Search Results (741)

Circadian rhythms are endogenous ~24 h oscillations that regulate diverse biochemical processes. Although stress responses can exhibit circadian modulation, evidence for rhythmic regulation of stress granules (SGs)—cytoplasmic RNA–protein condensates formed under stress—remains limited. We investigated sodium arsenite-induced SG dynamics in NIH/3T3 cultures. SG number, eIF3 signal intensity—an established SG marker—and area oscillated with a period of ~24 h. These rhythms persisted in Bmal1^−/− mouse embryonic fibroblasts (MEFs), despite lacking a transcription–translation feedback loop (TTFL) that constitutes the canonical circadian clock, but with altered amplitude and phase, indicating partial dependence on the molecular clock. Several SG-associated RNA-binding proteins (TIA-1, BRF1, hnRNP Q, and LARK) exhibited time-dependent changes at the mRNA and/or protein level, suggesting potential mechanisms for rhythmic SG modulation. Unlike previous in vivo reports linking SG variation to eIF2α phosphorylation, no temporal changes in phosphorylated eIF2α were observed, highlighting differences between isolated cells and tissues. Our results show that SG rhythmicity can persist without BMAL1, supporting alternative oscillatory mechanisms that contribute to the temporal organization of stress responses. Given their role in cell survival and the association of SG dysfunction with disease, these rhythms provide insight into how cellular stress responses are temporally regulated. Full article

For centuries, artisans have resolved intricate engineering conundrums with intuitive ingenuity, bequeathing a legacy of design wisdom that remains largely untapped in contemporary biomimetics. This “anthro-creative” form of biomimicry, deeply embedded within traditional crafts such as Chaozhou woodcarving, is predominantly tacit and qualitative, which has traditionally eluded systematic interpretation. To address this, we propose the Hierarchical Biomimetics-Based Evaluation System (HBBES), a transdisciplinary framework that couples expert-defined hierarchies through the Analytic Hierarchy Process (AHP) with perceptual assessments from one hundred public evaluators via Fuzzy Comprehensive Evaluation (FCE). Applied to canonical works—including the Lobster and Crab Basket (overall score: 4.36/5.00)—the HBBES revealed a striking finding: both expert and public valuations are anchored not in structural hierarchy, but in aesthetic resonance, particularly the craft’s lifelike morphological analogy and nuanced modulation of light. Beyond offering a replicable pathway for translating artisanal intuition into operative design principles, this study proposes a culture-driven paradigm for biomimetics, bridging intangible heritage with technological innovation. Full article

The Landau–de Gennes model is one of the most significant fundamental frameworks in The Physics of Liquid Crystals and Soft Matter Physics. It is validated by the universal parameterisation of the Cotton–Mouton effect, the Kerr effect, and light scattering in the isotropic phase of nematogens. However, as early as 1974, de Gennes identified the first two puzzling problems of this model. Over the following decades, this list has expanded. This report presents the first comprehensive analysis of these issues, with the explicit experimental reference. It focuses on the hardly coherently discussed pretransitional changes in the dielectric constant and the extension in a strong electric field, specifically the nonlinear dielectric effect (NDE). Notably, there are uniquely different pretransitional forms of pretransitional effects, depending on molecular structural features such as permanent dipole moment loci or a steric hindrance. It is tested for 5CB, 5*CB, and MBBA: nematogenic liquid crystalline materials that differ in the above features. The obtained specific pretransitional effects and the evidence for the essential importance of the interplay between observation and pretransition fluctuations time scales led to a new coherent, model-based explanation of all the discussed problems, which cannot be explained within the canonical Landau–de Gennes model. Full article

Retinoic acid (RA) binds RA (RAR) and Retinoid X (RXR) receptors to elicit biological effects by regulating transcription. RA is also known to have non-canonical activities mediated, primarily, by cellular retinoic acid-binding protein 1 (CRABP1) which forms protein complexes named “CRABP1 signalosomes” to regulate cytosolic signaling independent of RARs/RXRs. This review focuses on therapeutic applications in neurodegeneration by targeting CRABP1 signalosomes including CRABP1–MAPK, CRABP1–CaMKII, CRABP1–eIF2α, and others recently identified from our proteomic studies. The mouse Crabp1 gene is regulated by various epigenetic factors and is important for the health of multiple cell types including motor neurons (MNs). In humans, CRABP1 gene expression is reduced in ALS- and SMA-patient MNs. RA is a therapeutic agent for leukemias and dermatological disorders and is being investigated for managing neurodegenerative diseases, but its therapeutic effects are accompanied by RAR-mediated toxic effects. We have uncovered a novel class of synthetic retinoids that bind CRABP1 without acting on RARs, circumventing RAR-mediated toxic effects. These first-generation CRABP1-selective compounds C3, C4, and C32 target CRABP1–MAPK and/or CRABP1–CaMKII signalosomes. This knowledge, together with emerging structural information, sheds lights on the strategies in designing next-generation CRABP1-signalosome-selective retinoids for the management of neurodegenerative diseases. Full article

This essay expands the canon of sources for liberative theologies by examining the artwork of leading Caribbean muralist Sir Dunstan St. Omer. In conjunction with his close friend—Nobel Laureate Sir Derek Walcott—St. Omer pioneered a form of artistic expression which he used to great and imaginative effect as counter-narrative to dehumanizing colonial myth. The essay presents two of the artist’s best-known murals, discusses their significance in the arc of Caribbean religiosity, and extrapolates critical insight for a contemporary Black Catholic mysticism. Full article

Vincristine is a classical chemotherapeutic agent widely used for its ability to disrupt microtubule polymerization, yet additional molecular effects may contribute to its anticancer activity. G-quadruplexes (G4s), non-canonical nucleic acid structures enriched in regulatory regions of the genome and in mitochondrial DNA, have emerged as relevant modulators of cellular homeostasis. In this study, we investigated whether vincristine can influence G4 biology. Cancer cells treated with vincristine were analyzed by immunofluorescence, revealing a consistent increase in nuclear and mitochondrial G4 foci. In particular, mitochondrial G4s were significantly elevated by approximately 1.5–2.5 fold compared to untreated cells, an effect accompanied by a detectable reduction in membrane potential, indicative of impaired organelle function. In addition, biophysical analyses on representative G4-forming sequences were carried out. Proton nuclear magnetic resonance titrations showed localized chemical shift perturbations upon vincristine addition, circular dichroism confirmed preservation of G4 topology, and isothermal titration calorimetry indicated weak but enthalpically favorable interactions. Taken together, these results suggest that vincristine perturbs both the cellular G4 landscape and mitochondrial homeostasis, while also engaging G4 DNA in vitro. Although additional studies are required to establish the mechanistic details, this work provides proof-of-concept for a previously unrecognized dimension of vincristine’s anticancer action. Full article

The Ōbaku Edition of the Buddhist Canon, initiated and spearheaded by Tetsugen Dōkō (鐵眼道光 1630–1682), profoundly influenced Japanese Buddhism and printing culture. Although the Ōbaku Edition has long been recognized as a product of cross-border collaboration, earlier studies have primarily focused on its textual features and religious significance after publication. As a result, the specific mechanisms and significance of its transnational nature have remained underexplored. This study revisits the canon’s compilation as a complex trans-sectarian and transnational social practice. Drawing on a variety of sources, it provides new insights into the production of the Ōbaku Canon, showing that this trans-sectarian project was driven by the interplay of several key dynamics: transnational networks supplying its base text, intellectual contributions from Chinese migrants, local social needs in post-fire Nagasaki, and Tetsugen’s personal aim to use the canon in doctrinal debate. Tetsugen’s printing endeavor continued the medieval tradition of kanjin (fundraising), serving as a religious, educational, and institutional undertaking shaped by interactions with broader socio-economic support. Positioned within a wider social framework, Tetsugen’s cross-sectarian activities facilitated the successful circulation and popularization of the canon, promoting a shift in the use of Buddhist scriptures from prayer-centered practice to doctrinal study and reflecting a broader transformation in Japanese Buddhism, from state-supported Buddhism to more popular forms. Full article

DROSHA protein is widely known for its essential role in the microRNA (miRNA/miR) biogenesis pathway where, together with its co-factor DGCR8, it forms the “Microprocessor” complex and catalyzes the primary miRNA (pri-miRNA) processing in the nucleus. Nevertheless, DROSHA also seems to participate in several miRNA-independent cellular mechanisms, such as transcriptional regulation, RNA processing and genome integrity maintenance. Hence, the present study aims to further investigate novel miRNA-independent activities of DROSHA protein, with potentially regulatory roles in the oncogenesis of human cancer cells. Our results reveal a new, strong profile of microprocessor-independent DROSHA localization at the Golgi apparatus in several human cancer cell lines of different tissue origin, with hepatic carcinoma, thyroid cancer, urothelial bladder cancer, colon carcinoma and melanoma being the cellular model systems herein examined. Notably, oncogenic activity, malignancy grade and metastatic capacity are shown to be strongly associated with DROSHA’s compartmentalization at Golgi, a phenotype that does not seem to rely on p53 protein’s functionality. Taken together, through employment of advanced confocal laser scanning microscopy (CLSM) and molecular modeling, we herein unveil the ability of DROSHA, but not AGO2 and DICER, to reside at Golgi, where DROSHA can physically interact with the GM130 Golgi-specific component, thus indicating DROSHA’s engagement in non-canonical and miRNA-independent—but also Golgi apparatus-dependent—novel mechanisms that can be tightly coupled with malignancy dynamics and beneficially utilized as potential biomarkers and therapeutic targets for human cancer. Full article

A rigorous framework for determining actual and minimum boil-up ratios in binary distillation combining analytical mass and energy balances with an extended Ponchon–Savarit graphical approach was implemented. First, global balances across the enriching and stripping sections yield a closed-form expression of the boil-up ratio (V_B) based on enthalpy differences. Second, the V_B was directly determined from an enthalpy–composition diagram by measuring the enthalpy segments between the saturated liquid, vapor, and heat-duty points. Applying this method to high-stage columns confirms that the two methods converge on identical V_B values. Based on these findings, a unified graphical methodology was developed to determine the minimum boil-up ratio (V_Bmin). V_Bmin can be determined on the same diagram by locating the intersections of the extremal tie lines in both the enriching and exhausting sections, analogous to the reflux-pinch points. This procedure was systematically validated across the five canonical feed thermal states. The implemented method is a graphical approach based on the Ponchon–Savarit technique, developed for binary systems. Full article

The classification of exact solutions of Maxwell vacuum equations for pseudo-Riemannian spaces with spatial symmetry (homogeneous non-null spaces in Petrov) in the presence of electromagnetic fields invariant with respect to the action of the group of space motions is summarized. A new classification method is used, common to all homogeneous zero spaces of Petrov. The method is based on the use of canonical reper vectors and on the use of a new approach to the systematization of solutions. The classification results are presented in a form more convenient for further use. Using the previously made refinement of the classification of Petrov spaces, the classification of exact solutions of Maxwell vacuum equations for spaces with the group of motions $G_3\left(VIII\right)$ is completed. Full article

This study dives into the interactive functions of the palm-up across four language ecologies drawing on comparable corpus data from American Sign Language (ASL)-American English and French Belgian Sign Language (LSFB)-Belgian French. While researchers have examined palm-up in many different spoken and signed language contexts, they have primarily focused on the canonical forms and its epistemic variants. Work that directly compares palm-up across modalities and language ecologies remains scarce. This study addresses such gaps by documenting all instances of the palm approaching supination in four language ecologies to analyze its interactive functions cross-linguistically and cross-modally. Capitalizing on an existing typology of interactive gestures, palm-up annotations were conducted using ELAN on a total sample of 48 participants interacting face-to-face in dyads. Findings highlight the multifunctional nature of palm-up in terms of conversational dynamics with cross-modal differences in the specific interactive use of palm-up between spoken and signed language contexts. These findings underscore the versatility of the palm-up and reinforce its role in conversational dynamics as not merely supplementary but integral to human interaction. Full article

Topoisomerase 1 (Top1) removes transcription-related helical torsions and thus plays an important role in preventing genome instability instigated by the formation of non-canonical DNA secondary structures. The genetically tractable Saccharomyces cerevisiae model proved effective in defining the critical function of Top1 to prevent recombination and chromosomal rearrangement at G4-forming genomic loci and studying the human cancer-associated Top1 mutants through the expression of analogous yeast mutants. We previously showed that cleavage-defective Top1 mutants strongly elevate the rate of recombination at G4 DNA, which involves binding to G4 DNA and interaction with the protein nucleolin (Nsr1 in yeast). Here, we further explored the mechanism of genome instability induced by the yeast Top1Y740* mutant, analogous to the human Top1W765Stop mutant conferring resistance to CPT. We show that yTop1Y740* elevates duplications as well as recombination specifically at G4-forming sequences. Interestingly, SUMOylation of yTop1Y740*, which does not affect the G4 DNA-binding or Nsr1-interaction by this mutant, is necessary for such elevated G4-specific genome instability. Many tumors with mutations at the C-terminal residues of Top1, particularly W765, have significantly high G4-associated mutations, underscoring the importance of further investigation into how SUMOylation affects the function of these Top1 mutants at G4 DNA. Full article

Flow past bluff bodies (e.g., circular cylinders) forms a canonical context for teaching external flow separation, vortex shedding, and the coupling between surface pressure and hydrodynamic forces in offshore engineering. Conventional laboratory implementations, however, often fragment local and global measurements, delay data feedback, and omit intelligent modeling components, thereby limiting the development of higher-order cognitive skills and data literacy. We present a low-cost, modular, data-enabled instructional hydrodynamics platform that integrates a transparent recirculating water channel, multi-point synchronous circumferential pressure measurements, global force acquisition, and an artificial neural network (ANN) surrogate. Using feature vectors composed of Reynolds number, angle of attack, and submergence depth, we train a lightweight AI model for rapid prediction of drag and lift coefficients, closing a loop of measurement, prediction, deviation diagnosis, and feature refinement. In the subcritical Reynolds regime, the measured circumferential pressure distribution for a circular cylinder and the drag and lift coefficients for a rectangular cylinder agree with empirical correlations and published benchmarks. The ANN surrogate attains a mean absolute percentage error of approximately 4% for both drag and lift coefficients, indicating stable, physically interpretable performance under limited feature inputs. This platform will facilitate students’ cross-domain transfer spanning flow physics mechanisms, signal processing, feature engineering, and model evaluation, thereby enhancing inquiry-driven and critical analytical competencies. Key contributions include the following: (i) a synchronized local pressure and global force dataset architecture; (ii) embedding a physics-interpretable lightweight ANN surrogate in a foundational hydrodynamics experiment; and (iii) an error-tracking, iteration-oriented instructional workflow. The platform provides a replicable pathway for transitioning offshore hydrodynamics laboratories toward an integrated intelligence-plus-data literacy paradigm and establishes a foundation for future extensions to higher Reynolds numbers, multiple body geometries, and physics-constrained neural networks. Full article

We explore a timeless approach to quantum theory, in the form of the Page–Wootters mechanism, in which a gravitational interaction is introduced between the system and a finite-dimensional clock. The clock model used is the recently proposed quasi-ideal clock, a construction that can approximate the time–energy canonical commutation relation. We derive equations of motion for the case in which the system is in a pure and mixed state, obtaining a Schrödinger-like equation that leads to a non-linear equation exhibiting decoherence due to the non-ideal nature of the clock and gravitational coupling. A distinctive feature of this equation is that it exhibits dependence on the system’s initial conditions. Full article

Background/Objectives: Previous research has demonstrated that the initial letters of a word likely play a privileged role in visual word recognition, such that reading and visual recognition errors reflecting changes in this position are much less likely. For example, prior case studies of attentional dyslexia reported that participants were most accurate at rejecting nonwords formed by transposing a word’s first two letters (e.g., WONER from OWNER) compared to transpositions in later positions. The current study aimed to replicate and extend this finding in patients with posterior cortical atrophy (PCA), a neurodegenerative condition associated with visuospatial and attentional impairments. Methods: Two PCA patients completed lexical decision tasks involving five-letter real words and nonwords created either by transposing adjacent letters (in positions 1 + 2, 2 + 3, 3 + 4, or 4 + 5) or using matched nonword controls. To assess robustness, tasks were repeated across test–retest sessions. Stimuli were presented in both canonical horizontal and non-canonical vertical (marquee) formats. Accuracy, response bias, and sensitivity (d′) were estimated, with 95% confidence intervals derived from a nonparametric bootstrap procedure. Within-case logistic regressions were also conducted to illustrate the findings. Results: Both patients showed significantly higher accuracy and lower response bias for 1 + 2 transposition nonwords relative to other positions. This early-letter advantage persisted across test–retest observations and was maintained when words were presented in the vertical format, suggesting orientation-invariant effects. The bootstrap and regression analyses provided convergent support for these results. Conclusions: The findings provide novel evidence in PCA that the encoding of early letter positions operates independently of visual orientation and persists despite attentional deficits. This supports models in which the initial letters serve as a key anchor point in orthographic processing, highlighting the privileged and resilient status of early letter encoding in visual word recognition. Full article