Enzymes in Degradation of the Lignocellulosic Wastes, 2020
Lipases enzyme are very important in the degradation of lignocellulosic wastes. The chapter here ... more Lipases enzyme are very important in the degradation of lignocellulosic wastes. The chapter here describes in detail the structure of lipase; classification of lipase enzyme including bacterial lipases; and reactions catalyzed by lipase enzyme. The chapter also focuses on active and catalytic residues of lipase enzyme; the catalytic mechanism of lipases; lipase-producing bacteria and fungi; and assays for lipase enzyme activity and applications of lipases enzyme. The chapter gives detailed information on lipase enzyme in degradation of lignocellulose wastes. This will help in the proper management of lignocellulosic waste.
Background In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio (CFR) ... more Background In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio (CFR) and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-November. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. Methodology We state six testable alternative hypotheses, analyze their testable predictions using public domain data and evaluate their relative contributions to the downward trend. Results We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including ...
Pectin is one of the major plant cell wall components. Degradation of pectin is difficult, and pe... more Pectin is one of the major plant cell wall components. Degradation of pectin is difficult, and pectinases enzyme can help in the degradation of pectin. The chapter described here mentions the pectic substances, viz. protopectin, pectinic acids, pectin or pectins, and pectic acids. The mechanism of action of the pectinolytic enzymes is also described along with the occurrence of pectinolytic enzymes. The physiochemical and biological properties of pectinases enzyme is also focused. The assay methods of pectinolytic enzymes and the production of pectinase enzymes by bacteria and fungi using fermentation are also described. The various applications of pectinases in the deconstruction of lignocellulosic wastes are also taken into consideration. This will help in understanding pectinolytic enzymes and their mechanisms of action which give insights on the role of pectinases in the degradation of lignocellulosic wastes.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this p... more The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Among the classical models of optimization, some models maximize the ratio of returns per investm... more Among the classical models of optimization, some models maximize the ratio of returns per investment, others maximize the difference between returns and investment. However, the question under what conditions use of the ratio model is appropriate and under what conditions a difference model should be used remained unaddressed until recently. The question is important because the strategies indicated by ratio optimum can be substantially different than the ones suggested by difference optimum. We make a general case here for the set of conditions for appropriate use of ratio versus difference optimum. When the investable amount is perceived as limiting but not the investment opportunities a ratio optimum is appropriate and when the investment opportunities are perceived to be limiting but not the investable amount, difference optimum is appropriate. Taking examples of Concorde fallacy, parental investment, r and K selection, nectar production, pollinator behavior, protein synthesis a...
Among the classical models of optimization, some models maximize the ratio of returns per investm... more Among the classical models of optimization, some models maximize the ratio of returns per investment, others maximize the difference between returns and investment. However, the question under what conditions use of the ratio model is appropriate and under what conditions a difference model should be used remained unaddressed until recently. The question is important because the strategies indicated by ratio optimum can be substantially different than the ones suggested by difference optimum. We make a general case here for the set of conditions for appropriate use of ratio versus difference optimum. When the investable amount is perceived as limiting but not the investment opportunities a ratio optimum is appropriate and when the investment opportunities are perceived to be limiting but not the investable amount, difference optimum is appropriate. Taking examples of Concorde fallacy, parental investment, r and K selection, nectar production, pollinator behavior, protein synthesis a...
In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices... more In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, i...
In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices... more In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, i...
High throughput technologies have characterized a multitude of genes involved in different cellul... more High throughput technologies have characterized a multitude of genes involved in different cellular process. These are controlled by complex regulatory mechanism involving the gene products, forming an intricate gene regulatory network. A unified systems approach is needed to understand the dynamics of such an intriguing network. Many different approaches have been used to model and simulate the gene regulatory networks. This chapter discusses in brief the basic concept involved in Bayesian and Boolean approaches for studying the gene regulatory network, citing examples from recent work in this area of computational biology.
High throughput technologies have characterized a multitude of genes involved in different cellul... more High throughput technologies have characterized a multitude of genes involved in different cellular process. These are controlled by complex regulatory mechanism involving the gene products, forming an intricate gene regulatory network. A unified systems approach is needed to understand the dynamics of such an intriguing network. Many different approaches have been used to model and simulate the gene regulatory networks. This chapter discusses in brief the basic concept involved in Bayesian and Boolean approaches for studying the gene regulatory network, citing examples from recent work in this area of computational biology.
Selection pressure governs the relative mutability and the conservedness of a protein across the ... more Selection pressure governs the relative mutability and the conservedness of a protein across the protein family. Biomolecules (DNA, RNA and proteins) continuously evolve under the effect of evolutionary pressure that arises as a consequence of the host parasite interaction. IPCS (Inositol phosphorylceramide synthase), SPL (Sphingosine-1-P lyase) and SPT (Serine palmitoyl transferase) represent three important enzymes involved in the sphingolipid metabolism of Leishmania. These enzymes are responsible for maintaining the viability and infectivity of the parasite and have been classified as druggable targets in the parasite metabolome. The present work relates to the role of selection pressure deciding functional conservedness and divergence of the drug targets. IPCS and SPL protein families appear to diverge from the SPT family. The three protein families were largely under the influence of purifying selection and were moderately conserved baring two residues in the IPCS protein whic...
Leishmania major causes cutaneous form of Leishmaniasis affecting 21 million people in developing... more Leishmania major causes cutaneous form of Leishmaniasis affecting 21 million people in developing countries. Overuse of the chemotherapeutics against leishmaniasis has resulted in the development of drug resistance in the parasite. To surmount this emerging threat we have attempted to target the surface molecules. Glycosylphosphatidylinositol is one such molecule that is present abundantly and thus our work revolves around the enzyme mannosyltransferase (GPI 14), an enzyme essential to add mannose on the glycosylphosphatidyl. It has been targeted for drug discovery on account of growing resistance to miltefosine in L. major. This paper serves as the first attempt to detect GPI 14 gene in L. major supported with modeling and molecular dynamic analysis of complete three dimensional structure of GPI 14. The functional analysis revealed multiple transmembrane regions in GPI 14 and a close phylogenetic relation with Trypanosoma species and Schistosoma mansoni with highest bootstrap value...
Background: Selection pressure governs the relative mutability and the conservedness of a protein... more Background: Selection pressure governs the relative mutability and the conservedness of a protein across the protein family. Biomolecules (DNA, RNA and proteins) continuously evolve under the effect of evolutionary pressure that arises as a consequence of the host parasite interaction. IPCS (Inositol phosphorylceramide synthase), SPL (Sphingosine-1-P lyase) and SPT (Serine palmitoyl transferase) represent three important enzymes involved in the sphingolipid metabolism of Leishmania. These enzymes are responsible for maintaining the viability and infectivity of the parasite and have been classified as druggable targets in the parasite metabolome. Results: The present work relates to the role of selection pressure deciding functional conservedness and divergence of the drug targets. IPCS and SPL protein families appear to diverge from the SPT family. The three protein families were largely under the influence of purifying selection and were moderately conserved baring two residues in the IPCS protein which were under the influence of positive selection. To further explore the selection pressure at the codon level, codon usage bias indices were calculated to analyze genes for their synonymous codon usage pattern. IPCS gene exhibited slightly lower codon bias as compared to SPL and SPT protein families. Conclusion: Evolutionary tracing of the proposed drug targets has been done with a viewpoint that the amino-acids lining the drug binding pocket should have a lower evolvability. Sites under positive selection (HIS20 and CYS30 of IPCS) should be avoided during devising strategies for inhibitor design.
Understanding network topology through embracing the global dynamical regulation of genes in an a... more Understanding network topology through embracing the global dynamical regulation of genes in an active state space rather than traditional one-gene-one trait approach facilitates the rational drug development process. Schistosomiasis, a neglected tropical disease, has glycerophospholipids as abundant molecules present on its surface. Lack of effective clinical solutions to treat pathogens encourages us to carry out systems-level studies that could contribute to the development of an effective therapy. Development of a strategy for identifying drug targets by combined genome-scale metabolic network and essentiality analyses through in silico approaches provides tantalizing opportunity to investigate the role of protein/substrate metabolism. A genome-scale metabolic network model reconstruction represents choline-phosphate cytidyltransferase as the rate limiting enzyme and regulates the rate of phosphatidylcholine (PC) biosynthesis. The uptake of choline was regulated by choline concentration, promoting the regulation of phosphocholine synthesis. In Schistosoma, the change in developmental stage could result from the availability of choline, hampering its developmental cycle. There are no structural reports for this protein. In order to inhibit the activity of choline-phosphate cytidyltransferase (CCT), it was modeled by homology modeling using 1COZ as the template from Bacillus subtilis. The transition-state stabilization and catalytic residues were mapped as 'HXGH' and 'RTEGISTT' motif. CCT catalyzes the formation of CDP-choline from phosphocholine in which nucleotidyltransferase adds CTP to phosphocholine. The presence of phosphocholine permits the parasite to survive in an immunologically hostile environment. This feature endeavors development of an inhibitor specific for cytidyltransferase in Schistosoma. Flavonolignans were used to inhibit this activity in which hydnowightin showed the highest affinity as compared to miltefosine.
Enzymes in Degradation of the Lignocellulosic Wastes, 2020
Lipases enzyme are very important in the degradation of lignocellulosic wastes. The chapter here ... more Lipases enzyme are very important in the degradation of lignocellulosic wastes. The chapter here describes in detail the structure of lipase; classification of lipase enzyme including bacterial lipases; and reactions catalyzed by lipase enzyme. The chapter also focuses on active and catalytic residues of lipase enzyme; the catalytic mechanism of lipases; lipase-producing bacteria and fungi; and assays for lipase enzyme activity and applications of lipases enzyme. The chapter gives detailed information on lipase enzyme in degradation of lignocellulose wastes. This will help in the proper management of lignocellulosic waste.
Background In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio (CFR) ... more Background In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio (CFR) and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-November. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. Methodology We state six testable alternative hypotheses, analyze their testable predictions using public domain data and evaluate their relative contributions to the downward trend. Results We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including ...
Pectin is one of the major plant cell wall components. Degradation of pectin is difficult, and pe... more Pectin is one of the major plant cell wall components. Degradation of pectin is difficult, and pectinases enzyme can help in the degradation of pectin. The chapter described here mentions the pectic substances, viz. protopectin, pectinic acids, pectin or pectins, and pectic acids. The mechanism of action of the pectinolytic enzymes is also described along with the occurrence of pectinolytic enzymes. The physiochemical and biological properties of pectinases enzyme is also focused. The assay methods of pectinolytic enzymes and the production of pectinase enzymes by bacteria and fungi using fermentation are also described. The various applications of pectinases in the deconstruction of lignocellulosic wastes are also taken into consideration. This will help in understanding pectinolytic enzymes and their mechanisms of action which give insights on the role of pectinases in the degradation of lignocellulosic wastes.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this p... more The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Among the classical models of optimization, some models maximize the ratio of returns per investm... more Among the classical models of optimization, some models maximize the ratio of returns per investment, others maximize the difference between returns and investment. However, the question under what conditions use of the ratio model is appropriate and under what conditions a difference model should be used remained unaddressed until recently. The question is important because the strategies indicated by ratio optimum can be substantially different than the ones suggested by difference optimum. We make a general case here for the set of conditions for appropriate use of ratio versus difference optimum. When the investable amount is perceived as limiting but not the investment opportunities a ratio optimum is appropriate and when the investment opportunities are perceived to be limiting but not the investable amount, difference optimum is appropriate. Taking examples of Concorde fallacy, parental investment, r and K selection, nectar production, pollinator behavior, protein synthesis a...
Among the classical models of optimization, some models maximize the ratio of returns per investm... more Among the classical models of optimization, some models maximize the ratio of returns per investment, others maximize the difference between returns and investment. However, the question under what conditions use of the ratio model is appropriate and under what conditions a difference model should be used remained unaddressed until recently. The question is important because the strategies indicated by ratio optimum can be substantially different than the ones suggested by difference optimum. We make a general case here for the set of conditions for appropriate use of ratio versus difference optimum. When the investable amount is perceived as limiting but not the investment opportunities a ratio optimum is appropriate and when the investment opportunities are perceived to be limiting but not the investable amount, difference optimum is appropriate. Taking examples of Concorde fallacy, parental investment, r and K selection, nectar production, pollinator behavior, protein synthesis a...
In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices... more In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, i...
In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices... more In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, i...
High throughput technologies have characterized a multitude of genes involved in different cellul... more High throughput technologies have characterized a multitude of genes involved in different cellular process. These are controlled by complex regulatory mechanism involving the gene products, forming an intricate gene regulatory network. A unified systems approach is needed to understand the dynamics of such an intriguing network. Many different approaches have been used to model and simulate the gene regulatory networks. This chapter discusses in brief the basic concept involved in Bayesian and Boolean approaches for studying the gene regulatory network, citing examples from recent work in this area of computational biology.
High throughput technologies have characterized a multitude of genes involved in different cellul... more High throughput technologies have characterized a multitude of genes involved in different cellular process. These are controlled by complex regulatory mechanism involving the gene products, forming an intricate gene regulatory network. A unified systems approach is needed to understand the dynamics of such an intriguing network. Many different approaches have been used to model and simulate the gene regulatory networks. This chapter discusses in brief the basic concept involved in Bayesian and Boolean approaches for studying the gene regulatory network, citing examples from recent work in this area of computational biology.
Selection pressure governs the relative mutability and the conservedness of a protein across the ... more Selection pressure governs the relative mutability and the conservedness of a protein across the protein family. Biomolecules (DNA, RNA and proteins) continuously evolve under the effect of evolutionary pressure that arises as a consequence of the host parasite interaction. IPCS (Inositol phosphorylceramide synthase), SPL (Sphingosine-1-P lyase) and SPT (Serine palmitoyl transferase) represent three important enzymes involved in the sphingolipid metabolism of Leishmania. These enzymes are responsible for maintaining the viability and infectivity of the parasite and have been classified as druggable targets in the parasite metabolome. The present work relates to the role of selection pressure deciding functional conservedness and divergence of the drug targets. IPCS and SPL protein families appear to diverge from the SPT family. The three protein families were largely under the influence of purifying selection and were moderately conserved baring two residues in the IPCS protein whic...
Leishmania major causes cutaneous form of Leishmaniasis affecting 21 million people in developing... more Leishmania major causes cutaneous form of Leishmaniasis affecting 21 million people in developing countries. Overuse of the chemotherapeutics against leishmaniasis has resulted in the development of drug resistance in the parasite. To surmount this emerging threat we have attempted to target the surface molecules. Glycosylphosphatidylinositol is one such molecule that is present abundantly and thus our work revolves around the enzyme mannosyltransferase (GPI 14), an enzyme essential to add mannose on the glycosylphosphatidyl. It has been targeted for drug discovery on account of growing resistance to miltefosine in L. major. This paper serves as the first attempt to detect GPI 14 gene in L. major supported with modeling and molecular dynamic analysis of complete three dimensional structure of GPI 14. The functional analysis revealed multiple transmembrane regions in GPI 14 and a close phylogenetic relation with Trypanosoma species and Schistosoma mansoni with highest bootstrap value...
Background: Selection pressure governs the relative mutability and the conservedness of a protein... more Background: Selection pressure governs the relative mutability and the conservedness of a protein across the protein family. Biomolecules (DNA, RNA and proteins) continuously evolve under the effect of evolutionary pressure that arises as a consequence of the host parasite interaction. IPCS (Inositol phosphorylceramide synthase), SPL (Sphingosine-1-P lyase) and SPT (Serine palmitoyl transferase) represent three important enzymes involved in the sphingolipid metabolism of Leishmania. These enzymes are responsible for maintaining the viability and infectivity of the parasite and have been classified as druggable targets in the parasite metabolome. Results: The present work relates to the role of selection pressure deciding functional conservedness and divergence of the drug targets. IPCS and SPL protein families appear to diverge from the SPT family. The three protein families were largely under the influence of purifying selection and were moderately conserved baring two residues in the IPCS protein which were under the influence of positive selection. To further explore the selection pressure at the codon level, codon usage bias indices were calculated to analyze genes for their synonymous codon usage pattern. IPCS gene exhibited slightly lower codon bias as compared to SPL and SPT protein families. Conclusion: Evolutionary tracing of the proposed drug targets has been done with a viewpoint that the amino-acids lining the drug binding pocket should have a lower evolvability. Sites under positive selection (HIS20 and CYS30 of IPCS) should be avoided during devising strategies for inhibitor design.
Understanding network topology through embracing the global dynamical regulation of genes in an a... more Understanding network topology through embracing the global dynamical regulation of genes in an active state space rather than traditional one-gene-one trait approach facilitates the rational drug development process. Schistosomiasis, a neglected tropical disease, has glycerophospholipids as abundant molecules present on its surface. Lack of effective clinical solutions to treat pathogens encourages us to carry out systems-level studies that could contribute to the development of an effective therapy. Development of a strategy for identifying drug targets by combined genome-scale metabolic network and essentiality analyses through in silico approaches provides tantalizing opportunity to investigate the role of protein/substrate metabolism. A genome-scale metabolic network model reconstruction represents choline-phosphate cytidyltransferase as the rate limiting enzyme and regulates the rate of phosphatidylcholine (PC) biosynthesis. The uptake of choline was regulated by choline concentration, promoting the regulation of phosphocholine synthesis. In Schistosoma, the change in developmental stage could result from the availability of choline, hampering its developmental cycle. There are no structural reports for this protein. In order to inhibit the activity of choline-phosphate cytidyltransferase (CCT), it was modeled by homology modeling using 1COZ as the template from Bacillus subtilis. The transition-state stabilization and catalytic residues were mapped as 'HXGH' and 'RTEGISTT' motif. CCT catalyzes the formation of CDP-choline from phosphocholine in which nucleotidyltransferase adds CTP to phosphocholine. The presence of phosphocholine permits the parasite to survive in an immunologically hostile environment. This feature endeavors development of an inhibitor specific for cytidyltransferase in Schistosoma. Flavonolignans were used to inhibit this activity in which hydnowightin showed the highest affinity as compared to miltefosine.
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