, sulphate and carbonate anions however, addition of ascorbic acid to the reaction mixture diminished the intrinsic peroxidase-like activity of AuNPs, even in the presence of ATP and ADP. In contrast to AuNPs, ATP did not synergize and improve the peroxidase activity of the natural peroxidase enzyme, horseradish peroxidase.
A family of enediyne-estrogens has been prepared, and evaluated for affinity to hER. The optimal ... more A family of enediyne-estrogens has been prepared, and evaluated for affinity to hER. The optimal ligand has nM affinity, and undergoes photoBergman cycloaromatization.
Soluble guanylate cyclase (sGC) is a heterodimeric heme protein of ≈ 150 kDa and the primary nitr... more Soluble guanylate cyclase (sGC) is a heterodimeric heme protein of ≈ 150 kDa and the primary nitric oxide receptor. Binding of NO stimulates cyclase activity, leading to regulation of cardiovascular physiology and providing attractive opportunities for drug discovery. How sGC is stimulated and where candidate drugs bind remains unknown. The α and β sGC chains are each composed of Heme-Nitric Oxide Oxygen (H-NOX), Per-ARNT-Sim (PAS), coiled-coil and cyclase domains. Here, we present the crystal structure of the α1 PAS domain to 1.8 Å resolution. The structure reveals the binding surfaces of importance to heterodimer function, particularly with respect to regulating NO binding to heme in the β1 H-NOX domain. It also reveals a small internal cavity that may serve to bind ligands or participate in signal transduction.
Albendazole is a benzimidazole derivative with broad spectrum anthelmenthic activity and excellen... more Albendazole is a benzimidazole derivative with broad spectrum anthelmenthic activity and excellent tolerability. Orally it is rapidly absorbed and metabolized to sulfoxide and sulfone, which may be responsible for its anthelmenthic action. Single dose administration of albendazole has produced cure rates in ascarisis, hookworm and enterobiasis which are comparable to three day treatment with mebendazole. Albendazole chewable tablets (400 mg) were prepared by three methods viz. non aqueous granulation, aqueous granulation and direct compression and were named as NAG, AG and DC respectively. Tablet prepared by these three methods were evaluated by different parameters such as average weight, hardness, carr's index, tapped density, friability, disintegration, content uniformity test, in vitro dissolution etc. All the parameters were found within the specifications. The study on the dissolution profile revealed that product 'DC' had faster dissolution rate while compared to ...
International Journal of Computer Applications, 2013
The applications of emotion recognition in consumer electronics are increasing day by day. Howeve... more The applications of emotion recognition in consumer electronics are increasing day by day. However the accuracy and stability of the decisions made by appliances largely depends on the efficient recognition of these emotions. The performance may degrade drastically due to interfering noise. This paper proposes a method which may improve the accuracy significantly. Results have confirmed that this system may help to improve the recognition results.
During formation of the Hedgehog (Hh) signaling proteins, cooperative activities of the Hedgehog ... more During formation of the Hedgehog (Hh) signaling proteins, cooperative activities of the Hedgehog INTein (Hint) fold and Sterol Recognition Region (SRR) couple autoproteolysis to cholesterol ligation. The cholesteroylated Hh morphogens play essential roles in embryogenesis, tissue regeneration, and tumorigenesis. Despite the centrality of cholesterol in Hh function, the full structure of the Hint-SRR (“Hog”) domain that attaches cholesterol to the last residue of the active Hh morphogen remains enigmatic. In this work, we combine molecular dynamics simulations, photoaffinity crosslinking, and mutagenesis assays to model cholesterolysis intermediates in the human Sonic Hedgehog (hSHH) protein. Our results provide evidence for a hydrophobic Hint-SRR interface that forms a dynamic, non-covalent cholesterol-Hog complex. Using these models, we suggest a unified mechanism by which Hh proteins can recruit, sequester, and orient cholesterol, and offer a molecular basis for the effects of dis...
Nature provides a number of mechanisms to encode dynamic information in biomolecules. In metazoan... more Nature provides a number of mechanisms to encode dynamic information in biomolecules. In metazoans, there exist rare chemical modifications that occur through entirely unique mechanistic regimes. One such example occurs in the Hedgehog (Hh) morphogens, proteins singular across all domains of life for the nature of their covalent ligation to cholesterol. The isoform- and context-specific efficiency of the ligation reaction has profound impact on the activity of Hh morphogens and represents an unexplored aspect of Hh ligand-dependent cancers. To elucidate the chemical mechanism of this modification, we have defined roles of the uncharacterized sterol recognition region (SRR) in Hh proteins. We use a combination of sequence conservation, directed mutagenesis, and biochemical assays to specify residues of the SRR that are responsible for cellular and biochemical processes in Hh cholesterolysis. Our investigations offer the first functional template of this region, providing opportunitie...
An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Aerobic methane oxidation is catalyzed by particulate methane monooxygenase (pMMO), a copper-depe... more Aerobic methane oxidation is catalyzed by particulate methane monooxygenase (pMMO), a copper-dependent, membrane metalloenzyme composed of subunits PmoA, PmoB, and PmoC. Characterization of the copper active site has been limited by challenges in spectroscopic analysis stemming from the presence of multiple copper binding sites, effects of detergent solubilization on activity and crystal structures, and the lack of a heterologous expression system. Here we utilize nanodiscs coupled with native top-down mass spectrometry (nTDMS) to determine the copper stoichiometry in each pMMO subunit and to detect post-translational modifications (PTMs). These results indicate the presence of a mononuclear copper center in both PmoB and PmoC. pMMO-nanodisc complexes with a higher stoichiometry of copper-bound PmoC exhibit increased activity, suggesting that the PmoC copper site plays a role in methane oxidation activity. These results provide key insights into the pMMO copper centers and demonstrate the ability of nTDMS to characterize complex membrane-bound metalloenzymes.
Proceedings of the National Academy of Sciences of the United States of America, Feb 27, 2018
The copper-transporting P-ATPases, which play a key role in cellular copper homeostasis, have bee... more The copper-transporting P-ATPases, which play a key role in cellular copper homeostasis, have been divided traditionally into two subfamilies, the P-ATPases or CopAs and the P-ATPases or CopBs. CopAs selectively export Cu whereas previous studies and bioinformatic analyses have suggested that CopBs are specific for Cu export. Biochemical and spectroscopic characterization of CopB (CopB) show that, while it does bind Cu, the binding site is not the prototypical P-ATPase transmembrane site and does not involve sulfur coordination as proposed previously. Most important, CopB exhibits metal-stimulated ATPase activity in response to Cu, but not Cu, indicating that it is actually a Cu transporter. X-ray absorption spectroscopic studies indicate that Cu is coordinated by four sulfur ligands, likely derived from conserved cysteine and methionine residues. The histidine-rich N-terminal region of CopB is required for maximal activity, but is inhibitory in the presence of divalent metal ions. ...
Well-known surface properties of gold nanoparticles (AuNPs) offer easy surface modification with ... more Well-known surface properties of gold nanoparticles (AuNPs) offer easy surface modification with desired biomolecule, thus enabling them to be used for targeting and imaging of cancer cells/tissues. However, targeting and imaging capability come through after synthesis coating of AuNPs' surface with targeting or imaging molecules. Attempts have been made to conjugate both imaging and targeting molecules over the AuNPs, but have seen limited success. Hence, exploiting the fluorescence properties of gold nanoclusters (AuNCs), we have synthesized glucose-coated AuNCs for exhibiting both the imaging and targeting properties. These clusters have shown rapid and selective uptake in cancerous (A549) cells when compared with bovine serum albumin-coated AuNCs.
Road traffic accidents (RTA) are one of the major root causes of the unnatural loses of human bei... more Road traffic accidents (RTA) are one of the major root causes of the unnatural loses of human beings all over the world. Although the rates of RTAs are decreasing in most developed countries, this is not the case in developing countries. The increase in the number of vehicles and inefficient drivers on the road, as well as to the poor conditions and maintenance of the roads, are responsible for this crisis in developing countries. In this paper, we produce a design of an Artificial Neural Network (ANN) model for the analysis and prediction of accident rates in a developing country. We apply the most recent (1998 to 2010) data to our model. In the design, the number of vehicles, accidents, and population were selected and used as model parameters. The sigmoid and linear functions were used as activation functions with the feed forward-back propagation algorithm. The F. N. Ogwueleka et al. An Artificial Neural Network Model for Road Accident Prediction: A Case Study of a Developing Country-178-performance evaluation of the model signified that the ANN model is better than other statistical methods in use.
Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has shown a wide sp... more Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has shown a wide spectrum of biological actions. Clinically, curcumin has already been used to reduce post-operative inflammation. Safety evaluation studies indicate that curcumin is well tolerated at a very high dose without any toxic effects. Moreover, curcumin have the potential for the development of modern medicine for the treatment of various diseases. This review paper serves to highlight the extensive work done to establish the biological and pharmacological actions, safety and stability aspects along with the structure and possible modifications in curcumin to enhance its bioeffectiveness.
The term "liquisolid medication" implies oily liquid drugs and solutions or suspensions of water ... more The term "liquisolid medication" implies oily liquid drugs and solutions or suspensions of water insoluble drugs carried in suitable non-volatile solvent systems. Liquisolid compacts demonstrated a considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets. This was due to the increased wetting properties and surface of drug available for dissolution. This review paper highlights the application of liquisolid technique to enhance the solubility and dissolution of water insoluble drugs. This technique is appropriate for poorly or water insoluble drugs and also for immediate or sustained release formulations. This review also depicts the various formulation parameters that must be optimized before formulation the liquisolid compacts.
For the first time, we report a facile strategy for the synthesis of ultra-fine blue-green emitti... more For the first time, we report a facile strategy for the synthesis of ultra-fine blue-green emitting fluorescent magnesium nanoparticles–protein complex (MgNC) which shows excellent photo stability and also stain cell nuclei with high specificity.
Gold nanoparticles (AuNPs) are known to possess intrinsic biological peroxidase-like activity tha... more Gold nanoparticles (AuNPs) are known to possess intrinsic biological peroxidase-like activity that has applications in development of numerous biosensors. The reactivity of the Au atoms at the surface of AuNPs is critical to the performance of such biosensors, yet little is known about the effect of biomolecules and ions on the peroxidase-like activity. In this work, the effect of ATP and other biologically relevant molecules and ions over peroxidase-like activity of AuNPs are described. Contrary to the expectation that nanoparticles exposed to biomolecules may lose the catalytic property, ATP and ADP addition enhanced the peroxidase-like activity of AuNPs. The catalytic activity was unaltered by the addition of free phosphate, sulphate and carbonate anions however, addition of ascorbic acid to the reaction mixture diminished the intrinsic peroxidase-like activity of AuNPs, even in the presence of ATP and ADP. In contrast to AuNPs, ATP did not synergize and improve the peroxidase activity of the natural peroxidase enzyme, horseradish peroxidase.
A family of enediyne-estrogens has been prepared, and evaluated for affinity to hER. The optimal ... more A family of enediyne-estrogens has been prepared, and evaluated for affinity to hER. The optimal ligand has nM affinity, and undergoes photoBergman cycloaromatization.
Soluble guanylate cyclase (sGC) is a heterodimeric heme protein of ≈ 150 kDa and the primary nitr... more Soluble guanylate cyclase (sGC) is a heterodimeric heme protein of ≈ 150 kDa and the primary nitric oxide receptor. Binding of NO stimulates cyclase activity, leading to regulation of cardiovascular physiology and providing attractive opportunities for drug discovery. How sGC is stimulated and where candidate drugs bind remains unknown. The α and β sGC chains are each composed of Heme-Nitric Oxide Oxygen (H-NOX), Per-ARNT-Sim (PAS), coiled-coil and cyclase domains. Here, we present the crystal structure of the α1 PAS domain to 1.8 Å resolution. The structure reveals the binding surfaces of importance to heterodimer function, particularly with respect to regulating NO binding to heme in the β1 H-NOX domain. It also reveals a small internal cavity that may serve to bind ligands or participate in signal transduction.
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Papers by Rahul Purohit