bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody Library Design by Seeding Linear Programming with Inverse Folding and Protein Language Models
Authors: Hayes Conor F. , Magana-Zook Steven A. , Gonçalves Andre , Solak Ahmet Can , Faissol Daniel , Landajuela Mikel 
Published: November 2024

AbstractWe propose a novel approach for antibody library design that combines deep learning and multi-objective linear programming with diversity constraints. Our method leverages recent advances in sequence and structure-based deep learning for protein engineering to predict the effects of mutations on antibody properties. These predictions are then used to seed a cascade of constrained integer linear programming problems, the solutions of which yield a diverse and high-performing antibody library. Operating in acold-startsetting, our approach creates designs without iterative feedback from wet laboratory experiments or computational simulations. We demonstrate the effectiveness of our method by designing antibody libraries for Trastuzumab in complex with the HER2 receptor, showing that it outperforms existing techniques in overall quality and diversity of the generated libraries. Our source code is available athttps://github.com/LLNL/protlib-designer.
A novel open-source cultivation system helps establish the first full cycle chemosynthetic symbiosis model system involving the giant ciliateZoothamnium niveum
Authors: Contarini PE , Emboule E , Jean-Louis P , Woyke T , Date SV , Gros O , Volland J-M 
Published: November 2024

AbstractSymbiotic interactions drive species evolution, with nutritional symbioses playing vital roles across ecosystems. Chemosynthetic symbioses are globally distributed and ecologically significant, yet the lack of model systems has hindered research progress. The giant ciliateZoothamnium niveumand its sulfur-oxidizing symbionts represent the only known chemosynthetic symbiosis with a short life span that has been transiently cultivated in the laboratory. While it is experimentally tractable and presents a promising model system, it currently lacks an open-source, simple, and standardized cultivation setup. Following the FABricated Ecosystems (EcoFABs) model, we leveraged 3D printing and polydimethylsiloxane (PDMS) casting to develop simple flow-through cultivation chambers that can be produced and adopted by any laboratory. The streamlined manufacturing process reduces production time by 86% and cuts cost by tenfold compared to the previous system. Benchmarking using previously established optimal growth conditions, the new open-source cultivation system proves stable, efficient, more autonomous, and promotes a more prolific growth of the symbiosis. For the first time, starting from single cells, we successfully cultivated the symbiosis in flow-through chambers for 20 days, spanning multiple generations of colonies that remained symbiotic. They were transferred from chamber to chamber enabling long-term cultivation and eliminating the need for continuous field sampling. The chambers, optimized for live imaging, allowed detailed observation of the synchronized growth between the host and symbiont. Highlighting the benefit of this new system, we here describe a new step in the first hours of development where the host pauses growth, expels a coat, before resuming growth, hinting at a putative symbiont selection mechanism early in the colony life cycle. With this simple, open-source, cultivation setup,Z. niveumholds promises for comparative studies, standardization of research and wide adoption by the symbiosis research community.
Evaluating Combined Neurotoxicity of Amyloid Beta and Tau Oligomers in Alzheimer’s Disease: A New Criterion
Authors: Kuznetsov Andrey V. 
Published: November 2024

AbstractA criterion characterizing the combined neurotoxicity of amyloid beta and tau oligomers is suggested. A mathematical model that makes it possible to calculate a value of this criterion during senile plaque and NFT formation is proposed. Computations show that for physiologically relevant parameter values, the value of the criterion increases approximately linearly as time increases. Once the formation of neurofibrillary tangles starts in addition to the senile plaque formation, the slope characterizing the rate at which the criterion increases becomes larger. The critical value of the criterion upon reaching which the neuron dies is estimated. Computations predict that unless the production rates of amyloid beta and tau monomers are very large, in order for the accumulated toxicity to reach the critical value, the degradation machinery responsible for the degradation of amyloid beta and tau must become dysfunctional. The value of the criterion after 20 years of the aggregation process is strongly influenced by deposition rates of amyloid beta and tau oligomers into senile plaques and NFTs. This suggests that deposition of amyloid beta and tau oligomers into senile plaques and NFTs may reduce accumulated toxicity by sequestering more toxic oligomeric species into less toxic insoluble aggregates.
Stacked Human Arterial Endothelial Cells Generate Atherosclerotic Fatty Streaks and Release Proinflammatory Cytokines
Authors: Zeng Ye , Ouyang Zhi , Qiu Yan , Jiang Wenli , Jin Chen , Zhong Jian , Jin Linlu , Qin Yixue , Zhao Yunran , Zhou Xintong , Liu Xiaoheng , Fu Bingmei M. 
Published: November 2024

AbstractFatty streaks are the first sign of atherosclerosis. They consist of lipid-containing foam cells, which were believed to be derived from the monocytes in the blood through the leaky endothelium, and from the vascular smooth muscle cells migrating into the intima from the media. Here, we showed that fatty streaks can also be formed by the stacked human arterial endothelial cells (HAECs) cultured in vitro. Via SEM we revealed a novel cell phenotype (coralthelial) that forms a streak/coral-like structure. We observed accumulation of lipids in the coralthelial cell and increased Golgi and coat protein II markers in its nucleus. Additionally, proinflammatory cytokines were upregulated in these cells, likely due to Golgi nuclear translocation and subsequently increased expression of the ribosomal protein RPL23 in the nucleus. We demonstrated, for the first time, that the atherosclerotic fatty streak-like structure can be generated from the stacked HAECs, which also create a proinflammatory microenvironment.Significance StatementOur work presents a novel perspective on atherosclerotic fatty streak formation, a critical early event in atherosclerosis development. We demonstrate, for the first time, that human arterial endothelial cells (HAECs) can transform into a novel phenotype, termed “coralthelial cells”. These cells contribute to fatty streak formation, and produce proinflammatory cytokines through the relocation of RPL23 with the Golgi apparatus to the nucleus. This finding provides a new cellular mechanism by which endothelial cells initiate atherosclerosis, independent of traditional monocyte-derived foam cells. By enriching established paradigms, our research not only opens new avenues for therapeutic intervention targeting endothelial cells but also enhances understanding of vascular diseases and provides potential diagnostic and prognostic markers for atherosclerosis.
Peptide modified, programmable DNA tetrahedra to modulate autophagy in biological systems
Authors: Hema Naveena A , Kansara Krupa , Singh Nihal , Gupta Sharad , Kumar Ashutosh , Bhatia Dhiraj 
Published: November 2024

AbstractAutophagy is a critical cellular pathway for degrading and recycling damaged components, essential for maintaining cellular homeostasis. Dysregulation of autophagy contributes to various diseases, including neurodegenerative disorders, cancers, and metabolic syndromes, highlighting the therapeutic potential of controlled autophagy induction. However, current autophagy inducers often lack specificity and may inadvertently trigger apoptosis, limiting their clinical utility. Here, we present a DNA tetrahedron-BH3 peptide nanosystem (Tdpep) engineered to selectively induce autophagy by disrupting the Beclin 1-Bcl2 interaction, a pivotal regulatory point in autophagy initiation. Tdpep, functionalized with a BH3 peptide targeting Bcl2, demonstrated efficient cellular uptake and minimal cytotoxicity in HeLa cells at concentrations up to 200nM. Autophagy induction was confirmed by increased LC3B puncta formation and fluorescence intensity comparable to that induced by rapamycin. Autophagy flux analysis of Tdpep with bafilomycin A1 validated enhanced autophagic activity rather than flux inhibition. Furthermore, Tdpep treatment significantly reduced cellular ROS levels, indicating effective autophagic turnover. Apoptosis assays showed that Tdpep did not induce apoptosis, confirming its selective autophagy induction. Furthermore, Tdpep nanosystem also induced autophagy inDanio reriolarvae in vivo model. Thus, this targeted DNA tetrahedron nanosystem provides a precise autophagy modulation platform with minimized off-target effects, offering a promising therapeutic strategy for diseases associated with autophagy dysfunction.Graphical abstract
Endocytosis restricts synapse growth by attenuating Highwire/PHR1-dependent JNK signaling in a pathway parallel to the BMP signaling
Authors: Pippadpally Srikanth , Choudhury Saumitra Dey , Bisht Anjali , Dwivedi Manish Kumar , Mushtaq Zeeshan , Reddy-Alla Suneel , Kumar Vimlesh 
Published: November 2024

AbstractEndocytosis regulates the retrieval of synaptic membranes and the trafficking of growth signaling receptors. WhileDrosophilaendocytic mutants show synaptic overgrowth at the neuromuscular junctions (NMJs), the signaling pathways by which endocytosis restricts synapse growth remain poorly understood. Here, we demonstrate that σ2-adaptin, one of the obligate subunits of the AP2 complex, facilitates the degradation and trafficking of E3-ubiquitin ligase Highwire (Hiw)/PHR1 and inhibits the c-Jun N-terminal kinase (JNK) signaling. This function of σ2-adaptin is independent of its Bone Morphogenetic Protein (BMP) signaling regulation. Loss of σ2-adaptin leads to Hiw accumulation and mislocalization in the neuronal cell body, leading to elevated MAP3K Wallenda levels. Stabilizing Hiw by expressing Rae1 or genetically blocking the JNK signaling suppresses the synaptic overgrowth defects observed inσ2-adaptinmutants. Remarkably, blocking BMP and JNK signaling pathways suppressed the synaptic overgrowth observed in theσ2-adaptinmutant to the wild-type levels. Finally, we show that loss of Rab11 but not Rab5 or Rab7 leads to accumulation/mislocalization of Hiw in the neuronal cell body akin toσ2-adaptinmutants. We propose a model in which endocytosis regulates Rab11-mediated Hiw trafficking and attenuates JNK signaling in a pathway parallel to the BMP signaling to restrict synaptic growth.
Energy depletion and re-acceleration of driver electrons in a plasma-wakefield accelerator
Authors: Peña F. , Lindstrøm C. A. , Beinortaitė J. , Björklund Svensson J. , Boulton L. , Diederichs S. , Foster B. , Garland J. M. , González Caminal P. , Loisch G. , Schröder S. , Thévenet M. , Wesch S. , Wood J. C. , Osterhoff J. , D'Arcy R. 
Published: November 2024

For plasma-wakefield accelerators to fulfill their potential for cost effectiveness, it is essential that their energy-transfer efficiency be maximized. A key aspect of this efficiency is the near-complete transfer of energy, or depletion, from the driver electrons to the plasma wake. Achieving full depletion is limited by the process of re-acceleration, which occurs when the driver electrons decelerate to nonrelativistic energies, slipping backward into the accelerating phase of the wakefield and being subsequently re-accelerated. Such re-acceleration is unambiguously observed here for the first time. At this re-acceleration limit, we measure a beam driver depositing (57 ± 3)% of its energy into a 195-mm-long plasma. This suggests that the energy-transfer efficiency of plasma accelerators could approach that of conventional accelerators.

Published by the American Physical Society
2024
Implementation and evaluation of a mobile application to support occupational therapy education
Authors: Ruiz Fernández María Luisa , Márquez-Álvarez Luis-Javier , Jiménez-Arberas Estíbaliz , Fernández Méndez Isabel 
Published: November 2024

Purpose
This study aims to evaluate the usability and effectiveness of a mobile application, ValTO, designed to enhance communication and professional reasoning skills in occupational therapy students through a case-based learning approach.

Design/methodology/approach
A descriptive exploratory study was conducted with 32 second-year occupational therapy students. The usability of the app was assessed using the Mobile Application Rating Scale and the System Usability Scale, complemented by the University of Oviedo’s Learning Satisfaction Survey.

Findings
The majority of students (77.8%) rated the app above average on the System Usability Scale, with 50% scoring it as excellent. Mobile Application Rating Scale scores revealed high ratings across functionality, aesthetics and information quality, with a significant correlation between app usability and user satisfaction. Increased student satisfaction was also observed in the Learning Satisfaction Survey compared to previous years.

Originality/value
ValTO integrates modern mobile health tools into occupational therapy education, enhancing students’ decision-making skills in an innovative, real-world context. This study contributes to the growing body of research on mobile health applications in educational settings, demonstrating their potential to improve both student engagement and learning outcomes.
Is Cost of Equity Capital influenced by intellectual capital? An empirical analysis from the perspective of Indian companies
Authors: Ghosh Chiranjit 
Published: November 2024

PurposeThis empirical study is developed with an aim of exploring how and to what extent the current year’s as well as lagged years’ disclosure level of intellectual capital (IC) influences the firm's value which is measured through the Cost of Equity Capital.Design/methodology/approachThe content analysis technique is applied on the annual reports of 50 sample companies to construct an IC disclosure index for measuring the volume of IC disclosure and to collect other relevant information for the study periods from 2015–16 to 2019–20. However, due to unavailability of information for all the study periods, 7 companies were eliminated and finally 43 companies are used for analytical purpose. Keeping in mind about the aim of this research, regression equations are run to analyze the cause–effect relationship between the IC disclosure level and the Cost of Equity Capital after excluding the influence of other factors like firm size, unlevered beta and market-to-book ratio.FindingsThe present study finds that the amount of IC disclosure has an inverse association with the cost of equity capital. Our study also confirms that lagged years’ IC disclosure has a greater inverse effect than the current year’s IC disclosure on the Cost of Equity Capital.Originality/valueFor the first time in the literature of IC disclosure in the perspective of Indian context, this empirical study takes an initiative to investigate the impact of current year’s as well as backlog years’ IC disclosure level on the Cost of Equity Capital.
How long does purchase intention exist? “Buying intention survival”: a new insight into forecasting purchase intention abandonment
Authors: Baati Ons , Akrout Fathi 
Published: November 2024

Purpose
The purpose of this study is to predict the probability and duration of “Buying Intention Survival” (BIS) and to propose a conceptual framework illustrating its determinants. More specifically, it aims to determine the likelihood of buying intention abandonment (BIA) and the time frame in which the intention abandonment might occur.

Design/methodology/approach
The data for this study were collected using an online survey of a sample of 573 Tunisian consumers. The data were then subjected to a survival analysis. This method is used for the first time in this context.

Findings
Results show that the average duration of the BIS could extend over 162 months. Findings also suggest that involvement, anticipated regret linked to a no-purchase decision and social influence have a positive effect on BIS, whereas anticipated regret linked to purchase influences BIS negatively.

Practical implications
Accurately anticipating the date of BIA is of paramount importance for marketers as it allows them to implement strategies that reduce the risk of abandonment and encourage customers to promptly fulfill their purchasing intentions.

Originality/value
This paper introduces a new concept, namely, BIS, and applies a survival analysis method to determine whether purchase intention disappears over time, how soon it may disappear, and possible reasons this may occur.
Collaboration and perceived job demands, job control and social support in primary care: a social network approach
Authors: Väisänen Visa , Luke-Currier Addiena , Hietapakka Laura , Elovainio Marko , Sinervo Timo 
Published: November 2024

PurposeThis study aims to examine the associations of collaboration measured as social network characteristics with perceived job demands, job control and social support in primary healthcare professionals.Design/methodology/approachA cross-sectional study design incorporating social network analysis was utilized. Wellbeing surveys with a network questionnaire were sent to care personnel (physicians, nurses and allied health workers) of Finnish primary healthcare in December 2022 (n = 96). Correlation coefficients and multivariate linear regression modeling were used to analyze the associations.FindingsHigher level of collaboration (measured as number of connections in the network) was associated with lower perceived job demands and higher job control. Care professionals’ frequency of collaboration and proportion of connections with the same occupation (homophily) were borderline associated with social support, indicating further research needs. Larger professional networks, perhaps enabling better teamwork and sharing of workload or information, may directly or indirectly protect from job strain.Practical implicationsWork-related collaboration in primary care should be encouraged and large support networks need to be promoted further. Individuals, especially allied health workers, working in multiple locations or as a sole member of their occupation group in the work community need to be provided with adequate social support.Originality/valueSocial network analysis has been proposed as a tool to investigate care integration and collaboration, but direct analyses of network measures and validated wellbeing instruments have remained absent. This study illuminated the role of collaboration structures in work-related wellbeing of care professionals by showcasing the potential of social network analysis.
A case of indeterminate cell histiocytosis with ETV3‐NCOA2 translocation
Authors: Suzuki Norihito , Shimauchi Takatoshi , Baba Satoshi , Nagakura Yuka , Takahashi Juri , Ajima Sayaka , Tajima Mizuho , Kitauchi Yurie , Kageyama Reiko , Honda Tetsuya 
Published: November 2024

AbstractIndeterminate cell histiocytosis (ICH) is a rare histiocytic disorder characterized by a proliferation of CD1a+ and CD207/langerin− cells. Recent molecular analyses have identified ETV3‐NCOA2 translocation as a possible aetiopathogenesis of ICH. Herein, we describe the first Japanese case of ICH with ETV3‐NCOA2 translocation. A 79‐year‐old Japanese man presented with a 1‐year history of pruritic erythematous papules and nodules on his trunk and extremities. Histological examination revealed a dense and diffuse sheets–like infiltration of medium‐sized histiocyte‐like cells from the epidermis to the deep dermis. Immunohistochemically, the atypical cells were positive for CD1a but negative for CD207/langerin. Fluorescence in situ hybridization using NCOA2 break‐apart probes confirmed a chromosomal break occurring on NCOA2 monoallele in the tumor cells. Furthermore, ETV3 exon 4‐NCOA2 exon 14 translocation was identified in formalin‐fixed paraffin‐embedded skin samples using reverse transcription polymerase chain reaction and subsequent direct DNA sequencing. He also presented with interspersed eczematous plaques on his trunk and reactive dermatopathic lymphoadenopathy without any infiltration of ICH. He was treated with topical corticosteroids and narrowband UVB phototherapy. Four months later, his ICH skin eruptions, eczematous plaques, and lymphoadenopathy gradually regressed. Our case supports the notion that the detection of ETV3‐NCOA2 translocation can be useful for diagnosis of ICH.
Mycorrhizal specialization toward each distinct Oliveonia fungus in two closely related photosynthetic Dactylostalix orchids
Authors: Suetsugu Kenji , Okada Hidehito 
Published: November 2024

Abstract

Although rhizoctonias from Ceratobasidiaceae, Tulasnellaceae and Serendipitaceae are typical orchid mycobionts, orchid mycorrhizal fungi exhibit vast taxonomic and ecological diversity. This diversity stems from the high specificity of orchid mycorrhizal associations and the remarkable diversity of over 28,000 orchid species. The subtribe Calypsoinae is particularly notable for its diverse mycorrhizal partnerships, including rhizoctonias, ectomycorrhizal and saprotrophic non‐rhizoctonia fungi. However, the mycobionts within certain Calypsoinae lineages, such as the genus Dactylostalix, remain understudied. This study explores the physiological ecology of two photosynthetic Calypsoinae species, Dactylostalix ringens and Dactylostalix uniflora, to gain insight into potentially novel associations and their ecological implications.

We analysed the mycorrhizal communities of both Dactylostalix species using high‐throughput ITS metabarcoding of root samples collected from multiple locations. Additionally, we measured the natural abundances of 13C and 15N isotopes in the leaves of the two Dactylostalix species and their co‐occurring autotrophic reference plants, as well as in fungal pelotons isolated from D. ringens, to assess the potential for partial mycoheterotrophy.

Our findings revealed that D. ringens and D. uniflora form specialized mycorrhizal associations predominantly with distinct lineages of Oliveonia (Oliveoniaceae, Auriculariales), even in sympatric populations. Stable isotope analysis showed that both Dactylostalix species exhibited conflicting isotopic signals: elevated δ15N values, supporting partial mycoheterotrophy, but lower δ13C values compared to autotrophic plants, suggesting autotrophy. Peloton samples from D. ringens displayed only modest 13C enrichment relative to autotrophic references.

These conflicting isotopic signals make it difficult to precisely determine whether both Dactylostalix species are autotrophic or partially mycoheterotrophic. Intriguingly, the 13C and 15N signatures of Dactylostalix species and their pelotons resemble those of many rhizoctonia‐associated orchids. This isotopic evidence implies a niche overlap with endophytic tendencies between rhizoctonias and Oliveonia, suggesting that potential endophytic traits may have facilitated the recruitment of Oliveonia as novel mycorrhizal partners. Furthermore, the mycorrhizal segregation between D. ringens and D. uniflora likely promotes their sympatric coexistence and may contribute to reproductive isolation through ecological specialization.

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