Search Results (85)

The crystal structures of naphthalene dicarboxamides, namely 1,4-naphthalene dicarboxamide (1,4-NDA), 2,6-naphthalene dicarboxamide (2,6-NDA), and 2,7-naphthalene dicarboxamide (2,7-NDA), are presented for the first time, along with an analysis of their supramolecular organization. The compounds, obtained in single-crystalline form via solvothermal crystallization from methanol, are stable in air to near 350 °C and have melting points above 300 °C. In their densely packed structures (ρ = 1.43–1.47 cm³g⁻¹) the combination of ${\mathrm{C}}_1^1$ (4) chains and ${\mathrm{R}}_2^2$(8) rings generates one-dimensional hydrogen-bonded ladders, with an additional ${\mathrm{R}}_4^2$(8) pattern. The amide groups and the naphthalene rings form dihedral angles between 22° and 40°. Neighboring H-bond ladders run parallel in 1,4-NDA and 2,6-NDA and are connected by means of the naphthalenedyil cores so that two-dimensional (2D) H-bonded sheets are obtained. Except for a weak intra-sheet π–π stacking in 1,4-NDA, there are no π–π stacking and C–H⋯π interactions. The ${\mathrm{R}}_2^2$(8) rings act as four-connected nodes, leading to the formation of two-dimensional H-bonded planar sheets with sql topology for the nearly linear dicarboxamides 1,4-NDA and 2,6-NDA and cds topology for the angular 2,7-NDA. Hirshfeld surface analysis and NCI plots provide additional insight into the H-bonding interactions. Full article

We report the topochemical solid-state polymerization of different series of symmetrical diacetylenes (DAs) and asymmetrical chlorodiacetylenes (ClDAs), whose members differ in their alkyl spacing lengths of one to four methylene units (n = 1, 2, 3, 4) between the diyne and carbamate functionalities. Structure determination by single-crystal X-Ray diffraction (SCXRD) confirms that in each of these series, at least 50% of the analyses show monomers with a particular stacking pattern presenting two potential directions of polymerization simultaneously. An organization of a crystalline polydiacetylene (PDA) with an oblique chain orientation with respect to the network of cooperatives hydrogen bonds is rather rare in the literature (only two cases), and here we have obtained two more examples of this type of structural motif (supported by SCXRD analysis of the polymer). Orientation control is essential to optimize the performance of conjugated polymers, and a spacer length modification strategy presents a potential way to achieve this in the case of PDA. Full article

The legend of the old man Simeon, who received Jesus in his arms and was one of the Septuagint translators, is almost unknown in Western Christianity but is very popular today among Orthodox Christians. The version circulating in Orthodox churches is based on the account in Demetrius of Rostov’s Lives of the Saints. The article explores the occurrences of the legend in modern, medieval Slavonic, Byzantine, and oriental writings and attempts to identify the stages of the transmission of the legend from antiquity to modern times. The historical analysis and the comparison of the motifs found in these writings make the hypothesis of a Byzantine archetype of the legend plausible. This writing has been lost, but it was previously translated into Syriac, Arabic, and Slavonic, contributing to the spread of the legend in Eastern and Slavic Christianity. The legend builds on the identification of Simeon in Luke’s Gospel with Shimʿon ha-Tsaddiq. It interprets Luke 2:26 by constructing a pre-history of the episode that places Simeon into the time of the Septuagint translation. The miracle of prolonging Righteous Simeon’s life functions as a reconfirmation of the fundamental character of Isaiah 7:14 for Christianity. Full article

In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena can occur in blood from individuals with circulating inflammatory molecules (and also some originating from viruses and bacteria). Such pathological clotting can result in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We thus provide evidence against such a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant quantitative overlap with the normal plasma proteome and no correlation between plasma protein abundance and their presence in fibrinaloid microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand factor are well represented. Using bioinformatic tools, including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots’ resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders. Full article

β-amyloid (Aβ) peptides form self-organizing fibrils in Alzheimer’s disease. The biologically active, toxic Aβ25–35 fragment of the full-length Aβ-peptide forms a stable, oriented filament network on the mica surface with an epitaxial mechanism at the timescale of seconds. While many of the structural and dynamic features of the oriented Aβ25–35 fibrils have been investigated before, the β-strand arrangement of the fibrils and their exact orientation with respect to the mica lattice remained unknown. By using high-resolution atomic force microscopy, here, we show that the Aβ25–35 fibrils are oriented along the long diagonal of the oxygen hexagon of mica. To test the structure and stability of the oriented fibrils further, we carried out molecular dynamics simulations on model β-sheets. The models included the mica surface and a single fibril motif built from β-strands. We show that a sheet with parallel β-strands binds to the mica surface with its positively charged groups, but the C-terminals of the strands orient upward. In contrast, the model with antiparallel strands preserves its parallel orientation with the surface in the molecular dynamics simulation, suggesting that this model describes the first β-sheet layer of the mica-bound Aβ25–35 fibrils well. These results pave the way toward nanotechnological construction and applications for the designed amyloid peptides. Full article

This paper examines the writings of European travelers, chaplains, and resident doctors on pandemics in the Mediterranean regions from the 16th to the 19th centuries. Using French comparative literary theory, the article highlights how Muslim communities in Egypt, Turkey, Aleppo, and Mecca were stereotyped based on their belief in predestination, their failure to avoid contamination, and their lack of social distancing during plague outbreaks. This paper argues that travelers were influenced by Renaissance humanism, Ars Apodemia, religious discourses, and texts, such as plague tracts, model town concepts, the book of orders, and tales, and that they essentialized Mediterranean Islamicate societies by depicting contamination motifs supposedly shaped by the absence of contagion theory in prophetic medicines. Regarding plague science, this paper concludes that Christian and Muslim intellectuals had similar approaches until the Black Death and that Arabs were eclectic since the Abbasid period. This paper further maintains that the travelers’ approaches fostered chauvinism and the cultural hegemony of the West over the Orient since the Renaissance and Enlightenment periods, driven by eschatology, conversion, and power structure narratives. Full article

Acquiring meaningful representations of gene expression is essential for the accurate prediction of downstream regulatory tasks, such as identifying promoters and transcription factor binding sites. However, the current dependency on supervised learning, constrained by the limited availability of labeled genomic data, impedes the ability to develop robust predictive models with broad generalization capabilities. In response, recent advancements have pivoted towards the application of self-supervised training for DNA sequence modeling, enabling the adaptation of pre-trained genomic representations to a variety of downstream tasks. Departing from the straightforward application of masked language learning techniques to DNA sequences, approaches such as MoDNA enrich genome language modeling with prior biological knowledge. In this study, we advance DNA language models by utilizing the Motif-oriented DNA (MoDNA) pre-training framework, which is established for self-supervised learning at the pre-training stage and is flexible enough for application across different downstream tasks. MoDNA distinguishes itself by efficiently learning semantic-level genomic representations from an extensive corpus of unlabeled genome data, offering a significant improvement in computational efficiency over previous approaches. The framework is pre-trained on a comprehensive human genome dataset and fine-tuned for targeted downstream tasks. Our enhanced analysis and evaluation in promoter prediction and transcription factor binding site prediction have further validated MoDNA’s exceptional capabilities, emphasizing its contribution to advancements in genomic predictive modeling. Full article

Natural products (NPs) have diverse biological activity and significant medicinal value. The structural diversity of NPs is the mainstay of drug discovery. Expanding the chemical space of NPs is an urgent need. Inspired by the concept of fragment-assembled pseudo-natural products, we developed a computational tool called NIMO, which is based on the transformer neural network model. NIMO employs two tailor-made motif extraction methods to map a molecular graph into a semantic motif sequence. All these generated motif sequences are used to train our molecular generative models. Various NIMO models were trained under different task scenarios by recognizing syntactic patterns and structure–property relationships. We further explored the performance of NIMO in structure-guided, activity-oriented, and pocket-based molecule generation tasks. Our results show that NIMO had excellent performance for molecule generation from scratch and structure optimization from a scaffold. Full article

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif is found next to another ill-defined cysteine that we show is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCMs) suggests a candidate Fe-S cluster ligand role. Hence, we generated, by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo. Full article

This article examines motifs of falling, recoiling, and turning across Chester Himes’ oeuvre as figurations of Black susceptibility to racial violence. These images reference and reconstruct an event from Himes’ early adulthood: his catastrophic fall down an elevator shaft. Taking a psychoanalytically oriented approach, I analyze the metonymic connections between these motifs, rather than reading them in their chronological order, using Jean Laplanche’s theory of après-coup. I argue that the recursive quality of these images in Himes’ work is not merely an unconscious repetition or conscious working through of a traumatic biographical event but part of an endeavor to imagine different ways to inhabit and survive the structural trauma of Jim Crow America. Full article

While some Inka structures and motifs align with astronomical and horizon markers, a significant portion of their constructions exhibit different patterns. We examined the potential correlation between the orientation patterns of the Inka walls and Andean geomorphology, aiming to uncover the extent to which the physical landscape guided these ancient architectural design methodologies. Using geospatial technology and specially developed peak detection and recognition software, we extensively and meticulously analyzed over 40,000 m of surveyed Inka walls and 20,000 mountain peaks across 11 distinct geographical areas. The analysis revealed a significant correlation between key wall orientations and the parallel peak alignment of the Andean Mountain Range. This suggests a purposeful encoding of landscape orientations into Inka architecture. These findings propose a novel perspective on the intricate relationship between Inka culture and the Andean highlands’ topography. Furthermore, this research introduces a distinctive methodological approach to exploring the impact of natural landscapes on architectural planning, establishing a foundation for comparative studies among other ancient civilizations. Full article

Sugar transporters play important roles in plant growth and development, flowering and fruiting, as well as responses to adverse abiotic and biotic environmental conditions. Lilies (Lilium spp.) are some of the most representative ornamental bulbous flowers. Sugar metabolism is critical for bulb formation in lilies; therefore, clarifying the amount and expression pattern of sugar transporters is essential for further analyzing their roles in bulb formation. In this study, based on the transcriptome data of the Lilium Oriental hybrid ‘Sorbonne’ and Lilium × formolongi, a total of 69 and 41 sugar transporters were identified in ‘Sorbonne’ and Lilium × formolongi, respectively, by performing bioinformatics analysis. Through phylogenetic analysis, monosaccharide transporters (MSTs) can be divided into seven subfamilies, sucrose transporters (SUTs) can be divided into three subgroups, and sugars will eventually be exported transporters (SWEETs) can be divided into four clades. According to an analysis of conserved motifs, 20, 14, and 12 conserved motifs were predicted in MSTs, SUTs, and SWEETs, respectively. A conserved domain analysis showed that MSTs and SUTs contained a single domain, whereas most of the SWEETs harbored two MtN3/saliva domains, also known as a PQ-loop repeat. The LohINT1, which was predicted to have a smaller number of transmembrane structural domains, was cloned and analyzed for subcellular localization. It was found that the LohINT1 protein is mainly localized in the cell membrane. In addition, the expression analysis indicated that 22 LohMSTs, 1 LohSUTs, and 5 LohSWEETs were upregulated in ‘Sorbonne’ 1 day after scale detachment treatment, suggesting that they may regulate the initiation of the bulblet. A total of 10 LflMSTs, 1 LflSUTs, and 6 LflSWEETs were upregulated 4~6 months after sowing, which corresponds to the juvenile-to-adult transition phase of Lilium × formolongi, suggesting that they may also play a role in the accompanying bulb swelling process. Combined with quantitative real-time PCR (qRT-PCR) analysis, LohSTP8 and LohSTP12 were significantly overexpressed during the extremely early stage of bulblet initiation, and LflERD6.3 was significantly overexpressed during the growth of the underground bulblet, suggesting that they may be key sugar transporters in the formation of lily bulbs, which needs further functional verification. Full article

The multifunctional linker molecules are crucial for the bio-orthogonal reaction for proteomic target profiling. Herein, we wish to present a novel type of biotin-based tetra-functional bio-orthogonal linkers 3a–3h named BPPA which, possessing a unique photolabile phenacyl ester motif, were readily prepared in 85–90% yields by a simple and green one-step protocol from commercially available and inexpensive reagents of biotin acids and 4’-ethynyl/azido 2-bromoacetophenones. The typical click reaction of BPPA linkers 3a and 3e via copper-catalyzed azide–alkyne cycloaddition (CuAAC) took place easily, resulting in the corresponding BPPA-triazole adducts 4a and 4b in nearly quantitative yields. A further cleavability evaluation of 4a and 4b demonstrated that the expected C-O bond detachment could be accomplished efficiently and rapidly by UV irradiation or by ammonia hydrolysis, respectively, resulting in the residual (hydroxyl)acetylphenyl triazole fragment supposed to be attached to proteins during biological manipulations. The BPPA linkers, with dual clickable options of either the terminal azide or alkyne clickable group, exhibit high potentials for various CuAAC-oriented bio-orthogonal reactions. Full article

Mannich bases are a class of organic compounds usually obtained by the condensation reaction between an amine, a compound with active hydrogens, and an aldehyde. They are versatile intermediates in organic synthesis, and those compounds containing this motif find applications in pharmaceutical, agrochemical, and even material fields since they are widely known for their wide range of biological activities, including antimicrobial properties. Thus, as part of our interest in antifungal agents, this narrative review aimed to gather information from the literature on the synthesis of various representative Mannich-base-containing compounds, particularly centered on those exhibiting antifungal properties. In this context, the compilation indicated that Mannich bases could be considered as a relevant toxophore/pharmacophore by incorporating heterocyclic moieties to be implemented for the design of new antifungal agents, given its proven efficacy against phytopathogens, other opportunistic human pathogens, and some dermatophytic fungal species, which can be further exploited as agrochemical agents or in medicinal applications to treat fungal infections. The antifungal effect exhibited by Mannich bases conjugated with oxa and/or aza-heterocycles suggests that compounds that have a heterocyclic system attached to the β-amino core are attractive alternatives oriented to the synthesis of novel and helpful antifungal agents. Full article

An appreciation of the emphasis on flexibility in the Analects is one of the most consistent motifs in the various interpretations of this text. When applied specifically to normative readings, embracing adaptability, having malleable standards, and taking particulars into account are both promising and challenging ways to think about whether something might be moral or ethical. This paper attempts to deconstruct this familiar discussion along novel lines that can reveal new ways to reflect on the importance of flexibility in the Analects, while, at the same time, it reconstrues ways in which comparative projects might be oriented. The main argument is this: the Analects does not recognize a categorical distinction between a moral and non-moral realm. Whereas, in much modern academic thought, there is a distinction between what counts as contingencies and what is up to the individual, which, in turn, loosely corresponds to the non-moral and moral realms, the Analects does not make such clear distinctions. Everything, including core moral issues such as the individual’s own choice, moral guidelines, and the contextualization of (moral) models, is all ultimately grounded in contingencies. Nevertheless, the Analects provides ways of reflecting on choices and actions that aim to steer people in specific directions. We may understand this as a type of morality, but one that is significantly distinct from those wherein the difference between the moral (non-contingent) and non-moral (contingent) is foundational. Full article