Basic Motif Research Articles

Genetic features of avian influenza (A/H5N8) clade 2.3.4.4b isolated from quail in Egypt

Several genotypes of the highly pathogenic avian influenza (HPAI) virus H5N8 subtype within clade 2.3.4.4b continue to circulate in different species of domestic birds across Egypt. It is believed that quail contribute to virus replication and adaptation to other gallinaceous poultry species and humans. This study provides genetic characterization of the full genome of HPAI H5N8 isolated from quail in Egypt. The virus was isolated from a commercial quail farm associated with respiratory signs. To characterize the genetic features of the detected virus, gene sequencing via Sanger technology and phylogenetic analysis were performed. The results revealed high nucleotide identity with the HPAI H5N8 virus from Egypt, which has multiple basic amino acid motifs PLREKRRKR/GLF at the hemagglutinin (HA) cleavage site. Phylogenetic analysis of the eight gene segments revealed that the quail isolate is grouped with HPAI H5N8 viruses of clade 2.3.4.4b and closely related to the most recent circulating H5N8 viruses in Egypt. Whole-genome characterization revealed amino acid preferences for avian receptors with few mutations, indicating their affinity for human-like receptors and increased virulence in mammals, such as S123P, S133A, T156A and A263T in the HA gene. In addition, the sequencing results revealed a lack of markers associated with influenza antiviral resistance in the neuraminidase and matrix-2 coding proteins. The results of the present study support the spread of HPAIV H5N8 to species other than chickens in Egypt. Therefore, continuous surveillance of AIV in different bird species in Egypt followed by full genomic characterization is needed for better virus control and prevention.

Rewireable Building Blocks for Enzyme-Powered DNA Computing Networks.

Neural networks enable the processing of large, complex data sets with applications in disease diagnosis, cell profiling, and drug discovery. Beyond electronic computers, neural networks have been implemented using programmable biomolecules such as DNA; this confers unique advantages, such as greater portability, electricity-free operation, and direct analysis of patterns of biomolecules in solution. Analogous to bottlenecks in electronic computers, the computing power of DNA-based neural networks is limited by the ability to add more computing units, i.e., neurons. This limitation exists because current architectures require many nucleic acids to model a single neuron. Each additional neuron compounds existing problems such as long assembly times, high background signal, and cross-talk between components. Here, we test three strategies to solve this limitation and improve the scalability of DNA-based neural networks: (i) enzymatic synthesis for high-purity neurons, (ii) spatial patterning of neuron clusters based on their network position, and (iii) encoding neuron connectivity on a universal single-stranded DNA backbone. We show that neurons implemented via these strategies activate quickly, with a high signal-to-background ratio and process-weighted inputs. We rewired our modular neurons to demonstrate basic neural network motifs such as cascading, fan-in, and fan-out circuits. Finally, we designed a prototype two-layer microfluidic device to automate the operation of our circuits. We envision that our proposed design will help scale DNA-based neural networks due to its modularity, simplicity of synthesis, and compatibility with various neural network architectures. This will enable portable computing power for applications in portable diagnostics, compact data storage, and autonomous decision making for lab-on-a-chips.

High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor.

GDC-6036 is a covalent KRAS G12C inhibitor that demonstrates high potency and selectivity. Structurally, GDC-6036 consists of several motifs that make the analytical characterization of this molecule challenging, including a highly basic pyrrolidine motif bonded to a quinazoline ring via an ether bond and an atropisomeric carbon-carbon bond between functionalized pyridine and quinazoline groups. Structurally, the desired atropisomer was synthesized via an atroposelective Negishi coupling with very high yield. However, having a direct way to analyze and confirm the presence of the atropisomeric species remained challenging in routine analytical workflows. In this study, both variable temperature nuclear magnetic resonance (VT-NMR) and two different approaches of in-line ion mobility coupled to liquid chromatography mass spectrometry (LC-MS) workflows were evaluated for the characterization of GDC-6036 and its undesired atropisomer (Compound B) to support synthetic route development. Briefly, both VT-NMR and traveling wave ion mobility spectrometry (TWIMS) enabled by structures for lossless ion manipulation (SLIM) technology coupled to high resolution MS (HRMS) are able to elucidate the structures of the atropisomers in a complex mixture. Drift tube IMS (DTIMS) was also evaluated, but lacked the resolving power to demonstrate separation between the two species in a mixture, but did show slight differences in their arrival times when multiplexed and injected separately. The determined resolving power (Rp) by multiplexing the ions via DTIMS was 67.3 and 60.5 for GDC-6036 and Compound B, respectively, while the two peak resolving power (Rpp) was determined to be 0.41, indicating inadequate resolution between the two species. Alternatively, the SLIM-IM studies showed Rp of 103.8 and 99.4, with a Rpp of 2.64, indicating good separation between the atropisomers. Furthermore, the CCS/z for GDC-6036 and Compound B was determined to be 231.2 Å2/z and 235.0 Å2/z, respectively. Quantitative experiments demonstrate linearity (R2 >0.99) for both GDC-6036 and Compound B while maintaining separation via SLIM-IM. Spike recoveries of one atropisomer relative to the other yielded strong recoveries (98.7% to 102.5%) while maintaining reproducibility (<7% RSD). The study herein describes the analytical process for evaluating new technologies and strategies for implementation in routine biopharmaceutical characterization workflows.

저승여행신화의 인정-협상 코드 &lt;차사본풀이&gt;계 서사무가 연구

It is insisted that Chasabonpuri may have been inspired by the story of Kimchi, who served as the Jeju judge in the 17th century, or the story of Heungdeokhyeongam. However, considering that the basic motif of Chasabonpuri, which is the confrontation between this world’s judge and the underworld judge, already existed during the Tang Song Dynasty, and that there was also an oral tradition in which General Gang Gam-chan, not Heungdeokhyeongam, appeared as the solver, the formation of this shamanic myth can be traced back to before Goryeo. To understand Chasabonpuri, one should consider the narrative, and not the Kimchi judge as the motif. It is necessary to pay attention to the long history of an in-depth narrative present in Chasabonpuri, spanning from a hunting society to an agricultural and pastoral society, and from Sumerian to Tamra-Jeju mythology. The in-depth narrative involves a journey to the underworld that originates from the vision of the world of death, and the driving force that makes the protagonist's journey to the underworld possible is the gift-negotiation code. According to this code, Inanna hung herself on a peg as a gift, and consequently, Dumuzi and her sister Geshtinanna negotiated a 6-months-long cycle between this world and the next. Nishan Shaman, who is said to be the ancestor of Manchurian shamans, also enters the underworld to pick up Seorgudai Piyanggu, and using various gifts, he pleads with King Yeomra and his messenger Mongoldai Nakchu to extend Piyanggu's life. In Korean shamanic mythology, which continues from Jimgajegut to Chasabonpuri, a district magistrate in this world negotiates with King Yeomra of the underworld using gifts to save the dead from a short life. Despite detailed differences in cultural conditions and narrative composition, there is a gift-negotiation code deeply integrated in these myths. This gift-negotiation code originated from the ritual gift exchange between humans and animals in early hunting societies. Hunters offered gifts and negotiated with the gods because the animal's owner would not release the game unless gifts are offered. This gift is not a calculated act of exchange but is based on unlimited reciprocity. The gift-negotiation code repeated from the Inanna myth to the Ganglimchasa myth indicates that the rules of a hunting society based on unlimited reciprocity continue in current shaman mythology through narrative transformation.

Influence of network structure on spreading dynamics via tie range

Abstract There are various phenomena of malicious information spreading in the real society, which cause many negative impacts on the society. In order to better control the spreading, it is crucial to reveal the influence of network structure on network spreading. Motifs, as fundamental structures within a network, play a significant role in spreading. Therefore, it is of interest to investigate the influence of the structural characteristics of basic network motifs on spreading dynamics. Considering the edges of the basic network motifs in an undirected network correspond to different tie ranges, two edge removal strategies are proposed, short ties priority removal strategy and long ties priority removal strategy. The tie range represents the second shortest path length between two connected nodes. The study focuses on analyzing how the proposed strategies impact network spreading and network structure, as well as examining the influence of network structure on network spreading. Our findings indicate that the long ties priority removal strategy is most effective in controlling network spreading, especially in terms of spread range and spread velocity. In terms of network structure, the clustering coefficient and the diameter of network also have an effect on the network spreading, and the triangular structure as an important motif structure effectively inhibits the spreading.

Thermodynamic and stoichiometric laws ruling the fates of growing systems

We delve into growing open chemical reaction systems (CRSs) characterized by autocatalytic reactions within a variable volume, which changes in response to these reactions. Understanding the thermodynamics of such systems is crucial for comprehending biological cells and constructing protocells because it sheds light on the physical conditions necessary for their self-replication. Building on our recent work, where we developed a thermodynamic theory for growing CRSs featuring basic autocatalytic motifs with regular stoichiometric matrices, we now expand this theory to include scenarios where the stoichiometric matrix has a nontrivial left kernel space. This extension introduces conservation laws, which limit the variations in chemical species due to reactions, thereby confining the system's possible states to those compatible with its initial conditions. By considering both thermodynamic and stoichiometric constraints, we clarify the environmental and initial conditions that dictate the CRSs' fate—whether they grow, shrink, or reach equilibrium. We also find that the conserved quantities significantly influence the equilibrium state achieved by a growing CRS. These results are derived independently of specific thermodynamic potentials or reaction kinetics, therefore underscoring the fundamental impact of conservation laws on the growth of the system. Published by the American Physical Society 2024

The polarity protein Yurt associates with the plasma membrane via basic and hydrophobic motifs embedded in its FERM domain.

The subcellular distribution of the polarity protein Yurt (Yrt) is subjected to a spatio-temporal regulation in Drosophila melanogaster embryonic epithelia. After cellularization, Yrt binds to the lateral membrane of ectodermal cells and maintains this localization throughout embryogenesis. During terminal differentiation of the epidermis, Yrt accumulates at septate junctions and is also recruited to the apical domain. Although the mechanisms through which Yrt associates with septate junctions and the apical domain have been deciphered, how Yrt binds to the lateral membrane remains as an outstanding puzzle. Here, we show that the FERM domain of Yrt is necessary and sufficient for membrane localization. Our data also establish that the FERM domain of Yrt directly binds negatively charged phospholipids. Moreover, we demonstrate that positively charged amino acid motifs embedded within the FERM domain mediates Yrt membrane association. Finally, we provide evidence suggesting that Yrt membrane association is functionally important. Overall, our study highlights the molecular basis of how Yrt associates with the lateral membrane during the developmental time window where it is required for segregation of lateral and apical domains.

Genomic resources of aquatic Lepidoptera, Elophila obliteralis and Hyposmocoma kahamanoa, reveal similarities with Trichoptera in amino acid composition of major silk genes.

While most species of butterflies and moths (Lepidoptera) have entirely terrestrial life histories, ∼0.5% of the described species are known to have an aquatic larval stage. Larvae of aquatic Lepidoptera are similar to caddisflies (Trichoptera) in that they use silk to anchor themselves to underwater substrates or to build protective cases. However, the physical properties and genetic elements of silks in aquatic Lepidoptera remain unstudied, as most research on lepidopteran silk has focused on the commercially important silkworm, Bombyx mori. Here, we provide high-quality PacBio HiFi genome assemblies of 2 distantly-related aquatic Lepidoptera species [Elophila obliteralis (Pyraloidea: Crambidae) and Hyposmocoma kahamanoa (Gelechioidea: Cosmopterigidae)]. As a step toward understanding the evolution of underwater silk in aquatic Lepidoptera, we used the genome assemblies and compared them to published genetic data of aquatic and terrestrial Lepidoptera. Sequences of the primary silk protein, h-fibroin, in aquatic moths have conserved termini and share a basic motif structure with terrestrial Lepidoptera. However, these sequences were similar to aquatic Trichoptera in that the percentage of positively and negatively charged amino acids was much higher than in terrestrial Lepidoptera, indicating a possible adaptation of silks to aquatic environments.

Collective dynamics and shot-noise-induced switching in a two-population neural network.

Neural mass models are a powerful tool for modeling of neural populations. Such models are often used as building blocks for the simulation of large-scale neural networks and the whole brain. Here, we carry out systematic bifurcation analysis of a neural mass model for the basic motif of various neural circuits, a system of two populations, an excitatory, and an inhibitory ones. We describe the scenarios for the emergence of complex collective behavior, including chaotic oscillations and multistability. We also compare the dynamics of the neural mass model and the exact microscopic system and show that their agreement may be far from perfect. The discrepancy can be interpreted as the action of the so-called shot noise originating from finite-size effects. This shot noise can lead to the blurring of the neural mass dynamics or even turn its attractors into metastable states between which the system switches recurrently.

Abstract 3051: JunAP, a peptide antagonist against the activator protein 1 transcription factor complex, demonstrates cancer cell cytotoxicity and reduced invasion in vitro and tumor regression in vivo in TNBC models

Abstract The activator protein 1 (AP-1) transcription factor is a dimeric complex consisting of proteins from the JUN, FOS, MAF, and ATF families. AP-1 complexes have been identified as novel therapeutic targets in cancer due to their role in tumor growth, invasion, metastasis, angiogenesis and chemoresistance. Dimerization of components of the AP-1 complex via leucine zipper domain interactions is required for DNA binding and subsequent transcriptional activity. We designed a peptide (Jun antagonizing peptide, JunAP) targeting the basic leucine zipper motif of AP-1 to antagonize AP-1 complex formation and prevent associated activity. Fluorescence polarization and DNA ELISA assays demonstrate target binding and selectivity of JunAP towards AP-1 family members, co-immunoprecipitation experiments reveal that JunAP blocks protein-protein interactions between cJun and its key binding partners, and reporter assays confirm inhibition of AP-1 transcriptional activity in vitro. Pathway analysis of RNA sequencing data confirmed by qPCR analysis shows that JunAP disrupts key pathways required for cell survival and migration. Corresponding functional in vitro assays reveal that JunAP exhibits an inhibitory effect on invasion in Boyden chamber assays and demonstrates potent cytotoxicity in Jun-dependent cells. Further, in a BT549 triple negative breast cancer subcutaneous xenograft model, administration of JunAP results in tumor regression, demonstrating the anti-cancer potential of targeting the AP-1 complex. In summary, these data support JunAP as a potent peptide antagonist of the AP-1 transcription factor family that warrants further development as a potential therapeutic option for AP-1 driven tumors. Citation Format: Karen Mendelson, Zachary F. Mattes, Siok Leong, Ricardo Ramirez, Mark Koester, Claudio Scuoppo, Julia Diehl, Erin Gallagher, Jerel Gonzales, Franco Abbate, Lila Ghamsari, Gene Merutka, Barry J. Kappel, Abi Vainstein-Haras, Jim A. Rotolo. JunAP, a peptide antagonist against the activator protein 1 transcription factor complex, demonstrates cancer cell cytotoxicity and reduced invasion in vitro and tumor regression in vivo in TNBC models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3051.

Functional subtypes of synaptic dynamics in mouse and human

Synapses preferentially respond to particular temporal patterns of activity with a large degree of heterogeneity that is informally or tacitly separated into classes. Yet, the precise number and properties of such classes are unclear. Do they exist on a continuum and, if so, when is it appropriate to divide that continuum into functional regions? In a large dataset of glutamatergic cortical connections, we perform model-based characterization to infer the number and characteristics of functionally distinct subtypes of synaptic dynamics. In rodent data, we find five clusters that partially converge with transgenic-associated subtypes. Strikingly, the application of the same clustering method in human data infers a highly similar number of clusters, supportive of stable clustering. This nuanced dictionary of functional subtypes shapes the heterogeneity of cortical synaptic dynamics and provides a lens into the basic motifs of information transmission in the brain.

Self-Assembled Materials Based on Fully Aromatic Peptides: The Impact of Tryptophan, Tyrosine, and Dopa Residues.

Peptides are able to self-organize in structural elements including cross-β structures. Taking advantage of this tendency, in the last decades, peptides have been scrutinized as molecular elements for the development of multivalent supramolecular architectures. In this context, different classes of peptides, also with completely aromatic sequences, were proposed. Our previous studies highlighted that the (FY)3 peptide, which alternates hydrophobic phenylalanine and more hydrophilic tyrosine residues, is able to self-assemble, thanks to the formation of both polar and apolar interfaces. It was observed that the replacement of Phe and Tyr residues with other noncoded aromatic amino acids like 2-naphthylalanine (Nal) and Dopa affects the interactions among peptides with consequences on the supramolecular organization. Herein, we have investigated the self-assembling behavior of two novel (FY)3 analogues with Trp and Dopa residues in place of the Phe and Tyr ones, respectively. Additionally, PEGylation of the N-terminus was analyzed too. The supramolecular organization, morphology, and capability to gel were evaluated using complementary techniques, including fluorescence, Fourier transform infrared spectroscopy, and scanning electron microscopy. Structural periodicities along and perpendicular to the fiber axis were detected by grazing incidence wide-angle X-ray scattering. Finally, molecular dynamics studies provided interesting insights into the atomic structure of the cross-β that constitutes the basic motif of the assemblies formed by these novel peptide systems.

«Собирание существования» как один из осевых мотивов творчества Б. Пастернака и Р.М. Рильке

The article deals with the motivic paradigm of “collecting / packing existence” in the work of B. Pasternak. The study aims to determine its role in the lyrical and philosophical concept of the poet and to identify its structure and connection with the creative system of R.M. Rilke. In the first part of the study, the motif of “collecting existence” appears as one of the basic Pasternak motifs. Further — as a point of contact between the creative concepts of Pasternak and Rainer Maria Rilke. That is how the paradigm forms an intersystem metatext. Rilke’s metatext is also conceptual and relates to the philosophical system of S. Kierkegaard, respected by both poets. Then, based on the analysis of the sub-paradigms of the motif of “collecting existence” in the work of B. Pasternak, it is proved that the paradigm has one of the essential roles in revealing autosystem metatext character of his lyrics, artistic, journalistic, and epistolary prose and forms a poetic and philosophical field. Its repeated reproduction in different genres implements an existential understanding of time and the objectness of the world. It combines the motifs of specific actions, such as collecting cars on the train, things on the road, and people in crowds and gatherings, and imaginative motifs: a collection of abstract realities in man, time, space, and the realities of nature into a picture of the world, both an instantaneous one and imprinted in art for centuries.

Fundamental patterns of signal propagation in complex networks.

Various disasters stem from minor perturbations, such as the spread of infectious diseases and cascading failure in power grids. Analyzing perturbations is crucial for both theoretical and application fields. Previous researchers have proposed basic propagation patterns for perturbation and explored the impact of basic network motifs on the collective response to these perturbations. However, the current framework is limited in its ability to decouple interactions and, therefore, cannot analyze more complex structures. In this article, we establish an effective, robust, and powerful propagation framework under a general dynamic model. This framework reveals classical and dense network motifs that exert critical acceleration on signal propagation, often reducing orders of magnitude compared with conclusions generated by previous work. Moreover, our framework provides a new approach to understand the fundamental principles of complex systems and the negative feedback mechanism, which is of great significance for researching system controlling and network resilience.

A Model Halogen-Bonded Network as a Potential Tube-like Host for Li+: A DFT Study

The formation of a halogen-bonded network using four NHX-(CH2)3-NX-(CH2)3-NHX molecules (X = Cl, Br, or I) is investigated using DFT. The self-assembly of the four basic motifs results in a tube-like structure with C4h symmetry, with one halogen-bonded network located at each end of the structure and one at its center. Each halogen-bonded network has four quasi-planar N-X···N interactions with binding energies that increase with the size of X. The structure is found to bind Li+ at each of the halogen-bonded networks, albeit more strongly at its center. The binding of Li+ is driven by halogen atom lone pairs that produce a rich electron density orthogonal to the halogen bond. The presence and strength of the interactions are further examined using AIM and NBO calculations. Lastly, IRC calculations are performed to examine the transitions between the Li+ complex minima and, thus, the potential for transporting the metal ion from one end of the tube to the other. Based on the tetrameric structure, a model intramolecular structure is built and considered as a potential host for Li+. In this case, the central intermolecular N-X···N network is replaced by an intramolecular Si-C≡C-Si network. Interestingly, both intermolecular and intramolecular structures exhibit similar Li+ binding abilities.

AlliumDB: a central portal for comparative and functional genomics in Allium.

The genus Allium belongs to the botanical family Amaryllidaceae and includes economically important crops such as onion, garlic, bunching onion, and leek, used as vegetables, spices, and traditional medicines. The large sizes of Allium genomes hamper the genetic dissection of agronomically important traits and molecular breeding. With the growing accumulation of genomic, resequencing, transcriptome, and phenotypic data, the demand for an integrative Allium database is increasing. Here we present a user-friendly database, AlliumDB (https://allium.qau.edu.cn), as a functional genomics hub integrating public and in-house data. The database contains all currently available nuclear and organelle genomes for Allium species, with genes comprehensively annotated based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, orthology, gene families, protein families (Pfam), and non-coding RNA families (Rfam). Transcriptome and variation profiles are integrated into dynamic visualization tools. We took phenotypic photographs and generated trait records for hundreds of Allium germplasms collected worldwide, which are included in the database. We incorporated JBrowse for the visualization of gene structures, RNA sequencing data, and variation data. Analysis tools such as the basic local alignment search tool (BLAST), sequence fetch, enrichment, and motif analyses are available to explore potential gene functions. This database incorporates comprehensive Allium genotypic and phenotypic datasets. As the community assembles new genomes and generates resequencing data for Allium germplasms, the database will be improved and continuously updated with these multi-omics data and comparative genomic studies. We expect the AlliumDB database to become a key resource for the study of Allium crops.

Sumerian poem about Lugalbanda and parallels for one of its episodes

This article begins with the paraphrase of the Sumerian poems “Lugalbanda in the Mountain Cave” and “Lugalbanda and the Anzu Bird”. The retelling is made by Rim M. Nurullin who consulted the recent studies related to these texts. A parallel between “Lugalbanda in the Mountain Cave” and the Rigveda is specifically discussed. Further, a classification of episodes found in the narratives recorded in Eurasia and America ca. A.D. 1850-1950 that contain the same motifs as the episode of Lugalbanda’s meeting with the Anzu bird is provided. The area distribution of two main variants is revealed. According to the first one, a man kills a serpent that was going to devour the nestlings of a mighty bird, and the grateful bird helps him. This variant is attested from Algeria to India and from Manchuria to the Carpathian-Balkan region. The American parallels also exist. According to the second variant, the man cares for nestlings (feeds them, covers from a storm, etc.) while the serpent is not mentioned. In the Sumerian poem, the hero decorates the nestlings. Concerning late traditions, such an episode being rare in the south (from the Maghreb to India) is predominant among the Eastern Slavs, Baltic Finns, and probably Balts. Rare Siberian cases are scattered from the Northern Khanty to Asiatic Eskimo. Considering the American parallels, the first variant looks like the earlier one. The basic motif of a hero who helps the nestlings is an example of a narrative element that had spread at least in the Terminal Paleolithic and has survived until recent times when it was incorporated into the fairytales.

Toward determining amyloid fibril structures using experimental constraints from Raman spectroscopy

We present structural models for three different amyloid fibril polymorphs prepared from amylin20–29 (sequence SNNFGAILSS) and amyloid-β25–35 (Aβ25–35) (sequence GSNKGAIIGLM) peptides. These models are based on the amide C=O bond and Ramachandran ψ-dihedral angle data from Raman spectroscopy, which were used as structural constraints to guide molecular dynamics (MD) simulations. The resulting structural models indicate that the basic structural motif of amylin20–29 and Aβ25–35 fibrils is extended β-strands. Our data indicate that amylin20–29 forms both antiparallel and parallel β-sheet fibril polymorphs, while Aβ25–35 forms a parallel β-sheet fibril structure. Overall, our work lays the foundation for using Raman spectroscopy in conjunction with MD simulations to determine detailed molecular-level structural models of amyloid fibrils in a manner that complements gold-standard techniques, such as solid-state nuclear magnetic resonance and cryogenic electron microscopy.

Opposition to Synchronization of Bistable State in Motif Configuration of Rössler Chaotic Oscillator Systems

This paper presents the study of the opposition to the synchronization of bistable chaotic oscillator systems in basic motif configurations. The following configurations were analyzed: Driver-response oscillator systems coupling, two driver oscillator systems to one response oscillator, and a three-oscillator systems ring unidirectional configuration. The study was conducted using the differential equations representing the piecewise linear Rössler-like electronic circuits; the initial conditions were changed to achieve a bistable characteristic Homoclinic H-type or Rössler R-type attractor. Analyzing a sweep of the initial conditions, the basin attractor was obtained. It can be observed that each system has a preferred Homoclinic chaotic attractor with any perturbation or change in initial conditions. A similarity analysis based on the coupling factor was also performed and found that the system has a preferentially Homoclinic chaotic attractor.

Disruption of the productive encounter complex results in dysregulation of DIAPH1 activity

The diaphanous-related formin, Diaphanous 1 (DIAPH1), is required for the assembly of Filamentous (F)-actin structures. DIAPH1 is an intracellular effector of the receptor for advanced glycation end products (RAGE) and contributes to RAGE signaling and effects such as increased cell migration upon RAGE stimulation. Mutations in DIAPH1, including those in the basic "RRKR" motif of its autoregulatory domain, diaphanous autoinhibitory domain (DAD), are implicated in hearing loss, macrothrombocytopenia, and cardiovascular diseases. The solution structure of the complex between the N-terminal inhibitory domain, DID, and the C-terminal DAD, resolved by NMR spectroscopy shows only transient interactions between DID and the basic motif of DAD, resembling those found in encounter complexes. Cross-linking studies placed the RRKR motif into the negatively charged cavity of DID. Neutralizing the cavity resulted in a 5-fold decrease in the binding affinity and 4-fold decrease in the association rate constant of DAD for DID, indicating that the RRKR interactions with DID form a productive encounter complex. A DIAPH1 mutant containing a neutralized RRKR binding cavity shows excessive colocalization with actin and is unresponsive to RAGE stimulation. This is the first demonstration of a specific alteration of the surfaces responsible for productive encounter complexation with implications for human pathology.