Local Motifs Research Articles

Structure prediction of stable sodium germanides at 0 and 10 GPa

In this paper we used random structure searching (AIRSS) to carry out a systematic search for crystalline Na-Ge materials at both 0 and 10 GPa. The high-throughput structural relaxations were accelerated using a machine-learned interatomic potential (MLIP) fit to density-functional theory (DFT) reference data, allowing ∼1.5 million structures to be relaxed. At ambient conditions we predict three new Zintl phases, Na3Ge2,Na2Ge, and Na9Ge4, to be stable and a number of Ge-rich layered structures to lie in close proximity to the convex hull. The known NaδGe34 clathrate and Na4Ge13 host-guest structures are found to be relatively stabilized at higher temperature by vibrational contributions to the free energy. Overall, the low-energy phases exhibit exceptional structural diversity, with the expected mixture of covalent and ionic bonding confirmed using the electron-localization function (ELF). The local Ge structural motifs present at each composition were determined using smooth overlap of atomic positions (SOAP) descriptors and the Ge-K edge was simulated for representatives of each motif, providing a direct link to experimental x-ray absorption spectroscopy (XAS). Two Ge-rich phases are predicted to be stable at 10 GPa; NaGe3 and NaGe2 have simple kagome and simple hexagonal Ge lattices respectively with Na contained in the pores. NaGe3 is isostructural with the MgB3 and MgSi3 family of kagome superconductors and remains dynamically stable at 0 GPa. Removing the Na from NaGe2 results in the hexagonal lonsdalite Ge allotrope, which has a direct band gap. Published by the American Physical Society 2024

Hidden magnetism and split off flat bands in the insulator metal transition in VO2

Transition metal d-electron oxides with an odd number of electrons per unit cell are expected to form metals with partially occupied energy bands, but exhibit in fact a range of behaviors, being either insulators, or metals, or having insulator-metal transitions. Traditional explanations involved predominantly electron-electron interactions in fixed structural symmetry. The present work focuses instead on the role of symmetry breaking local structural motifs. Viewing the previously observed V-V dimerization in VO2 as a continuous knob, reveals in density functional calculations the splitting of an isolated flat band from the broad conduction band. This leads past a critical percent dimerization to the formation of the insulating phase while lowering the total energy. In VO2 this transition is found to have a rather low energy barrier approaching the thermal energy at room temperature, suggesting energy-efficient switching in neuromorphic computing. Interestingly, sufficient V-V dimerization suppresses magnetism, leading to the nonmagnetic insulating state, whereas magnetism appears when dimerization is reduced, forming a metallic state. This study opens the way to design novel functional quantum materials with symmetry breaking-induced flat bands.

CD28 hinge used in chimeric antigen receptor (CAR) T-cells exhibits local structure and conformational exchange amidst global disorder

T-cell therapies based on chimeric antigen receptor (CAR) targeting of a tumor-specific antigen offer hope for patients with relapsed or refractory cancers. CAR hinge and transmembrane regions link antigen recognition domains to intracellular signal transduction domains. Here, we apply biophysical methods to characterize the structure and dynamic properties of the CD28 CAR hinge (CD28H) used in an FDA-approved CD19 CAR for the treatment of B-lineage leukemia/lymphoma. By using nuclear Overhauser effect spectroscopy (NOESY), which detects even transiently occupied structural motifs, we observed otherwise elusive local structural elements amidst overall disorder in CD28H, including a conformational switch from a native β-strand to a 310-helix and polyproline II helix-like structure. These local structural motifs contribute to an overall loosely formed extended geometry that could be captured by NOESY data. All FDA-approved CARs use prolines in the hinge region, which we find in CD28, and previously in CD8α, isomerize to promote structural plasticity and dynamics. These local structural elements may function in recognition and signaling events and constrain the spacing between the transmembrane and antigen recognition domains. Our study thus demonstrates a method for detecting local and transient structure within intrinsically disordered systems and moreover, our CD28H findings may inform future CAR design.

MoPPIt: De Novo Generation of Motif-Specific Binders with Protein Language Models.

The ability to precisely target specific motifs on disease-related proteins, whether conserved epitopes on viral proteins, intrinsically disordered regions within transcription factors, or breakpoint junctions in fusion oncoproteins, is essential for modulating their function while minimizing off-target effects. Current methods struggle to achieve this specificity without reliable structural information. In this work, we introduce a motif-specific PPI targeting algorithm, moPPIt, for de novo generation of motif-specific peptide binders from the target protein sequence alone. At the core of moPPIt is BindEvaluator, a transformer-based model that interpolates protein language model embeddings of two proteins via a series of multi-headed self-attention blocks, with a key focus on local motif features. Trained on over 510,000 annotated PPIs, BindEvaluator accurately predicts target binding sites given protein-protein sequence pairs with a test AUC > 0.94, improving to AUC > 0.96 when fine-tuned on peptide-protein pairs. By combining BindEvaluator with our PepMLM peptide generator and genetic algorithm-based optimization, moPPIt generates peptides that bind specifically to user-defined residues on target proteins. We demonstrate moPPIt's efficacy in computationally designing binders to specific motifs, first on targets with known binding peptides and then extending to structured and disordered targets with no known binders. In total, moPPIt serves as a powerful tool for developing highly specific peptide therapeutics without relying on target structure or structure-dependent latent spaces.

Fundamental Thermodynamic, Kinetic, and Mechanical Properties of Lithium and Its Alloys.

Lithium alloying reactions are beneficial in promoting uniform plating and stripping of lithium metal in all-solid-state batteries. First-principles calculations are performed to predict thermodynamic, kinetic, and mechanical properties of lithium and several important Li-M alloys (M = Mg, Ag, Zn, Al, Ga, In, Sn, Sb, and Bi). While the Li-Mg binary system forms a solid solution, most other lithium-metal alloys prefer stoichiometric intermetallic compounds with common local motifs that enable fast Li diffusion. Lithium and Li-rich alloys exhibit an unusually flat energy landscape along paths that connect BCC to close-packed structures like FCC and HCP, with important implications for mechanical properties. Very low migration barriers for Li diffusion that rival those of superion conductors are predicted, both in pure Li and in Li-M intermetallics. However, vacancy concentration, which is crucial for substitutional diffusion, is predicted to be low in metallic Li and most Li-M intermetallics. Compounds such as B32 LiAl and LiGa as well as D03 Li3Sb and Li3Bi exhibit structural vacancies at higher ends of their voltage windows, which together with low migration barriers leads to exceptionally high Li mobilities. In the Li-Mg solid solution, the addition of Mg is found to decrease the vacancy tracer diffusion coefficient by an order of magnitude.

Machine Learning Classification of Local Environments in Molecular Crystals.

Identifying local structural motifs and packing patterns of molecular solids is a challenging task for both simulation and experiment. We demonstrate two novel approaches to characterize local environments in different polymorphs of molecular crystals using learning models that employ either flexibly learned or handcrafted molecular representations. In the first case, we follow our earlier work on graph learning in molecular crystals, deploying an atomistic graph convolutional network combined with molecule-wise aggregation to enable per-molecule environmental classification. For the second model, we develop a new set of descriptors based on symmetry functions combined with a point-vector representation of the molecules, encoding information about the positions and relative orientations of the molecule. We demonstrate very high classification accuracy for both approaches on urea and nicotinamide crystal polymorphs and practical applications to the analysis of dynamical trajectory data for nanocrystals and solid-solid interfaces. Both architectures are applicable to a wide range of molecules and diverse topologies, providing an essential step in the exploration of complex condensed matter phenomena.

Local Structural Features Elucidate Crystallization of Complex Structures.

Complex crystal structures are composed of multiple local environments, and how this type of order emerges spontaneously during crystal growth has yet to be fully understood. We study crystal growth across various structures and along different crystallization pathways, using self-assembly simulations of identical particles that interact via multiwell isotropic pair potentials. We apply an unsupervised machine learning method to features from bond-orientational order metrics to identify different local motifs present during a given structure's crystallization process. In this manner, we distinguish different crystallographic sites in highly complex structures. Tailoring this order parameter to structures of varying complexity and coordination number, we study the emergence of local order along a multistep crystal growth pathway─from a low-density fluid to a high-density, supercooled amorphous liquid droplet and to a bulk crystal. We find a consistent under-coordination of the liquid relative to the average coordination number in the bulk crystal. We use our order parameter to analyze the geometrically frustrated growth of a Frank-Kasper phase and discover how structural defects compete with the formation of crystallographic sites that are more high-coordinated than the liquid environments. The method presented here for classifying order on a particle-by-particle level has broad applicability to future studies of structural self-assembly and crystal growth, and they can aid in the design of building blocks and for targeting pathways of formation of soft-matter structures.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

The rise of Q-pop in Kazakhstan and its impact on national identity

This study delves into the influence of the Korean Wave on the emergence of Q-pop in Kazakhstan, examining its impact on the country's cultural landscape and national identity. Stemming from the worldwide appeal of Korean culture, Q-pop merges local Kazakh motifs with global trends, leaving a significant mark on Kazakhstan's music industry and culture. This study highlights how Q-pop influences Kazakhstani youth's sense of national pride, spreading across Central Asia and countering Russian musical dominance. The research aims to investigate the role of Q-pop in reinforcing Kazakh cultural ties among various demographic groups, thereby enriching our comprehension of national identity in the country. This study utilized a quantitative research methodology, employing an online survey and snowball sampling technique to gather statistically significant results and insights into the rise of Q-pop and its intricate relation with national identity in Kazakhstan. Through exploring Q-pop's interaction with different cultural contexts, this study aims to shed light on the dynamics of cultural adaptation, fusion, and national identity construction in Kazakhstan, paying special attention to the intricate effects of gender and geographical factors. It highlights the critical balance between preserving Kazakh traditions and aligning with the younger generation's preferences.

Formation of a zirconium oxide crystal nucleus in the initial nucleation stage in aluminosilicate glass investigated by X-ray multiscale analysis

Understanding the nucleation mechanism in glass is crucial for the development of new glass-ceramic materials. Herein, we report the structure of a commercially important glass-ceramic ZrO2-doped lithium aluminosilicate system during its initial nucleation stage. We conducted an X-ray multiscale analysis, and this analysis was used to observe the structure from the atomic to the nanometer scale by using diffraction, small-angle scattering, absorption, and anomalous scattering techniques. The inherent phase separation between the Zr-rich and Zr-poor regions in the pristine glass was enhanced by thermal treatment without changing the spatial geometry at the nanoscale. Element-specific pair distribution function analysis using anomalous X-ray scattering data showed the formation of a liquid ZrO2-like local structural motif and edge sharing between the ZrOx polyhedra and (Si/Al)O4 tetrahedra during the initial nucleation stage. Furthermore, the local structure of the Zr4+ ions resembled a cubic or tetragonal ZrO2 crystalline phase and formed after 2 h of annealing the pristine glass. Therefore, the Zr-centric periodic structure formed in the early stage of nucleation was potentially the initial crystal nucleus for the Zr-doped lithium aluminosilicate glass-ceramic.

Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7.

Biallelic TOE1 variants can cause pontocerebellar hypoplasia type 7 (PCH7), a condition characterized by pontocerebellar hypoplasia with genital abnormality. TOE1 is a 3'-exonuclese for 3'-end maturation in small nuclear RNA. TOE1 pathogenic variants have been reported at the DEDD catalytic domain and zinc finger motif. Here, we describe a PCH7 patient with novel compound heterozygous TOE1 variants and a detailed clinical course. The patient was a 3-year-old female and showed developmental delay without cerebellar ataxic behavior. Head MRI revealed delayed myelination without pontocerebellar hypoplasia at 9 months of age. Progressive pontocerebellar atrophy was prominent at follow-up MRI. Cerebral abnormalities are characteristic features of PCH7 before pontocerebellar atrophy is observed. One variant, p.Arg331*, was located at the nuclear localization motif (NLM) and partially escaped from nonsense-mediated decay. This variant affected nuclear localization in mutant expressing cells, thus, the TOE1 variant at NLM leads to TOE1 dysfunction associated with nuclear mis-localization.

Batik Tambun Bungai Penciptaan Motif Lokal Untuk Kejatidirian Eknonomi Kreatif Kalimantan Tengah

This research aims to create local batik motif. This research was focused on creating local Tambun Bungai batik motifs for the creative economic identity of Central Kalimantan Province in supporting SDGs in regional development. This research uses a design creation approach that is implemented on fabric using a digital batik printing process. The design creation research methods involves the following steps. (1) identification (2) research (3) idea formulation (4) prototype (5) selection (6) implementation (7) evaluation. The results yield are typical Tambun Bungai batik which has its own uniqueness, inspired by the richness of the natural landscape, traditional art and has bold color patterns that convey a strong impression of the philosophical values ​​inherent in Central Kalimantan batik motifs as well as being an effective regional promotional media. Keywords: Batik, Dayak, Creative economy, Central Kalimantan

Temperature-induced suppression of structural disproportionation in paramagnetic quantum materials

With the development of electronic structure theory, a new class of materials—quantum ones—has been recognized by the community. Traditionally, it has been believed that the properties of such compounds cannot be described within the framework of modern density functional theory, and indeed, more advanced post-mean-field theory methods are needed. Motivated by this, herein, we develop a fundamental understanding of such complex materials using the example of paramagnetic YNiO3, which is experimentally known to exhibit metal-to-insulator phase transition. We show that this material has a temperature-dependent distribution of local motifs. Thus, while at low temperatures, YNiO3 has distinct structural disproportionation with the formation of large and small octahedra, as the temperature increases, this disproportionation is suppressed. We also explain the paramagnetic monoclinic to paramagnetic orthorhombic phase transition within the double-well to single-well energy profile, predicting the variation in the corresponding energy profile as a function of octahedral size distribution. In this way, we demonstrate a fundamental understanding of structural phase transitions in quantum materials, giving insights into how they can be used for different applications and what minimum level of theory is needed to describe such types of complex materials at finite temperatures.

Neural waves and computation in a neural net model I: Convolutional hierarchies.

The computational resources of a neuromorphic network model introduced earlier are investigated in the context of such hierarchical systems as the mammalian visual cortex. It is argued that a form of ubiquitous spontaneous local convolution, driven by spontaneously arising wave-like activity-which itself promotes local Hebbian modulation-enables logical gate-like neural motifs to form into hierarchical feed-forward structures of the Hubel-Wiesel type. Extra-synaptic effects are shown to play a significant rôle in these processes. The type of logic that emerges is not Boolean, confirming and extending earlier findings on the logic of schizophrenia.

The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia

Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes export of selected cargo proteins from the trans-Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4. AP4E1- knock-out (KO) HeLa cells and hippocampal neurons from Ap4e1-KO mice display increased co-localization of ApoER2 with Golgi markers. Furthermore, hippocampal neurons from Ap4e1-KO mice and AP4M1-KO human iPSC-derived cortical i3Neurons exhibit reduced ApoER2 protein expression. Analyses of biosynthetic transport of ApoER2 reveal differential post-Golgi trafficking of the receptor, with lower axonal distribution in KO compared to wild-type neurons, indicating a role of AP-4 and the ISSF/Y motif in the axonal localization of ApoER2. Finally, analyses of Reelin signaling in mouse hippocampal and human cortical KO neurons show that AP4 deficiency causes no changes in Reelin-dependent activation of the AKT pathway and only mild changes in Reelin-induced dendritic arborization, but reduces Reelin-induced ERK phosphorylation, CREB activation, and Golgi deployment. This work thus establishes ApoER2 as a novel cargo of the AP-4 complex, suggesting that defects in the trafficking of this receptor and in the Reelin signaling pathway could contribute to the pathogenesis of HSP caused by mutations in AP-4 subunits.

Sequence-Structure Analysis Unlocking the Potential Functional Application of the Local 3D Motifs of Plant-Derived Diterpene Synthases.

Plant-derived diterpene synthases (PdiTPSs) play a critical role in the formation of structurally and functionally diverse diterpenoids. However, the specificity or functional-related features of PdiTPSs are not well understood. For a more profound insight, we collected, constructed, and curated 199 functionally characterized PdiTPSs and their corresponding 3D structures. The complex correlations among their sequences, domains, structures, and corresponding products were comprehensively analyzed. Ultimately, our focus narrowed to the geometric arrangement of local structures. We found that local structural alignment can rapidly localize product-specific residues that have been validated by mutagenesis experiments. Based on the 3D motifs derived from the residues around the substrate, we successfully searched diterpene synthases (diTPSs) from the predicted terpene synthases and newly characterized PdiTPSs, suggesting that the identified 3D motifs can serve as distinctive signatures in diTPSs (I and II class). Local structural analysis revealed the PdiTPSs with more conserved amino acid residues show features unique to class I and class II, whereas those with fewer conserved amino acid residues typically exhibit product diversity and specificity. These results provide an attractive method for discovering novel or functionally equivalent enzymes and probing the product specificity in cases where enzyme characterization is limited.

Concurrent prediction of RNA secondary structures with pseudoknots and local 3D motifs in an integer programming framework.

The prediction of RNA structure canonical base pairs from a single sequence, especially pseudoknotted ones, remains challenging in a thermodynamic models that approximates the energy of the local 3D motifs joining canonical stems. It has become more and more apparent in recent years that the structural motifs in the loops, composed of noncanonical interactions, are essential for the final shape of the molecule enabling its multiple functions. Our capacity to predict accurate 3D structures is also limited when it comes to the organization of the large intricate network of interactions that form inside those loops. We previously developed the integer programming framework RNA Motifs over Integer Programming (RNAMoIP) to reconcile RNA secondary structure and local 3D motif information available in databases. We further develop our model to now simultaneously predict the canonical base pairs (with pseudoknots) from base pair probability matrices with or without alignment. We benchmarked our new method over the all nonredundant RNAs below 150 nucleotides. We show that the joined prediction of canonical base pairs structure and local conserved motifs (i) improves the ratio of well-predicted interactions in the secondary structure, (ii) predicts well canonical and Wobble pairs at the location where motifs are inserted, (iii) is greatly improved with evolutionary information, and (iv) noncanonical motifs at kink-turn locations. The source code of the framework is available at https://gitlab.info.uqam.ca/cbe/RNAMoIP and an interactive web server at https://rnamoip.cbe.uqam.ca/.

Learning Creative Economy Empowerment through Optimizing Media Digital and Utilizing Inorganic Waste to Become Batik Patterned Chairs

The aim of this assistance is to provide learning of training and assistance in optimizing digital marketing media through social media, such as Instagram, websites and Facebook. The second is to provide training and assistance in utilizing inorganic waste to make chairs with local batik motifs in Indonesia, training and assistance in introducing local batik in Indonesia as a brand in promoting batik patterned chair products. The method used Asset Based Community Development (ABCD) by maximizing asset potential. The results of this mitigation have achieved the target, that refers to low and medium hanging fruit, the subject of mitigation is the Waste Bank Community and Members of Pagar Nusa Metro City, the Waste Bank Community and the surrounding community have understood the condition of Smapah in Metro City and the risks or impacts arising from the pile up. Garbage is increasingly piling up in Metro City. The second is the reducing subject to understand theoretically and practically how to use inorganic waste such as aqua bottles, cloth, plastic into sofas or chairs with batik motifs. The third target is that Instagram business account owners can optimize and utilize digital media, such as Instagram as a one of the platforms for online digital marketing. At this stage, business Instagram users or marketing subjects understand how to optimize various features on Instagram and strategies for using those features, such as optimizing business Instagram profiles, determining posting schedules, optimizing hashtags, creating interesting content, creating contact and email buttons, or website, Optimizing Insights and Instagram stories, Optimizing Ads or Advertisements on Instagram.
 Keywords: Optimizing Media Digital, Utilizing Inorganic Waste, Learning Creative Economy

Local Plant Motif of Kain Suket Ajang

This study delves into the identity of Suket Ajang, a traditional craft in Sarawak, particularly among Rajang's Melanau population. Employing semiotics, the research deciphers the complex meanings and cultural nuances embedded in Suket Ajang's native plant motifs. Through an in-depth examination of literary and visual materials, the study unveils the symbolic language within Suket Ajang, showcasing how individual motifs are chosen, investigated, and classified based on their semiotic qualities. This method sheds light on the aesthetic and semiotic elements, revealing the intricate blend of local plant features. Notable motifs like buwak tulau and tapok pedadah further contribute to Suket Ajang's rich cultural identity.

Signal-regulated Unmasking of Nuclear Localization Motif in the PAS Domain Regulates the Nuclear Translocation of PASK

The ligand-regulated PAS domains are one of the most diverse signal-integrating domains found in proteins from prokaryotes to humans. By biochemically connecting cellular processes with their environment, PAS domains facilitate an appropriate cellular response. PAS domain-containing Kinase (PASK) is an evolutionarily conserved protein kinase that plays important signaling roles in mammalian stem cells to establish stem cell fate. We have shown that the nuclear translocation of PASK is stimulated by differentiation signaling cues in muscle stem cells. However, the mechanistic basis of the regulation of PASK nucleo-cytoplasmic translocation remains unknown. Here, we show that the PAS-A domain of PASK contains a putative monopartite nuclear localization sequence (NLS) motif. This NLS is inhibited in cells through intramolecular association with a short linear motif, termed the PAS Interacting Motif (PIM), found upstream of the kinase domain. This interaction serves to retain PASK in the cytosol in the absence of signaling cues. Consistent with that, we show that metabolic inputs induce PASK nuclear import, likely by disrupting this association. We suggest that a route for such linkage may occur through the PAS-A ligand binding cavity. We show that PIM recruitment and artificial ligand binding to the PAS-A domain occur at neighboring locations that could facilitate metabolic control of the PAS-PIM interaction. Thus, the intramolecular interaction in PASK integrates metabolic signaling cues for nuclear translocation and could be targeted to control the balance between self-renewal and differentiation in stem cells.