scholarly journals Monkeying around with venom: an increased resistance to α-neurotoxins supports an evolutionary arms race between Afro-Asian primates and sympatric cobras

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Richard J. Harris ◽  
K. Anne-Isola Nekaris ◽  
Bryan G. Fry
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Selection Pressure ◽  
Arms Race ◽  
Last Common Ancestor ◽  
Geographic Ranges ◽  
Venomous Snakes ◽  
Snake Detection ◽  
Coevolutionary Arms Race

Abstract Background Snakes and primates have a multi-layered coevolutionary history as predators, prey, and competitors with each other. Previous work has explored the Snake Detection Theory (SDT), which focuses on the role of snakes as predators of primates and argues that snakes have exerted a selection pressure for the origin of primates’ visual systems, a trait that sets primates apart from other mammals. However, primates also attack and kill snakes and so snakes must simultaneously avoid primates. This factor has been recently highlighted in regard to the movement of hominins into new geographic ranges potentially exerting a selection pressure leading to the evolution of spitting in cobras on three independent occasions. Results Here, we provide further evidence of coevolution between primates and snakes, whereby through frequent encounters and reciprocal antagonism with large, diurnally active neurotoxic elapid snakes, Afro-Asian primates have evolved an increased resistance to α-neurotoxins, which are toxins that target the nicotinic acetylcholine receptors. In contrast, such resistance is not found in Lemuriformes in Madagascar, where venomous snakes are absent, or in Platyrrhini in the Americas, where encounters with neurotoxic elapids are unlikely since they are relatively small, fossorial, and nocturnal. Within the Afro-Asian primates, the increased resistance toward the neurotoxins was significantly amplified in the last common ancestor of chimpanzees, gorillas, and humans (clade Homininae). Comparative testing of venoms from Afro-Asian and American elapid snakes revealed an increase in α-neurotoxin resistance across Afro-Asian primates, which was likely selected against cobra venoms. Through structure-activity studies using native and mutant mimotopes of the α-1 nAChR receptor orthosteric site (loop C), we identified the specific amino acids responsible for conferring this increased level of resistance in hominine primates to the α-neurotoxins in cobra venom. Conclusion We have discovered a pattern of primate susceptibility toward α-neurotoxins that supports the theory of a reciprocal coevolutionary arms-race between venomous snakes and primates.

scholarly journals Coevolution between primates and venomous snakes revealed by α-neurotoxin susceptibility

2021 ◽  
Author(s):  
Richard J. Harris ◽  
K. Anne-Isola Nekaris ◽  
Bryan G. Fry
Keyword(s):  
Brain Size ◽  
Arms Race ◽  
Arms Races ◽  
Venomous Snakes ◽  
Weak Binding ◽  
Snake Detection ◽  
History Of ◽  
Species Being ◽  
Geographical Locations ◽  
Coevolutionary Arms Race

AbstractEvidence suggests venomous snakes and primates have evolved certain traits in response to a coevolutionary arms-race. In both clades, evolved traits include an increase in brain size and enhanced vision. Lineage specific traits include in primates an inherent fear of snakes, while cobras have evolved defensive toxins, hooding, aposematism and venom spitting. To strengthen the claims of coevolution between venomous snakes and primates, more evidence of coevolved traits is needed to highlight the importance of this arms-race. We report a significantly reduced susceptibility of snake venom α-neurotoxins toward the α-1 nicotinic acetylcholine receptor orthosteric site within the catarrhine primates. This trait is particularly amplified within the clade Homininae. This relationship is supported by post-synaptic neurotoxic symptoms of envenoming relative to prey species being much lower humans due to weak binding of α-neurotoxins to human nicotinic receptors. Catarrhines are sympatric with many species of large, diurnal, neurotoxically venomous snakes and as such are likely to have had a long history of interaction with them. Conversely, the Lemuriformes and Platyrrhini are highly susceptible to binding of α-neurotoxins, which is consistent with them occupying geographical locations either devoid of venomous snakes or areas with neurotoxic snakes that are small, fossorial, and nocturnal. These data are consistent with the snake detection theory in that they follow a similar pattern of evolved traits within specific primate clades that are sympatric with venomous snakes. These results add new strong evidence in support of snakes and primates coevolving through arms-races that shaped selection pressures for both lineages.Significance StatementWe have discovered a pattern of primate susceptibility towards α-neurotoxins that supports the theory of a coevolutionary arms-race between venomous snakes and primates.

scholarly journals Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 164
Author(s):  
Lina Son ◽  
Elena Kryukova ◽  
Rustam Ziganshin ◽  
Tatyana Andreeva ◽  
Denis Kudryavtsev ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Central Loop ◽  
Acetylcholine Binding Proteins ◽  
Α7 Nachrs

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

scholarly journals Getting ahead of the Arms Race: Hothousing the Coevolution of VirusTotal with a Packer

Entropy ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 395
Author(s):  
Héctor D. Menéndez ◽  
David Clark ◽  
Earl T. Barr
Keyword(s):  
Machine Learning ◽  
Evolutionary Computation ◽  
Malware Detection ◽  
Cloud Service ◽  
False Positives ◽  
Arms Race ◽  
System Calls ◽  
A New Technique ◽  
Coevolutionary Arms Race

Malware detection is in a coevolutionary arms race where the attackers and defenders are constantly seeking advantage. This arms race is asymmetric: detection is harder and more expensive than evasion. White hats must be conservative to avoid false positives when searching for malicious behaviour. We seek to redress this imbalance. Most of the time, black hats need only make incremental changes to evade them. On occasion, white hats make a disruptive move and find a new technique that forces black hats to work harder. Examples include system calls, signatures and machine learning. We present a method, called Hothouse, that combines simulation and search to accelerate the white hat’s ability to counter the black hat’s incremental moves, thereby forcing black hats to perform disruptive moves more often. To realise Hothouse, we evolve EEE, an entropy-based polymorphic packer for Windows executables. Playing the role of a black hat, EEE uses evolutionary computation to disrupt the creation of malware signatures. We enter EEE into the detection arms race with VirusTotal, the most prominent cloud service for running anti-virus tools on software. During our 6 month study, we continually improved EEE in response to VirusTotal, eventually learning a packer that produces packed malware whose evasiveness goes from an initial 51.8% median to 19.6%. We report both how well VirusTotal learns to detect EEE-packed binaries and how well VirusTotal forgets in order to reduce false positives. VirusTotal’s tools learn and forget fast, actually in about 3 days. We also show where VirusTotal focuses its detection efforts, by analysing EEE’s variants.

Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: implication for pharmacological interventions

2015 ◽  
Vol 26 (2) ◽  
Author(s):  
Mehdi Ghasemi ◽  
Arash Hadipour-Niktarash
Keyword(s):  
Animal Models ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neurological Diseases ◽  
Juvenile Myoclonic Epilepsy ◽  
Neuronal Nicotinic Acetylcholine Receptors ◽  
Pharmacological Interventions ◽  
Nicotinic Acetylcholine ◽  
Neuronal Nachr

AbstractAccumulating evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) may play a key role in the pathophysiology of some neurological diseases such as epilepsy. Based on genetic studies in patients with epileptic disorders worldwide and animal models of seizure, it has been demonstrated that nAChR activity is altered in some specific types of epilepsy, including autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and juvenile myoclonic epilepsy (JME). Neuronal nAChR antagonists also have antiepileptic effects in pre-clinical studies. There is some evidence that conventional antiepileptic drugs may affect neuronal nAChR function. In this review, we re-examine the evidence for the involvement of nAChRs in the pathophysiology of some epileptic disorders, especially ADNFLE and JME, and provide an overview of nAChR antagonists that have been evaluated in animal models of seizure.

scholarly journals Role of the Cys Loop and Transmembrane Domain in the Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors

2016 ◽  
Vol 292 (2) ◽  
pp. 551-562 ◽  
Author(s):  
Constanza Alcaino ◽  
Maria Musgaard ◽  
Teresa Minguez ◽  
Simone Mazzaferro ◽  
Manuel Faundez ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Transmembrane Domain ◽  
Allosteric Modulation ◽  
Nicotinic Acetylcholine

Receiving the Synaptic Message

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Adrenergic Receptors ◽  
Acetylcholine Receptors ◽  
G Protein Coupled Receptors ◽  
Metabotropic Receptors ◽  
Second Messenger Systems ◽  
Psychotropic Effects ◽  
G Protein Coupled ◽  
Ionotropic And Metabotropic Receptors

Ionotropic and metabotropic receptors differ in their speed of action, the variety of effects produced after ligand-binding, and in the number of types present in the nervous system. The participation of two ionotropic glutamate receptors in synaptic plasticity is thought to be the cellular basis of learning. The actions of acetylcholine on nicotinic acetylcholine receptors present at the neuromuscular junction are described. The pharmacological profile of the GABAA receptor, central to most neural functions, is introduced. The properties of metabotropic receptors that are coupled to G proteins, termed G protein-coupled receptors (GPCRs), are detailed. Three canonical second-messenger systems through which GPCRs act are briefly described. An introduction to clinical pharmacology focused on how drugs acting on muscarinic and adrenergic receptors produce peripheral and central psychotropic effects is provided. Finally, the role of connexins and gap junctions in myelination and hearing is introduced.

Injection of Nicotine Into the Superior Colliculus Facilitates Occurrence of Express Saccades in Monkeys

1999 ◽  
Vol 82 (3) ◽  
pp. 1642-1646 ◽  
Author(s):  
Hiroshi Aizawa ◽  
Yasushi Kobayashi ◽  
Masaru Yamamoto ◽  
Tadashi Isa
Keyword(s):  
Superior Colliculus ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Marked Change ◽  
Major Change ◽  
Visually Guided ◽  
Express Saccades ◽  
Macaque Monkeys ◽  
The Relationship

To clarify the role of cholinergic inputs to the intermediate layer of the superior colliculus (SC), we examined the effect of microinjection of nicotine into the SC on visually guided saccades in macaque monkeys. After injection of 0.4–2 μl of 1–100 mM nicotine into the SC, frequency of extremely short latency saccades (express saccades; reaction time = 70–120 ms) dramatically increased, for the saccades the direction and amplitude of which were represented at the location of the injection site on the collicular map. However, no marked change was observed for the relationship between the peak velocities and the amplitudes of saccades. These results suggested that activation of nicotinic acetylcholine receptors in the SC can facilitate initiation but causes no major change in dynamics of visually guided saccades.

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