Introduction

Obulesu, Magisetty

doi:10.1016/b978-0-12-816412-9.00001-x

Cited by 2 publications

(1 citation statement)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among them, we found an anoctamin-4 , which codes for an ion channel protein involved in Ca 2+ -dependent conductance (Reichhart et al, 2019), downregulated in aflatrem-treated ants. We also detected a membrane metallo-endopeptidase ( Neprilysin ), a transmembrane protein found in neurological tissue that plays a role in tissue perception and preservation (Obulesu, 2019), which was slightly upregulated in aflatrem-treated ants. More specific to muscular function, we found 2 upregulated titins genes, which code for very large proteins that play an essential role in sarcomere function (Freiburg et al, 2000; Zhang et al, 2000).…”

Section: Resultsmentioning

confidence: 95%

28 Minutes Later: Investigating the role of aflatrem-like compounds in Ophiocordyceps parasite manipulation of zombie ants

Beckerson

Krider²,

Mohammad³

et al. 2022

Preprint

View full text Add to dashboard Cite

Parasites and their hosts often share intimate coevolutionary relationship that can lead to bizarre phenotypes over time. Ophiocordyceps is one such genus that has evolved to manipulate the behavior of its various insect and arachnid hosts, the clearest examples of which are found in ants of the Camponotus tribe, colloquially known as zombie ants. While the unusual behaviors induced during infection are well described, the molecular driving force behind these changes are still unknown. Recent genomic and transcriptomics analyses have identified several candidate secreted proteins and secondary metabolites highly upregulated during infection. Of particular interest amongst these compounds is an aflatrem-like ergot alkaloid related to the mycotoxin aflatrem known to cause neurological issues in other animals, issues collectively called staggers syndrome. To test if aflatrem-like compounds play a role in Camponotus floridanus manipulation, healthy ants were injected with purified aflatrem and their behavior was monitored for 30 minutes. RNA-Seq was also performed on the heads of aflatrem-injected ants to compare any changes at the transcriptomic level to data available for ants infected by Ophiocordyceps camponoti-floridani. Behavioral assay footage was analyzed using the machine learning tool MARGO, which showed a negative correlation between activity and speed, and dose of aflatrem. Behaviors were also scored manually, identifying a positive coloration between aflatrem dose and staggering behavioral phenotypes. RNA-seq discovered 262 genes significantly up or down regulated compared to sham injected ants. Of these genes, 108 were also differentially regulated in the heads of late-stage Ophiocordyceps-infected ants. Together, these results indicate that aflatrem-like compounds may play an important role during late-stages of infection by reducing activity in ants, keeping them in elevated microclimates optimal for the production and dispersal of spores.

show abstract

Section: Resultsmentioning

confidence: 95%

28 Minutes Later: Investigating the role of aflatrem-like compounds in Ophiocordyceps parasite manipulation of zombie ants

Beckerson

Krider²,

Mohammad³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

A Computational Study of Phenothiazine Derivatives as Acetylcholinesterase Inhibitors Targeting Alzheimer’s Disease

V.,

A.,

2025

CNSAMC

View full text Add to dashboard Cite

Background: Alzheimer’s disease is a neurodegenerative disorder that affects learning, memory and behavioral turbulence in elderly patients. Acetylcholinesterase (AChE) inhibitors act as anti-Alzheimer’s agents. Phenothiazine derivatives are considered momentous anti-Alzheimer’s agents because of their AChE inhibitory activity. The elevated levels and increased expression of this protein have been associated with Alzheimer's disease. Coumarin-fused phenothiazines have emerged as significant anti-Alzheimer's agents due to their notable receptor inhibitory activity. Objective: Some unique phenothiazine analogs were designed, and computational studies were conducted to explore their inhibitory activity against the AChE enzyme (PDB id: 4EY7) by using the Schrodinger suite-2019-4. objective: Some unique phenothiazine analogues were designed, and they had undergone computational studies to explore their inhibitory activity against AChE enzyme (PDB id: 4EY7) by using Schrodinger suite-2019-4. Methods: Docking studies were conducted by using the Glide module; binding free energies were calculated by means of the Prime MM-GBSA module, and Molecular dynamics (MD) simulation was performed by using the Desmond module of the Schrodinger suite. Glide scores were used to find out the binding affinity of the ligands with the target 4EY7. Results: The compounds exhibited enhanced hydrophobic interactions and formed hydrogen bonds, effectively impeding Acetylcholinesterase. The Glide scores for the compounds ranged from -13.4237 to -8.43439, surpassing the standard (Donepezil) with a score of -16.9898. Interestingly, a positive value was obtained for the MM-GBSA binding of the potent inhibitor. To gain insights into the dynamic behavior of the protein A8, molecular dynamics (MD) simulations were employed. Conclusion: Based on the results, the study concludes that phenothiazine derivatives show promise as acetylcholinesterase inhibitors. Compounds with notable Glide scores are poised to exhibit significant anti-Alzheimer's activity, suggesting their potential therapeutic efficacy. Further in vitro and in vivo investigations are warranted to validate and explore the therapeutic potentials of these compounds.

show abstract

Introduction

Cited by 2 publications

References 77 publications

28 Minutes Later: Investigating the role of aflatrem-like compounds in Ophiocordyceps parasite manipulation of zombie ants

28 Minutes Later: Investigating the role of aflatrem-like compounds in Ophiocordyceps parasite manipulation of zombie ants

A Computational Study of Phenothiazine Derivatives as Acetylcholinesterase Inhibitors Targeting Alzheimer’s Disease

Contact Info

Product

Resources

About