bluuebunny/crossref_metadata_2025 huggingface dataset:
Cleavage of MALAT1 RNA by 14-nt sgRNA-guided tRNase ZL
Authors: Takahashi Masayuki , Nashimoto Masayuki
Published: January 2025

We have been developing a gene suppression technology, tRNase ZL-utilizing efficacious (TRUE) gene silencing, in which artificially designed small guide RNA (sgRNA) guides tRNase ZLto cleave cellular target RNA. In this study, we examined 14-nt linear-type sgRNAs, which are fully 2′-O-methylated and have full phosphorothioate linkages, for their ability to suppress a level of a nuclear-localized long non-coding RNA, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1). The MALAT1 RNA is implied to be involved in stress responses and diseases including cancers. Specifically, we designed six 14-nt linear-type sgRNAs, sgRM1−sgRM6 that target the human MALAT1 RNA. sgRM1, sgRM2 and sgRM6 suppressed the MALAT1 RNA level, while the other sgRNAs showed little effect. In order to demonstrate that the suppression effect of sgRM1, sgRM2 and sgRM6 on the MALAT1 RNA level is caused by TRUE gene silencing, we performedin vitrotRNase ZLcleavage assay, microscopic analysis for nuclear existence of sgRNA, and tRNase ZLknockdown experiment. For thein vitrotRNase ZLcleavage assay, three 30-nt MALAT1 RNA fragments, TM1, TM2 and TM6 were prepared, which were RNA targets for sgRM1, sgRM2 and sgRM6, respectively. All of the sgRNAs guided recombinant tRNase ZLin vitroto cleave their own targets, although the cleavage efficiency changed depending on target/sgRNA pairs. By fluorescence microscopy, a 14-nt 5′-Alexa568-labeled sgRNA released from liposome was observed to be distributed ubiquitously in A549 cells with higher density in the nucleus, where both the target MALAT1 RNA and tRNase ZLexist. Knockdown of tRNase ZLby siRNA attenuated the suppression effect of sgRM1, sgRM2 and sgRM6 on the MALAT1 RNA level. We also demonstrated that the effective sgRNAs sgRM1, sgRM2 and sgRM6 reduce A549 cell viability.
Decoding Phenotypic Variability in Osteogenesis Imperfecta: Zebrafish as a Model for Molecular and Ultrastructural Insights
Authors: Debaenst Sophie , Sahd Lauren , Debaene Caitlin , Jarayseh Tamara , De Saffel Hanna , Bek Jan Willem , Steyaert Wouter , Van Haver Delphi , Dufour Sara , Impens Francis , Coucke Paul , De Clercq Adelbert , Willaert Andy
Published: January 2025

Phenotypic variability is common in human diseases, even when the same genes are affected. In this study, three zebrafish models of Osteogenesis Imperfecta (OI) with dominant glycine substitutions in type I collagen genes (col1a1amh13/+,col1a1adc124/+, andcol1a2mh15/+) were characterized for phenotypic severity and variability, using a newly developed standardized scoring system. Comprehensive analyses of the vertebral columns in these models revealed histological and ultrastructural differences that corresponded with phenotypic severity. Increasing skeletal severity correlated with a higher incidence of skeletal deformities and abnormalities. This, in turn, was associated with thinner bones and increased disorganization of collagen fibrils, fiber accumulation and mineralization, elastin deposits, and increased cell proliferation in the notochord and intervertebral ligament (IVL). Additionally, osteoblast function and bone regenerative capacity were increasingly compromised. These characteristics, combined with genetic information, have the potential to predict the severity of phenotypic outcomes in dominant forms of OI, caused by mutations in type I collagen. A remarkable intra-familial phenotypic variability in thecol1a2mh15/+mutant holds potential for future approaches that could help in understanding the underlying mechanisms of this variability and the identification of modifier genes. Finally, through proteomics analysis three potential protein biomarkers (HSP47, Col8a1, and Bcan) were identified, that could serve as indicators of disease severity. These biomarkers not only have diagnostic value, but will allow stratification by OI type, have predictive value towards progression of the clinical presentation and will play a role in treatment guidance. Validation in human tissue samples will further reveal their clinical relevance.

Significance Statement

Phenotypic variability in human diseases, such as Osteogenesis Imperfecta (OI), remains poorly understood. Using zebrafish models with dominant glycine substitutions in type I collagen, this study links genetic mutations to phenotypic severity through standardized scoring and detailed ultrastructural and molecular analyses. Key findings include skeletal abnormalities, compromised osteoblast function, and intra-familial phenotypic variability, suggesting the role of modifier genes. Proteomics identified three potential biomarkers (HSP47, Col8a1, and Bcan) with diagnostic and prognostic value. These results provide critical insights into genotype-phenotype correlations, offering a foundation for personalized approaches to diagnosis, stratification, and treatment of OI and related disorders.
Conformational and Functional Regulation of SET by Legumain Cleavage
Authors: Horak Carina , Wieland Alexander C. , Klaushofer Rupert , Briza Peter , Brandstetter Hans , Dall Elfriede
Published: January 2025

The cysteine protease legumain typically localizes to the endolysosomal system, where it is an important player in the immune system. However, in the context of Alzheimer’s disease (AD), legumain has been shown to be translocated to the cytosol, where it cleaves SET, synonymously termed TAF-1 or I2PP2A, an inhibitor of protein phosphatase 2A. SET is primarily found in the nucleus, where it regulates gene transcription, cell cycle progression, and histone acetylation, but can also translocate to the cytoplasm where it regulates cell migration and is implicated in neuronal apoptosis in AD. In this study, we demonstrate that legumain cleaves SET at two major sites: Asn16 at the N-terminal end and Asn175 at the earmuff domain. Contrary to previous findings, our biochemical and crystallographic experiments reveal that the corresponding N- and C-terminal cleavage products remain bound in a stable complex, rather than dissociating. Additionally, we show that the C-terminal acidic stretch of SET is essential for its binding to histone 1, and that cleavage impairs this interaction. Finally, we demonstrate that SET positively modulates PP2A activity. This effect is however abolished upon cleavage by legumain.
Molecular mechanisms of plastic biodegradation by the fungusClonostachys rosea
Authors: Gambarini Victor , Pavlov Nikolai , Young Paul , Dawes Stephanie , Auffret Arnaud , Kingsbury Joanne M. , Donaldson Lloyd A. , Smith Dawn A. , Weaver Louise , Pantos Olga , Handley Kim M. , Lear Gavin
Published: January 2025

Microbial degradation provides an avenue for the remediation of select plastic polymers contributing to the urgent environmental problem of global plastic pollution. We demonstrate the degradation of polycaprolactone (PCL) byClonostachys roseaand elucidate its underlying molecular mechanisms. We constructed the genome of this fungal strain and monitored changes in gene expression when exposed to PCL. Twelve genes linked to PCL degradation were found in the genome ofC. rosea, and some of them were upregulated in the presence of the plastic, including genes coding for two cutinases. We heterologously expressed the enzymes coded by both genes and confirmed their activity against PCL polymers. We also demonstrate that one of the enzymes was active against polyethylene terephthalate (PET) polymers. Glucose inhibited the expression of both genes, completely halting the plastic biodegradation process, possibly serving as a preferred and readily metabolisable carbon source compared with PCL. We confirm the presence of key metabolic pathways linked to PCL degradation inC. rosea, including fatty acid degradation, providing further evidence of the mechanisms central to plastic biodegradation.
Benchmarking And Datasets For Ambient Clinical Documentation: A Scoping Review Of Existing Frameworks And Metrics For AI-Assisted Medical Note Generation
Authors: Gebauer Sarah
Published: January 2025

Background

The increasing adoption of ambient artificial intelligence (AI) scribes in healthcare has created an urgent need for robust evaluation frameworks to assess their performance and clinical utility. While these tools show promise in reducing documentation burden, there remains no standardized approach for measuring their effectiveness and safety.

Objective

To systematically review existing evaluation frameworks and metrics used to assess AI-assisted medical note generation from doctor-patient conversations, and provide recommendations for future evaluation approaches.

Methods

A scoping review following PRISMA guidelines was conducted across PubMed, IEEE Explore, Scopus, Web of Science, and Embase to identify studies evaluating ambient scribe technology between 2020-2025. Studies were included if they were peer-reviewed, focused on clinical ambient scribe evaluation from speaking to note production, and described an evaluation approach. Extracted data included evaluation metrics, benchmarking approaches, dataset characteristics, and model performance.

Results

Seven studies met inclusion criteria. Evaluation approaches varied widely, from traditional natural language processing metrics like ROUGE and BERTScore to domain-specific measures such as clinical accuracy and bias. Critical gaps identified include: 1) wide diversity of evaluation metrics making cross-study comparison challenging, 2) limited integration of clinical relevance in automated metrics, 3) lack of standardized approaches for crucial metrics like hallucinations and errors, and 4) minimal diversity in clinical specialties evaluated. Only two datasets were publicly available for benchmarking.

Conclusions

This review reveals significant heterogeneity in how ambient scribes are evaluated, highlighting the need for standardized evaluation frameworks. We propose recommendations for developing comprehensive evaluation approaches that combine automated metrics with clinical quality measures. Future work should focus on creating public benchmarks across diverse clinical settings and establishing consensus on critical safety and quality metrics.
Federated Prediction Models and External Validation for Radiotherapy Outcomes in Oropharyngeal Cancer using F.A.I.R. Clinical and Radiomics Data
Authors: Gouthamchand Varsha , Gottardelli Benedetta , Kulkarni Gauri , Sherkhane Umesh B , Hogenboom Joshi , Subramanian Rajamenakshi , Jha Ashish Kumar , Mithun Sneha , Purandare Nilendu C , Agarwal Jai Prakash , Sekar Krithikaa , Lohith G. , Laskar Sarbani G , Sinha Shwetabh , Hoebers Frank JP , Rangarajan Venkatesh , Sunder Gaur , Dekker Andre , Soest Johan van , Wee Leonard
Published: January 2025

Development and validation of outcome prediction models in multi-centric cancer datasets are essential to ensure their applicability and accuracy across diverse populations. This study addresses the challenges of model generalizability in Head and Neck cancer research by utilizing combined clinical and radiomics data from centers in India and the Netherlands, following Findable-Accessible-Interoperable-Reusable (F.A.I.R.) data principles. We use Vantage6, a federated learning software infrastructure that implements the Personal Health Train (PHT) paradigm to ensure data privacy and security during collaborative research. Correlation-based Feature Selection (CFS) and LASSO regularized Cox regression were used to identify key features in training Cox proportional hazards models to predict Overall Survival (OS), Distant Metastasis (DM), and Locoregional Recurrence (LRR) in six datasets totaling 1131 oropharyngeal cancer patients. Our results highlight the efficacy of federated learning in providing a secure environment for multi-centric cancer research, enabling the development and validation of predictive models while upholding patient data confidentiality.
Reevaluating the Role of Education in Cognitive Decline and Brain Aging: Insights from Large-Scale Longitudinal Cohorts across 33 Countries
Authors: Fjell Anders M. , Røgeberg Ole , Sørensen Øystein , Amlien Inge K. , Bartrés-Faz David , Brandmaier Andreas M. , Cattaneo Gabriele , Düzel Sandra , Grydeland Håkon , Henson Richard N. , Kühn Simone , Lindenberger Ulman , Lyngstad Torkild Hovde , Mowinckel Athanasia M , Nyberg Lars , Pascual-Leone Alvaro , Solé-Padullés Cristina , Sneve Markus H. , Solana Javier , Strømstad Marie , Watne Leiv Otto ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Vietnam Era Twin Study of Aging, Walhovd Kristine B. , Vidal-Piñeiro Didac
Published: January 2025

Why education is linked to higher cognitive function in aging is fiercely debated. Leading theories propose that education reduces brain decline in aging, enhances tolerance to brain pathology, or that it does not affect cognitive decline but rather reflects higher early-life cognitive function. To test these theories, we analyzed 407.356 episodic memory scores from 170.795 participants >50 years, alongside 15.157 brain MRIs from 6.472 participants across 33 Western countries. More education was associated with better memory, larger intracranial volume and slightly larger volume of memory-sensitive brain regions. However, education did not protect against age-related decline or weakened effects of brain decline on cognition. The most parsimonious explanation for the results is that the associations reflect factors present early in life, including propensity of individuals with certain traits to pursue more education. While education has numerous benefits, the notion that it provides protection against cognitive or brain decline is not supported.
Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2
Authors: Jochim Briar E. , Topalidou Irini , Lehrbach Nicolas J
Published: January 2025

The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation of proteasome subunit genes and is essential for adaptation to proteotoxic stress. Nrf2/NFE2L2 is mainly involved in activating oxidative stress responses and promoting xenobiotic detoxification. Nrf1 and Nrf2 contain very similar DNA binding domains and can drive similar transcriptional responses. InC. elegans, a single gene,skn-1, encodes distinct protein isoforms, SKN-1A and SKN-1C, that function analogously to mammalian Nrf1 and Nrf2, respectively, and share an identical DNA binding domain. Thus, the extent to which SKN-1A/Nrf1 and SKN-1C/Nrf2 functions are distinct or overlapping has been unclear. Regulation of the proteasome by SKN-1A/Nrf1 requires post-translational conversion of N-glycosylated asparagine residues to aspartate by the PNG-1/NGLY1 peptide:N-glycanase, a process we term ‘sequence editing’. Here, we reveal the consequences of sequence editing for the transcriptomic output of activated SKN-1A. We confirm that activation of proteasome subunit genes is strictly dependent on sequence editing. In addition, we find that sequence edited SKN-1A can also activate genes linked to redox homeostasis and xenobiotic detoxification that are also regulated by SKN-1C, but the extent of these genes’ activation is antagonized by sequence editing. Using mutant alleles that selectively inactivate either SKN-1A or SKN-1C, we show that both isoforms promote optimal oxidative stress resistance, acting as effectors for distinct signaling pathways. These findings suggest that sequence editing governs SKN-1/Nrf functions by tuning the SKN-1A/Nrf1 regulated transcriptome.
Obligate cross-feeding of metabolites is common in soil microbial communities
Authors: Yousif Ghada , Zorrilla Francisco , Dash Swagatika , Oña Leonardo , Shekhar Aditi , Giri Samir , Guan Rui , Harshe Sharvari , Itermann Michael , Welter Daphne , Benes Vladimir , Patil Kiran R. , Kost Christian
Published: January 2025

Many microorganisms are refractory to laboratory cultivation. One possible explanation, known as the great plate count anomaly, is metabolic dependencies among community members. However, systematic studies of these interactions in communities like soil are missing, hindering advances in understanding these ecologically important ecosystems. Here, we address this issue by systematically analysing 6,931 bacterial isolates of 27 soil microbial communities. We find that the growth of up to 50% of all community members depended essentially on supplementation with amino acids, vitamins, or nucleotides. In 73% of cases, supplementation with multiple amino acids was necessary. Genomic analysis of 62 strains revealed that accumulation of insertion sequences and specific gene loss was associated with the observed auxotrophies. Finally, genome-scale metabolic models, computational analyses, and cocultivation experiments demonstrated that other co-occurring genotypes complemented the metabolic needs of auxotrophs, thus facilitating their growth. Our results demonstrate that soil bacteria exist within integrated metabolic networks, which hampers their cultivation.
DMB labelling for detection and analysis of capsular polysaccharides
Authors: Rutschmann Christoph , Vershynina Kateryna , Mathew Corina , Piëch Lucas , Sulewska Małgorzata , Schilling Philipp E , Wenner Nicolas , Larsson Louise , Bertola Anouk , Barazzone Elisa Cappio , Domocos Ioana , Mores Carine Roese , Ndem-Galbert Jackie Raisse , Turgay Yagmur , Schumann Raffael , de Viragh Shirin , Lavender Hayley , Tang Chris , Diard Médéric , Sunagawa Shinichi , Wetter Michael , Fiebig Timm , Slack Emma , Keys Timothy G
Published: January 2025

Bacterial capsules are major virulence factors enabling systemic infection by undermining innate and adaptive immunity. Capsular polysaccharides are also the antigen in some of the most successful antibacterial vaccines – including the pneumococcal, neisserial and Hib conjugate vaccines. However, it remains exceptionally challenging to study capsules, primarily due to their high chemical diversity and the limited methods available for their detection and analysis. We describe a robust biochemical method for detection and analysis of ABC transporter-dependent capsular polysaccharides, a major class of capsules that are associated with extraintestinal pathogenicEscherichia coli(ExPEC). The method involves release and fluorescent tagging of polysaccharides from the cell surface. Anion exchange chromatography of labelled samples reveals the presence, relative abundance, and length-distribution of these diverse polysaccharide antigens. The method provides a modern approach to detecting the capsule phenotype, bridging a critical gap left by the decline of serotyping assays. It will enhance our understanding of fundamental capsule biology and advance the development of capsule-targeting vaccines.
A cell type-specific mechanism driving the rapid antidepressant effects of transcranial magnetic stimulation
Authors: Gongwer Michael W. , Qi Alex , Enos Alexander S. , Rueda Mora Sophia A. , Klune Cassandra B. , Shari Meelan , Kashay Adrienne Q. , Williams Owen H. , Hacking Aliza , Riley Jack P. , Wilke Gary A. , Yang Yihong , Lu Hanbing , Leuchter Andrew F. , DeNardo Laura A. , Wilke Scott A.
Published: January 2025

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for brain disorders, but its therapeutic mechanism is unknown. We developed a novel mouse model of rTMS with superior clinical face validity and investigated the neural mechanism by which accelerated intermittent theta burst stimulation (aiTBS) – the first rapid-acting rTMS antidepressant protocol – reversed chronic stress-induced behavioral deficits. Using fiber photometry, we showed that aiTBS drives distinct patterns of neural activity in intratelencephalic (IT) and pyramidal tract (PT) projecting neurons in dorsomedial prefrontal cortex (dmPFC). However, only IT neurons exhibited persistently increased activity during both aiTBS and subsequent depression-related behaviors. Similarly, aiTBS reversed stress-related loss of dendritic spines on IT, but not PT neurons, further demonstrating cell type-specific effects of stimulation. Finally, chemogenetic inhibition of dmPFC IT neurons during rTMS blocked the antidepressant-like behavioral effects of aiTBS. Thus, we demonstrate a prefrontal mechanism linking rapid aiTBS-driven therapeutic effects to cell type-specific circuit plasticity.
Identification of Scaffold Specific Energy Transfer Networks in the Enthalpic Activation of Orotidine 5’-Monophosphate Decarboxylase
Authors: Dubey Pankaj , Somani Anish , Lin Jessica , Iavarone Anthony T. , Klinman Judith P.
Published: January 2025

Abstract

Orotidine 5’-monophosphate decarboxylase (OMPDC) is one of the most efficient enzyme systems studied, enhancing the decarboxylation of OMP to uridine 5’-monophosphate (UMP) by ca. 17 orders of magnitude, primarily by reducing the enthalpy of activation by ca. 28 kcal/mol. Despite a substantial reduction in activation enthalpy, OMPDC requires 15 kcal/mol of activation energy post- ES complex formation. This study investigates the physical basis of how thermal energy from solvent collisions is directed into the active site of enzyme to enable efficient thermal activation of the reaction. Comparative study of temperature-dependent hydrogen-deuterium exchange mass spectrometry (TDHDX) for WT and mutant forms of enzymes has recently been shown to uncover site specific protein networks for thermal energy transfer from solvent to enzyme active sites. In this study, we interrogate region-specific changes in the enthalpic barrier for local protein flexibility using a native OMPDC fromMethanothermobacter thermautotrophicus(Mt-OMPDC) and a single site variant (Leu123Ala) that alters the activation enthalpy for catalytic turnover. The data obtained implicate four spatially resolved, thermally sensitive networks that originate at different protein/solvent interfaces and terminate at sites surrounding the substrate near the substrate phosphate-binding region (R203), the substrate- ribose binding region (K42), and a reaction enhancing loop5 (S127). These are proposed to act synergistically, transiently optimizing the position and electrostatics of the reactive carboxylate of the substrate to facilitate activated complex formation. The uncovered complexity of thermal activation networks in Mt-OMPDC distinguishes this enzyme from other members of the TIM barrel family previously investigated by TDHDX. The new findings extend the essential role of protein scaffold dynamics in orchestrating enzyme activity, with broad implications for the design of highly efficient biocatalysts.
Dopamine signaling drives skin invasion by human-infective nematodes
Authors: Patel Ruhi , Romero Aracely Garcia , Bryant Astra S. , Agak George W. , Hallem Elissa A.
Published: January 2025

Skin-penetrating nematodes are one of the most prevalent causes of disease worldwide – nearly 15% of the global population is infected with at least one species of skin-penetrating nematode1,2. The World Health Organization has targeted these parasites for elimination by 20303, but the lack of preventative measures is a major obstacle to this goal. The infective larvae of skin-penetrating nematodes enter hosts through skin4, and blocking skin penetration is an as-yet unexplored approach for preventing infection. However, in order to prevent worm ingress via the skin, an understanding of the behavioral and neural mechanisms that drive skin penetration is required. Here, we describe the skin-penetration behaviors of the human-infective threadwormStrongyloides stercoralis. Using fluorescently labeled worms to enable visualization on the skin coupled with time-lapse microscopy, we show thatS. stercoralisengages in repeated cycles of pushing, puncturing, and crawling on the skin surface before penetrating the skin. Pharmacological inhibition of dopamine signaling inhibits these behaviors inS. stercoralisand the human hookwormAncylostoma ceylanicum,suggesting a critical role for dopamine signaling in driving skin penetration across distantly related nematodes. CRISPR-mediated disruption of dopamine biosynthesis and chemogenetic silencing of dopaminergic neurons also inhibit skin penetration. Finally, inactivation of the TRPN channel TRP-4, which is expressed in the dopaminergic neurons, blocks skin penetration on both rat and human skin. Our results suggest that drugs targeting TRP-4 and other nematode-specific components of the dopaminergic pathway could be developed into topical prophylactics that block skin penetration, thereby preventing infections.
Visual Influence Networks in Walking Crowds
Authors: Yoshida Kei , di Bernardo Mario , Warren William H.
Published: January 2025

Collective motion in human crowds has been understood as a self-organizing phenomenon that is generated from local visual interactions between neighboring pedestrians. To analyze these interactions, we introduce an approach that estimates local influences in observational data on moving human crowds and represents them as spatially-embedded dynamic networks (visual influence networks). We analyzed data from a human “swarm” experiment (N= 10, 16, 20) in which participants were instructed to walk about the tracking area while staying together as a group. We reconstructed the network every 0.5 seconds using Time-Dependent Delayed Correlation (TDDC). Using novel network measures of local and global leadership (direct influenceandbranching influence), we find that both measures strongly depend on an individual’s spatial position within the group, yielding similar but distinctive leadership gradients from the front to the back. There was also a strong linear relationship between individual influence and front-back position in the crowd. The results reveal that influence is concentrated in specific positions in a crowd, a fact that could be exploited by individuals seeking to lead collective crowd motion.
Ultrastructure analysis of mitochondria, lipid droplet and sarcoplasmic reticulum apposition in human heart failure
Authors: Latchman Nadina R. , Stevens Tyler L. , Bedi Kenneth C. , Prosser Benjamin L. , Margulies Kenneth B. , Elrod John W.
Published: January 2025

Background

Cardiomyocyte structural remodeling is reported as a causal contributor to heart failure (HF) development and progression. Growing evidence highlights the role of organelle apposition in cardiomyocyte function and homeostasis. Disruptions in organelle crosstalk, such as that between the sarcoplasmic reticulum (SR) and mitochondria, are thought to impact numerous cellular processes such as calcium handling and cellular bioenergetics; two processes that are disrupted and implicated in cardiac pathophysiology. While the physical distance between organelles is thought to be essential for homeostatic cardiomyocyte function, whether the interactions and coupling of organelles are altered in human heart failure remains unclear.

Methods

Here, we utilized transmission electron microscopy and careful quantification of ultrastructure to characterize the changes in organelle apposition in cardiomyocytes isolated from the hearts of patients diagnosed with various types of HF. Subsequently we employed molecular approaches to examine the expression of proposed organelle tethers.

Results

We demonstrate that cardiomyocytes isolated from dilated cardiomyopathy, hypertrophic cardiomyopathy and ischemic cardiomyopathy hearts display smaller, more rounded mitochondria, as compared to nonfailing controls. Failing cardiomyocytes also exhibited disrupted SR-mitochondria juxtaposition and changes in the expression of proposed molecular tethers. Further analysis revealed alterations in lipid droplet dynamics including decreased lipid droplet content and less lipid droplets in association with mitochondria in failing cardiomyocytes.

Conclusion

Here we observed changes in organelle dynamics in cardiomyocytes isolated from heart failure patients diagnosed with differing etiologies. Our results suggest that organelle structure and apposition may be a ubiquitous contributor to human HF progression.

RESEARCH PERSPECTIVE

What is New?

We provide a detailed analysis of organelle apposition in human heart failure, which has been understudied, and report that that failing human cardiomyocytes display an increase in distance between mitochondria and both the sarcoplasmic reticulum and lipid droplets.

Structural changes in organelles are correlated with the expression of proposed organelle tethers.

Resource of ultrastructural changes in organelle apposition in human heart failure resulting from various etiologies.

What Questions Should be Addressed next?

The results from this study provide rationale for causal experimentation to elucidate the contribution of organelle apposition to the progression of heart failure. Future studies examining mechanisms of mitochondrial tethering to the SR or lipid droplet will evaluate specific targets for therapeutic application.
Corticospinal Excitability in Response to Mediolateral Gait Instability
Authors: Bruijn Sjoerd , Davies Jennifer , Huiberts Raven Olof
Published: January 2025

Unpredictable gait disturbances, particularly in the mediolateral direction, pose a significant challenge to stability and are a common contributor to falls. Although the corticospinal tract is critical for gait and postural control, its response to such instabilities remains unclear. To investigate if corticospinal excitability increases during unpredictable lateral destabilisations, single-pulse transcranial magnetic stimulations were delivered over the primary motor cortex of 15 healthy individuals during steady-state and randomly laterally destabilised treadmill gait. Full-body kinematics were recorded using an optoelectronic motion capture system. Stimulations where the coil was >5 mm from the target location on the head were excluded. Corticospinal excitability was quantified for four upper- and three lower-leg muscles as the amplitude of the motor evoked potential (MEP) and compared between steady-state and destabilised gait. Lateral destabilisation resulted in a wider step width and shorter stride duration with increased variability and greater dynamic instability. Foot placement control during laterally destabilised gait was increased at midstance and there was also an increased average foot placement error in this condition. No differences in corticospinal excitability were observed in the lower-leg muscles. All upper-leg muscles demonstrated greater absolute MEPs in destabilised relative to steady-state gait. After normalising to muscle activity these periods became less pronounced, however, increases in corticospinal excitability during destabilised gait were observed in all but the gastrocnemius muscles. These finding suggest a heightened readiness of the corticospinal tract projecting to upper-leg muscles during destabilised gait, which could reflect general stabilising strategies such as decreasing stride time and increasing step width. Increases in the relative contribution of the corticospinal tract (i.e. normalised MEPs) were primarily noted during periods of low muscle activity, possibly hinting towards greater motor planning.
Conventional and
XYZ
charmonium states in a relativistic screened potential model
Authors: Bokade Chaitanya Anil , Bhaghyesh
Published: January 2025

In this work a comprehensive analysis of the mass spectrum and decay properties of charmonium states within a relativistic framework is carried out. The present experimental status of charmonium states is reviewed. Utilizing a screened potential model, we compute the spectra and various decay widths for the cc¯ bound system, comparing our results with experimental data and existing theoretical models. We calculate the decay constants, E1 and M1 transitions, and annihilation decay widths, confirming the consistency of our model with experimental observations for well-established charmonium states. The interpretation of charmoniumlike states X(4140), X(4274), and X(4500) as P-wave charmonium states and ψ(4040), ψ(3770), ψ(4160), ψ(4230), ψ(4360), ψ(4415), Y(4500), and Y(4360) as S−D mixed charmonium states is carried out.

Published by the American Physical Society
2025
Is the finite temperature effective potential effective for dynamics?
Authors: Herring Nathan , Cao Shuyang , Boyanovsky Daniel
Published: January 2025

We study the applicability of the finite temperature effective potential in the equation of motion of a homogeneous “misaligned” scalar condensate φ and find important caveats that severely restrict its domain of validity: (i) the of local thermodynamic equilibrium is in general not warranted, (ii) we show a direct relation between the effective potential and the thermodynamic entropy density S=−∂Veff(T,φ)/∂T, which entails that for a dynamical φ(t) the entropy becomes a nonmonotonic function of time, (iii) parametric instabilities in both cases with and without spontaneous symmetry breaking lead to profuse particle production with nonthermal distribution functions, (iv) in the case of spontaneous symmetry breaking spinodal instabilities yield a complex effective potential, internal energy and , an untenable situation in thermodynamics. All these caveats associated with using the effective potential in the of the condensate cannot be overcome by finite temperature equilibrium resummation schemes. We argue that the dynamics of the condensate leads to decoupling and freeze-out from local thermodynamic equilibrium, and propose a quantum system approach based on unitary time evolution. It yields the correct equations of motion without the caveats of the effective potential, and provides a fully renormalized and thermodynamically consistent framework to study the dynamics of the “misaligned” condensate, with real and conserved energy and entropy amenable to numerical study. The evolution of the condensate leads to profuse with nonthermal distribution functions. Possible emergent asymptotic nonthermal states and eventual rethermalization are conjectured.

Published by the American Physical Society
2025
Variability in Protein Expression and Fitness Under Stress: Distinct Modes of Early Adaptation of Populations
Authors: Knafo Maor , Rezenman Shahar , Nevo Reinat , Tsigalnitski Ivgeni , Reich Ziv , Kapon Ruti
Published: January 2025

Early proteomic adaptations in cells serve as an initial line of defense, allowing populations to cope with environmental changes before long-term genetic alterations occur. Therefore, they are important in determining the trajectory taken by populations experiencing stress. Using a representative set of genes and DNA barcoding in , we examine how two facets of these adaptations, gene expression and fitness, are distributed within populations experiencing different types and levels of abiotic stress. Together, our data reveal two fundamentally distinct modes of population-level stress response in yeast. The first mode is complex and exploratory, in which individual members adjust the expression of a large part of their genes, seemingly searching phenotypic space for a solution. This leads to phenotypic and fitness heterogeneity within the population. The second mode is degenerate, with all individuals adopting similar gene-expression levels and obtaining uniform fitness. The first mode is employed when a prevalent stress is encountered, and the second under a rare one. This hints at a role for historical encounters in phenotypic plasticity.

Published by the American Physical Society
2025
On the deprotonation of chlorothiazide
Authors: Brydson Rowan K. H. , Gray Morven L. , Kennedy Alan R. , O'Hara Benjamin C. , Reid Michael W. , Ugbolue Ifeka
Published: January 2025

Three alkali metal salt forms of the diuretic chlorothiazide (systematic name: 6-chloro-1,1-dioxo-2H-1,2,4-benzothiazine-7-sulfonamide, HCTZ) are described. When crystallized from aqueous solution, the Na and K salts, namely, poly[[μ-aqua-aqua(μ3-6-chloro-1,1-dioxo-7-sulfamoyl-2H-1,2,4-benzothiadiazin-2-ido)sodium] hemihydrate], {[Na(C7H5ClN3O4S2)(H2O)2]·0.5H2O}
n
, and poly[[diaqua(μ5-6-chloro-1,1-dioxo-7-sulfamoyl-2H-1,2,4-benzothiadiazin-2-ido)potassium] hemihydrate], {[K(C7H5ClN3O4S2)(H2O)2]·0.5H2O}
n
, are both found to have stoichiometry MCTZ·2.5H2O, with CTZ deprotonated at a heterocyclic ring N atom. Both the stoichiometry and the deprotonation site are different to those described in previously published versions of these structures. The Cs salt form is found to be the monohydrate CsCTZ·H2O, namely, poly[[aqua(μ5-6-chloro-1,1-dioxo-7-sulfamoyl-2H-1,2,4-benzothiadiazin-2-ido)caesium], [Cs(C7H5ClN3O4S2)(H2O)]
n
. As with the Na and K cognates, this structure is also deprotonated at the heterocyclic ring. NaCTZ is found to be a two-dimensional coordination polymer with bridges between Na centres formed by H2O and SO2 groups, and by links through the length of the coordinated CTZ anions. Water ligands in KCTZ and CsCTZ are terminal, rather than bridging between metal centres, but both compounds form structures where M—Cl interactions link two-dimensional motifs formed via M—O bonds (and in CsCTZ, M—N bonds) into three-dimensional coordination polymers.
Enhancing migrants’ job performance: the role of employees’ dynamic capabilities driven by the perceived meaning of life
Authors: Bieńkowska Agnieszka , Kubiciel-Lodzińska Sabina , Maj Jolanta , Tworek Katarzyna
Published: January 2025

Purpose

Amidst dynamic global changes, migrant workforce dynamics have become complex due to voluntary and forced migrations, coupled with talent competition. Paradoxically, many migrants experience deskilling and brain waste in host countries. To optimize migrant skills for enhanced job performance in fluctuating organizational and environmental contexts, it is vital to overcome this challenge. This study aims to verify the employees’ dynamic capabilities (EDC) based job performance model among migrants, exploring how the moderating effect of a meaning of life influences the relationship between EDC and job performance, considering job-related attitudes.

Design/methodology/approach

We conducted empirical research based on a survey of 453 Ukrainian migrants currently residing in Poland.

Findings

The results indicate that EDC influences job performance through person-job fit, work motivation, and job satisfaction. Particularly, migrants with a positive meaning of life show stronger relationships between EDC and job performance.

Originality/value

The article’s originality lies in exploring the concept of EDC within the context of migrant workers, bridging a gap in understanding how these capabilities impact job performance, particularly regarding brain waste and deskilling. The study delves into how EDC could mitigate the mismatch between migrant workers’ qualifications and job placements, thereby enriching international human resources management strategies to foster inclusive workplaces and enhance migrant workforce success.
Job seekers’ perceptions of corporate social responsibility practices (CSRP) and organisational attractiveness: a multi­group analysis
Authors: Ali Esrafil , R. Gupta Deepika
Published: January 2025

Purpose

This paper aims to model the impact of corporate social responsibility practices (CSRP) on job seekers’ organisational attractiveness (JSA) with particular reference to two Indian states, i.e. Andhra Pradesh (AP) and Odisha (OD). Further, the paper examines whether there are any significant variations in the perception of job seekers in these two states.

Design/methodology/approach

The sample for this exploratory research consisted of 943 business management students of AP and OD. The model was developed using the hierarchical component model method, and the associations were examined using partial least squares structural equation modeling (PLS-SEM). Furthermore, PLS-multi group analysis (PLS-MGA) was used to analyse the specific differences between two sample groups.

Findings

The study found that the CSR constructs, i.e. economical, legal, ethical and philanthropic, have a positive significant effect on CSRP for both groups of job seekers. The study also argued that the company selection by job seekers based on high or low CSR practices has no moderating effect on both sample groups for economical, legal, ethical and philanthropic dimensions. Further, the result revealed that the age and gender variables could not make any significant differences in the perceptions of job seekers.

Practical implications

The study provides research-based insights to relevant stakeholders (institutions, corporate, government and policymakers) that would be used in formulating strategies to strengthen the relationship between CSRP and JSA.

Originality/value

The study investigates CSR’s effect on organisational attractiveness from the theoretical lens of Carroll’s pyramid for two groups of job seekers. Limited studies have examined the complexity of this association with such a research context. The result guides educators, corporate, governments, practitioners and job seekers working on CSRP and JSA.
Achieving food supply chain sustainability through digital sharing platforms: prospects in China
Authors: Tian Shuang , Wu Lin , Pawar Kulwant S.
Published: January 2025

Purpose

Characterised by simultaneous food waste and shortages, our current food system is far from sustainable. Industry 4.0 has responded with technology-enabled innovations, including digital food-sharing platforms aimed at facilitating the efficient redistribution of surplus food. However, potential users often express reluctance to adopt such platforms, prompting this study to explore the underlying reasons for their hesitations.

Design/methodology/approach

This study was conducted in China, the world’s largest platform economy, where food-sharing platforms are notably absent. Using a vignette-based qualitative approach, semi-structured interviews were conducted with 35 potential users. The data were analysed through thematic analysis to uncover insights into adoption intentions.

Findings

The findings highlight the relevance of factors identified in existing technology acceptance theories, such as performance expectancy, effort expectancy, social influence, hedonic motivation, facilitating conditions and price value, in shaping adoption intentions. Additionally, content-specific and context-specific factors – such as trust in other users and the platform, concerns about “losing face” (mianzi) and safety concerns during the pandemic – emerged as critical influences on users' decisions to engage with these platforms.

Originality/value

This study contributes to scholarly discussions on enhancing the effectiveness of new technological innovations for food supply chain sustainability. The theoretical contributions expand the technology acceptance literature by incorporating factors related to platform service content and operating context.
Mapping the mindset for personal financial planning
Authors: Gupta Shelly , Mohammad Firoz
Published: January 2025

Purpose

The purpose of the study is to investigate the relationship between the big five personality traits and personal financial planning (PFP) by focusing on the mediating role of mental accounting among Indian service sector employees.

Design/methodology/approach

The present study used a data set comprising 649 valid responses obtained through the structured questionnaire that was specifically disseminated to employees working in the Indian service sector. Further, the study used a quantitative approach, partial least squares structural equation modeling, to examine the hypothesized relationship.

Findings

The study’s outcomes reveal that mental accounting completely mediates the relationship between conscientiousness and PFP. In addition, extraversion and neuroticism traits have directly influenced the PFP, but in the presence of mental accounting, these traits have partially influenced the PFP. Furthermore, the results suggest that agreeableness directly affects PFP, whereas openness does not demonstrate any significant influence.

Originality/value

The existing literature within the field of PFP has primarily focused on exploring various variables associated with mental accounting, such as monetary and time costs, mental budgeting process and tax liabilities. However, it has overlooked the potential mediating effect of mental accounting. This study bridges this gap by investigating the impact of mental accounting as a mediator in the relationship between personality traits and PFP. Moreover, recently, the Indian economy has undergone major overhauls especially due to enactment of Goods and Services Tax and the profound impact of COVID-19, leading to changes in financial behavior of individuals. Therefore, this study endeavors to shed light on the emerging dynamics within the PFP domain, particularly within the context of the newly accustomed economic circumstances in India.
Airline revenue management, distribution and passengers: market trends in a technology driven triangle
Authors: Poulaki Ioulia , Koufodontis Nikolaos Iason , Papadimitriou Sofia
Published: January 2025

Purpose

The aim of this paper is a first attempt to map and describe airline information systems (IS) market, in the context of the latest trends affecting air services distribution, revenue management (RM) and passengers in the airline industry.

Design/methodology/approach

RM evolution has greatly affected airline revenues and load factors in a global environment characterized by fierce competition. The distribution of air services has shifted gradually from a model dependent on travel agents and other intermediaries toward a new trend of do-it-yourself (DIY) bookings through the Internet. The resulting new and significantly more complex environment mandates the connection between revenue management systems (RMS) and reservation systems (RS) through third parties (aggregators) that have emerged and are ready to perform this task. In this context, a market review has been carried out, following the approach of a structured literature review to illustrate this ecosystem.

Findings

Data collected from the vendors depict the market size and capabilities, highlighting that the market for IS in the airline industry is based on a relational triangle of dependence and competition that includes RS, RMS and aggregators.

Originality/value

Mapping both technological and functional backgrounds and the operation of current distribution systems and their linking with RMS and methods is deemed a necessity for identifying and describing the mechanisms that are defining the B2B relationship and the subsequent need to improve the ways current distribution schemes combined with RM applications are addressing changing market needs, reflecting the new behavioral models of the customers.