scholarly journals Chorismate synthase mediates cerebral malaria pathogenesis by eliciting salicylic acid-dependent autophagy response in parasite

Biology Open ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. bio054544
Author(s):  
Malabika Chakrabarti ◽  
Deepika Kannan ◽  
Akshay Munjal ◽  
Hadi Hasan Choudhary ◽  
Satish Mishra ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Cerebral Malaria ◽  
Critical Role ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Parasite Load ◽  
Stressed Condition ◽  
Reye's Syndrome ◽  
Chorismate Synthase ◽  
Novel Approach

ABSTRACTCerebral malaria caused by Plasmodium falciparum is the severest form of the disease resulting in the morbidity of a huge number of people worldwide. Development of effective curatives is essential in order to overcome the fatality of cerebral malaria. Earlier studies have shown the presence of salicylic acid (SA) in malaria parasite P. falciparum, which plays a critical role in the manifestation of cerebral malaria. Further, the application of SA for the treatment of acute symptoms in cerebral malaria increases the activity of iNOS leading to severe inflammation-mediated death, also called as Reye's syndrome. Therefore, modulation of the level of SA might be a novel approach to neutralize the symptoms of cerebral malaria. The probable source of parasite SA is the shikimate pathway, which produces chorismate, a precursor to aromatic amino acids and other secondary metabolites like SA in the parasite. In this work, we performed the immunological, pathological and biochemical studies in mice infected with chorismate synthase knocked-out Plasmodium berghei ANKA, which does not produce SA. Fewer cerebral outcomes were observed as compared to the mice infected with wild-type parasite. The possible mechanism behind this protective effect might be the hindrance of SA-mediated induction of autophagy in the parasite, which helps in its survival in the stressed condition of brain microvasculature during cerebral malaria. The absence of SA leading to reduced parasite load along with the reduced pathological symptoms contributes to less fatality outcome by cerebral malaria.

scholarly journals Uncovering the Role of PhzC as DAHP Synthase in Shikimate Pathway of Pseudomonas chlororaphis HT66

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 86
Author(s):  
Songwei Wang ◽  
Dongliang Liu ◽  
Muhammad Bilal ◽  
Wei Wang ◽  
Xuehong Zhang
Keyword(s):  
Feedback Inhibition ◽  
Critical Role ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Pseudomonas Chlororaphis ◽  
Dahp Synthase ◽  
E Coli ◽  
Allosteric Control ◽  
Loop Region

DAHP synthase catalyzes the first step in the shikimate pathway, deriving the biosynthesis of aromatic amino acids (Trp, Phe and Tyr), phenazine-1-carboxamide, folic acid, and ubiquinone in Pseudomonas chlororaphis. In this study, we identified and characterized one DAHP synthase encoding gene phzC, which differs from the reported DAHP synthase encoding genes aroF, aroG and aroH in E. coli. PhzC accounts for approximately 90% of the total DAHP synthase activities in P. chlororaphis HT66 and plays the most critical role in four DAHP synthases in the shikimate pathway. Inactivation of phzC resulted in the reduction of PCN production by more than 90%, while the absence of genes aroF, aroG and aroH reduced PCN yield by less than 15%, and the production of PCN was restored after the complementation of gene phzC. Moreover, the results showed that phzC in P. chlororaphis HT66 is not sensitive to feedback inhibition. This study demonstrated that gene phzC is essential for PCN biosynthesis. The expression level of both phzC and phzE genes are not inhibited in feedback by PCN production due to the absence of a loop region required for allosteric control reaction. This study highlighted the importance of PhzC and applying P. chlororaphis for shikimate pathway-derived high-value biological production.

scholarly journals Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 705
Author(s):  
Awdhesh Kumar Mishra ◽  
Kwang-Hyun Baek
Keyword(s):  
Salicylic Acid ◽  
Bacterial Species ◽  
Shikimate Pathway ◽  
Gene Clusters ◽  
Defense Responses ◽  
Biosynthetic Gene ◽  
Biosynthetic Enzyme ◽  
Biosynthetic Gene Clusters ◽  
Acid Biosynthesis ◽  
Common Precursor

Salicylic acid (SA) is an active secondary metabolite that occurs in bacteria, fungi, and plants. SA and its derivatives (collectively called salicylates) are synthesized from chorismate (derived from shikimate pathway). SA is considered an important phytohormone that regulates various aspects of plant growth, environmental stress, and defense responses against pathogens. Besides plants, a large number of bacterial species, such as Pseudomonas, Bacillus, Azospirillum, Salmonella, Achromobacter, Vibrio, Yersinia, and Mycobacteria, have been reported to synthesize salicylates through the NRPS/PKS biosynthetic gene clusters. This bacterial salicylate production is often linked to the biosynthesis of small ferric-ion-chelating molecules, salicyl-derived siderophores (known as catecholate) under iron-limited conditions. Although bacteria possess entirely different biosynthetic pathways from plants, they share one common biosynthetic enzyme, isochorismate synthase, which converts chorismate to isochorismate, a common precursor for synthesizing SA. Additionally, SA in plants and bacteria can undergo several modifications to carry out their specific functions. In this review, we will systematically focus on the plant and bacterial salicylate biosynthesis and its metabolism.

scholarly journals Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase α subunit

2010 ◽  
Vol 135 (2) ◽  
pp. 115-134 ◽  
Author(s):  
Susan Meier ◽  
Neslihan N. Tavraz ◽  
Katharina L. Dürr ◽  
Thomas Friedrich
Keyword(s):  
Binding Site ◽  
Critical Role ◽  
Aromatic Amino Acids ◽  
Cation Binding ◽  
Carboxy Terminus ◽  
Leakage Currents ◽  
Α Subunit ◽  
Inward Currents ◽  
The Common ◽  
Carboxy Terminal

The Na+/K+-ATPase mediates electrogenic transport by exporting three Na+ ions in exchange for two K+ ions across the cell membrane per adenosine triphosphate molecule. The location of two Rb+ ions in the crystal structures of the Na+/K+-ATPase has defined two “common” cation binding sites, I and II, which accommodate Na+ or K+ ions during transport. The configuration of site III is still unknown, but the crystal structure has suggested a critical role of the carboxy-terminal KETYY motif for the formation of this “unique” Na+ binding site. Our two-electrode voltage clamp experiments on Xenopus oocytes show that deletion of two tyrosines at the carboxy terminus of the human Na+/K+-ATPase α2 subunit decreases the affinity for extracellular and intracellular Na+, in agreement with previous biochemical studies. Apparently, the ΔYY deletion changes Na+ affinity at site III but leaves the common sites unaffected, whereas the more extensive ΔKETYY deletion affects the unique site and the common sites as well. In the absence of extracellular K+, the ΔYY construct mediated ouabain-sensitive, hyperpolarization-activated inward currents, which were Na+ dependent and increased with acidification. Furthermore, the voltage dependence of rate constants from transient currents under Na+/Na+ exchange conditions was reversed, and the amounts of charge transported upon voltage pulses from a certain holding potential to hyperpolarizing potentials and back were unequal. These findings are incompatible with a reversible and exclusively extracellular Na+ release/binding mechanism. In analogy to the mechanism proposed for the H+ leak currents of the wild-type Na+/K+-ATPase, we suggest that the ΔYY deletion lowers the energy barrier for the intracellular Na+ occlusion reaction, thus destabilizing the Na+-occluded state and enabling inward leak currents. The leakage currents are prevented by aromatic amino acids at the carboxy terminus. Thus, the carboxy terminus of the Na+/K+-ATPase α subunit represents a structural and functional relay between Na+ binding site III and the intracellular cation occlusion gate.

scholarly journals Genome-Wide Identification, Evolutionary And Expression Analyses of LEA Gene Family In Peanut (Arachis Hypogaea L.)

2021 ◽  
Author(s):  
RuoLan Huang ◽  
Dong Xiao ◽  
Xin Wang ◽  
Yi Shen ◽  
Jie Zhan ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Abiotic Stress ◽  
Stress Response ◽  
Gene Family ◽  
Segmental Duplication ◽  
Abiotic Stresses ◽  
Tandem Duplication ◽  
Critical Role ◽  
Recognition Sites ◽  
Genome Wide

Abstract Background: Late embryogenesis abundant (LEA) proteins are a group of highly hydrophilic glycine-rich proteins, which accumulate in the late stage of seed maturation and are associated with many abiotic stresses. However, few peanut LEA genes had been reported, and the research on the number, location, structure, molecular phylogeny and expression of AhLEAs was very limited. Results: In this study, 126 LEA genes were identified in the peanut genome through genome-wide analysis and were further divided into eight groups. Sequence analysis showed that most of the AhLEAs (85.7 %) had no or only one intron. LEA genes were randomly distributed on 20 chromosomes. Compared with tandem duplication, segmental duplication played a more critical role in AhLEAs amplication, and 93 segmental duplication AhLEAs and 5 pairs of tandem duplication genes were identified. Synteny analysis showed that some AhLEAs genes come from a common ancestor, and genome rearrangement and translocation occurred among these genomes. Almost all promoters of LEAs contain ABRE, MYB recognition sites, MYC recognition sites, and ERE cis-acting elements, suggesting that the LEA genes were involved in stress response. Gene expression analyses revealed that most of the LEAs were expressed in the late stages of peanut embryonic development. LEA3 (AH16G06810.1, AH06G03960.1), and Dehydrin (AH07G18700.1, AH17G19710.1) were highly expressed in roots, stems, leaves and flowers. Moreover, 100 AhLEAs were involved in response to drought, low-temperature, or Al stresses. Some LEAs that were regulated by different abiotic stresses were also regulated by hormones including ABA, brassinolide, ethylene and salicylic acid. Interestingly, AhLEAs that were up-regulated by ethylene and salicylic acid showed obvious subfamily preferences.Conclusions: AhLEAs are involved in abiotic stress response, and segmental duplication plays an important role in the evolution and amplification of AhLEAs. The genome-wide identification, classification, evolutionary and expression analyses of the AhLEA gene family provide a foundation for further exploring the LEA genes’ function in response to abiotic stress in peanuts.

scholarly journals Adaptation of bacteria to glyphosate: a microevolutionary perspective of the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase

2020 ◽  
Author(s):  
Miia J. Rainio ◽  
Suvi Ruuskanen ◽  
Marjo Helander ◽  
Kari Saikkonen ◽  
Irma Saloniemi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Active Site ◽  
Shikimate Pathway ◽  
Aromatic Amino Acids ◽  
Ecosystem Functions ◽  
Epsp Synthase

ABSTRACTGlyphosate is the leading herbicide worldwide, but it also affects prokaryotes because it targets the central enzyme (EPSPS) of the shikimate pathway in the synthesis of the three essential aromatic amino acids in autotrophs. Our results reveal that bacteria easily become resistant to glyphosate through changes in the EPSPS active site. This indicates the importance of examining how glyphosate affects microbe-mediated ecosystem functions and human microbiomes.

Measuring mono-word termhood by rank difference via corpus comparison

Terminology ◽  
2008 ◽  
Vol 14 (2) ◽  
pp. 204-229 ◽  
Author(s):  
Chunyu Kit ◽  
Xiaoyue Liu
Keyword(s):  
Ad Hoc ◽  
Critical Role ◽  
Novel Approach ◽  
Rank Difference ◽  
Special Knowledge ◽  
British National Corpus ◽  
Automatic Term Recognition ◽  
Core Issues ◽  
Term Candidate ◽  
National Corpus

Terminology as a set of concept carriers crystallizes our special knowledge about a subject. Automatic term recognition (ATR) plays a critical role in the processing and management of various kinds of information, knowledge and documents, e.g., knowledge acquisition via text mining. Measuring termhood properly is one of the core issues involved in ATR. This article presents a novel approach to termhood measurement for mono-word terms via corpus comparison, which quantifies the termhood of a term candidate as its rank difference in a domain and a background corpus. Our ATR experiments to identify legal terms in Hong Kong (HK) legal texts with the British National Corpus (BNC) as background corpus provide evidence to confirm the validity and effectiveness of this approach. Without any prior knowledge and ad hoc heuristics, it achieves a precision of 97.0% on the top 1000 candidates and a precision of 96.1% on the top 10% candidates that are most highly ranked by the termhood measure, illustrating a state-of-the-art performance on mono-word ATR in the field.

Towards Process-of-Care Aware Emergency Department Information Systems

2011 ◽  
pp. 241-254
Author(s):  
Andrzej S. Ceglowski ◽  
Leonid Churilov
Keyword(s):  
Information Systems ◽  
Critical Role ◽  
Process Models ◽  
Practical Significance ◽  
Patient Treatment ◽  
Process Of Care ◽  
Novel Approach ◽  
Patient Complexity ◽  
Injured Patients

The critical role of emergency departments (EDs) as the first point of contact for ill and injured patients has presented significant challenges for the elicitation of detailed process models. Patient complexity has limited the ability of ED information systems (EDIS) in prediction of patient treatment and patient movement. This article formulates a novel approach to building EDIS Activity Views that paves the way for EDIS that can predict patient workflow. The resulting Activity View pertains to what is being done, rather than what experts think is being done. The approach is based on analysis of data that is routinely recorded during patient treatment. The practical significance of the proposed approach is clinically acceptable, verifiable, and statistically valid process-oriented clusters of ED activities that can be used for targeted process elicitation, thus informing the design of EDIS. Its theoretical significance is in providing the new middle ground between existing soft and computational process elicitation methods.

A Novel Approach to Managing the Dynamic Nature of Semantic Relatedness

2020 ◽  
pp. 1085-1114
Author(s):  
Youngseok Choi ◽  
Jungsuk Oh ◽  
Jinsoo Park
Keyword(s):  
Computer Science ◽  
Computational Linguistics ◽  
Critical Role ◽  
Semantic Relatedness ◽  
Semantic Networks ◽  
Dynamic Semantic ◽  
Novel Approach ◽  
Flow Of Time ◽  
Novel Method ◽  
Corpus Data

This research proposes a novel method of measuring the dynamics of semantic relatedness. Research on semantic relatedness has a long history in the fields of computational linguistics, psychology, computer science, as well as information systems. Computing semantic relatedness has played a critical role in various situations, such as data integration and keyword recommendation. Many researchers have tried to propose more sophisticated techniques to measure semantic relatedness. However, little research has considered the change of semantic relatedness with the flow of time and occurrence of events. The authors' proposed method is validated by actual corpus data collected from a particular context over a specific period of time. They test the feasibility of our proposed method by constructing semantic networks by using the corpus collected during a different period of time. The experiment results show that our method can detect and manage the changes in semantic relatedness between concepts. Based on the results, the authors discuss the need for a dynamic semantic relatedness paradigm.

Towards Process-of-Care Aware Emergency Department Information Systems

2011 ◽  
pp. 1916-1929
Author(s):  
Andrzej S. Ceglowski ◽  
Leonid Churilov
Keyword(s):  
Information Systems ◽  
Critical Role ◽  
Process Models ◽  
Practical Significance ◽  
Patient Treatment ◽  
Process Of Care ◽  
Novel Approach ◽  
Patient Complexity ◽  
Injured Patients

The critical role of emergency departments (EDs) as the first point of contact for ill and injured patients has presented significant challenges for the elicitation of detailed process models. Patient complexity has limited the ability of ED information systems (EDIS) in prediction of patient treatment and patient movement. This article formulates a novel approach to building EDIS Activity Views that paves the way for EDIS that can predict patient workflow. The resulting Activity View pertains to “what is being done,” rather than “what experts think is being done.” The approach is based on analysis of data that is routinely recorded during patient treatment. The practical significance of the proposed approach is clinically acceptable, verifiable, and statistically valid process-oriented clusters of ED activities that can be used for targeted process elicitation, thus informing the design of EDIS. Its theoretical significance is in providing the new “middle ground” between existing “soft” and “computational” process elicitation methods.

A Novel Approach to Managing the Dynamic Nature of Semantic Relatedness

2016 ◽  
Vol 27 (2) ◽  
pp. 1-26 ◽  
Author(s):  
Youngseok Choi ◽  
Jungsuk Oh ◽  
Jinsoo Park
Keyword(s):  
Computational Linguistics ◽  
Critical Role ◽  
Semantic Relatedness ◽  
Semantic Networks ◽  
Dynamic Nature ◽  
Dynamic Semantic ◽  
Novel Approach ◽  
Flow Of Time ◽  
Novel Method ◽  
Corpus Data

This research proposes a novel method of measuring the dynamics of semantic relatedness. Research on semantic relatedness has a long history in the fields of computational linguistics, psychology, computer science, as well as information systems. Computing semantic relatedness has played a critical role in various situations, such as data integration and keyword recommendation. Many researchers have tried to propose more sophisticated techniques to measure semantic relatedness. However, little research has considered the change of semantic relatedness with the flow of time and occurrence of events. The authors' proposed method is validated by actual corpus data collected from a particular context over a specific period of time. They test the feasibility of our proposed method by constructing semantic networks by using the corpus collected during a different period of time. The experiment results show that our method can detect and manage the changes in semantic relatedness between concepts. Based on the results, the authors discuss the need for a dynamic semantic relatedness paradigm.

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