bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing AF2’s ability to predict structural ensembles of proteins
Authors: Riccabona Jakob R. , Spoendlin Fabian C. , Fischer Anna-Lena M. , Loeffler Johannes R. , Quoika Patrick K. , Jenkins Timothy P. , Ferguson James A. , Smorodina Eva , Laustsen Andreas H. , Greiff Victor , Forli Stefano , Ward Andrew B. , Deane Charlotte M. , Fernández-Quintero Monica L. 
Published: April 2024

AbstractRecent breakthroughs in protein structure prediction have enhanced the precision and speed at which protein configurations can be determined, setting new benchmarks for accuracy and efficiency in the field. However, the fundamental mechanisms of biological processes at a molecular level are often connected to conformational changes of proteins. Molecular dynamics (MD) simulations serve as a crucial tool for capturing the conformational space of proteins, providing valuable insights into their structural fluctuations. However, the scope of MD simulations is often limited by the accessible timescales and the computational resources available, posing challenges to comprehensively exploring protein behaviors. Recently emerging approaches have focused on expanding the capability of AlphaFold2 (AF2) to predict conformational substates of protein structures by manipulating the input multiple sequence alignment (MSA). These approaches operate under the assumption that the MSA also contains information about the heterogeneity of protein structures. Here, we benchmark the performance of various workflows that have adapted AF2 for ensemble prediction focusing on the subsampling of the MSA as implemented in ColabFold and compare the obtained structures with ensembles obtained from MD simulations and NMR. As test cases, we chose four proteins namely the bovine pancreatic inhibitor protein (BPTI), thrombin and two antigen binding fragments (antibody Fv and nanobody), for which reliable experimentally validated structural information (X-ray and/or NMR) was available. Thus, we provide an overview of the levels of performance and accessible timescales that can currently be achieved with machine learning (ML) based ensemble generation. In three out of the four test cases, we find structural variations fall within the predicted ensembles. Nevertheless, significant minima of the free energy surfaces remain undetected. This study highlights the possibilities and pitfalls when generating ensembles with AF2 and thus may guide the development of future tools while informing upon the results of currently available applications.
Prediction of Cardiovascular Markers and Diseases Using Retinal Fundus Images and Deep Learning: A Systematic Scoping Review
Authors: Li Livie Yumeng , Isaksen Anders Aasted , Lebiecka-Johansen Benjamin , Funck Kristian , Thambawita Vajira , Byberg Stine , Andersen Tue Helms , Norgaard Ole , Hulman Adam 
Published: April 2024

AbstractBackgroundCardiovascular risk prediction models based on sociodemographic factors and traditional clinical measurements have received significant attention. With rapid development in deep learning for image analysis in the last decade and the well-known association between micro- and macrovascular complications, some recent studies focused on the prediction of cardiovascular risk using retinal fundus images. The objective of this scoping review is to identify and describe studies using retinal fundus images and deep learning to predict cardiovascular risk markers and diseases.MethodsWe searched MEDLINE and Embase for peer-reviewed articles on 17 November 2023. Abstracts and relevant full-text articles were independently screened by two reviewers. We included studies that used deep learning for the analysis of retinal fundus images to predict cardiovascular risk markers (e.g. blood pressure, coronary artery calcification, intima-media thickness) or cardiovascular diseases (prevalent or incident). Studies that used only predefined characteristics of retinal fundus images (e.g. tortuosity, fractal dimension) were not considered. Study characteristics were extracted by the first author and verified by the senior author. Results are presented using descriptive statistics.ResultsWe included 24 articles in the review, published between 2018 and 2023. Among these, 21 (88%) were cross-sectional studies and eight (33%) were follow-up studies with outcome of clinical CVD. Five studies included a combination of both designs. Most studies (n=23, 96%) used convolutional neural networks to process images. We found nine (38%) studies that incorporated clinical risk factors in the prediction and four (17%) that compared the results to commonly used clinical risk scores in a prospective setting. Three of these reported improved discriminative performance. External validation of models was rare (n=5, 21%). Only four (17%) studies made their code publicly available.ConclusionsThere is an increasing interest in using retinal fundus images in cardiovascular risk assessment. However, there is a need for more prospective studies, comparisons of results to clinical risk scores and models augmented with traditional risk factors. Moreover, more extensive code sharing is necessary to make findings reproducible and more impactful beyond a specific study.
Microbial resistance and resilience to drought under organic and conventional farming
Authors: Kost Elena , Kundel Dominika , Conz Rafaela Feola , Mäder Paul , Krause Hans-Martin , Six Johan , Mayer Jochen , Hartmann Martin 
Published: April 2024

AbstractThe impacts of climate change, such as drought, can affect soil microbial communities. These communities are crucial for soil functioning and crop production. Organic and conventional cropping systems promote distinct soil microbiomes and soil organic carbon contents, which might maintain different capacities to mitigate drought effects on cropping systems. A field-scale drought simulation was performed in long-term organically and conventionally managed cropping systems differing in fertilization and pesticide application. The soil microbiome was assessed during and after drought in bulk soil, rhizosphere, and roots of wheat. We found that drought shifted microbial community structures, affecting fungi more strongly than prokaryotes. Microbial communities associated with crops (i.e. rhizosphere and root) were more strongly influenced by drought compared to bulk soil communities. A drought legacy effect was observed in the bulk soil after harvesting and rewetting. The resistance and resilience of the soil microbiome to severe drought did not significantly differ across the organic and conventional cropping systems, although few individual genera (e.g.Streptomyces,Rhizophagus, Actinomadura, andAneurinibacillus) showed system-specific drought responses. All cropping systems showed relative increases in potential plant growth-promoting genera under drought. This agricultural field study indicated that fungal communities might be less resistant to drought than prokaryotic communities in cropping systems and these effects get more pronounced in closer association with plants. Organic fertilization or the reduction in pesticide application might not have the ability to buffer severe drought stress and additional farming practices might have to be incorporated to improve drought tolerance in cropping systems.
Protein design of two-component tubular assemblies like cytoskeletons
Authors: Noji Masahiro , Sugita Yukihiko , Yamazaki Yosuke , Miyazaki Makito , Suzuki Yuta 
Published: April 2024

AbstractRecent advances in protein design have ushered in an era of constructing intricate higher-order structures1. Despite this progress, orchestrating the assembly of diverse protein units into cohesive artificial structures akin to biological assembly systems, especially in tubular forms, remains an elusive goal. To address this, we introduce the Nature-Inspired Protein Assembly Design (NIPAD), a novel methodology that utilises two distinct protein units to create unique tubular structures under carefully designed conditions. These structures demonstrate dynamic flexibility similar to that of actin filaments, with cryo-electron microscopy revealing diverse morphologies, like microtubules. By mimicking actin filaments, helical conformations were incorporated into tubular assemblies, thereby enriching their structural diversity. Remarkably, these assemblies can be reversibly disassembled and reassembled in response to environmental stimuli, such as changes in salt concentration and temperature, mirroring the dynamic behaviour of natural systems. NIPAD combines rational protein design with biophysical insights, leading to the creation of biomimetic, adaptable, and reversible higher-order assemblies. This approach deepens our understanding of protein assembly design and complex biological structures. Concurrently, it broadens the horizons of synthetic biology and material science, holding significant implications for unravelling life’s fundamental processes and pioneering new applications.
IncC plasmid genome rearrangements influence the vertical and horizontal transmission tradeoff inEscherichia coli
Authors: Allain Margaux , Morel-Journel Thibaut , Condamine Bénédicte , Gibeaux Benoist , Gachet Benoit , Gschwind Rémi , Denamur Erick , Landraud Luce 
Published: April 2024

ABSTRACTIt has been shown that an evolutionary tradeoff between vertical (host growth rate) and horizontal (plasmid conjugation) transmissions contribute to global plasmid fitness. As conjugative IncC plasmids are important for the spread of multidrug resistance (MDR), in a broad range of bacterial hosts, we investigated vertical and horizontal transmissions of two multidrug-resistant IncC plasmids according to their backbones and MDR-region rearrangements, upon plasmid entry into a new host. We observed plasmid genome deletions after conjugation in three diverse naturalEscherichia coliclinical strains, varying from null to high number depending on the plasmid, all occurring in the MDR-region. The plasmid burden on bacterial fitness depended more on the strain background than on the structure of the MDR-region, deletions appearing to have no impact. Besides, we observed an increase in plasmid transfer rate, from ancestral host to new clinical recipient strains, when the IncC plasmid was rearranged. Finally, using a second set of conjugation experiments, we investigated the evolutionary tradeoff of the IncC plasmid during the critical period of plasmid establishment inE. coliK-12, by correlating the transfer rates of deleted or non-deleted IncC plasmids and their costs on the recipient strain. Plasmid deletions strongly improved conjugation efficiency with no negative growth effect. Our findings indicate that the flexibility of the MDR-region of the IncC plasmids can promote their dissemination, and provide diverse opportunities to capture new resistance genes. In a broader view, they suggest that the vertical-horizontal transmission tradeoff can be manipulated by the plasmid to improve its fitness.
Mitigation of Stress-induced Structural Remodeling and Functional Deficiency in iPSC-CMs with PLN R9C Mutation by Promoting Autophagy
Authors: Yu Qi , Barndt Robert J , Shen Yawei , Sallam Karim , Tang Ying , Chan Stephen Y. , Wu Joseph C. , Liu Qing , Wu Haodi 
Published: April 2024

AbstractBackgroundPhospholamban (PLN) is a key regulator of cardiac function connecting adrenergic signaling and calcium homeostasis. The R9C mutation of PLN is known to cause early onset dilated cardiomyopathy (DCM) and premature death, yet the detailed mechanisms underlie the pathologic remodeling process are not well defined in human cardiomyocytes. The aim of this study is to unravel the role of PLN R9C in DCM and identify potential therapeutic targets.MethodsPLN R9C knock-in (KI) and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated and comprehensively examined for their expression profile, contractile function, and cellular signaling under both baseline conditions and following functional challenges.ResultsPLN R9C KI iPSC-CMs exhibited near-normal morphology and calcium handling, slightly increased contractility, and an attenuated response to β-adrenergic activation compared to wild-type (WT) cells. However, treatment with a maturation medium (MM) has induced fundamentally different remodeling in the two groups: while it improved the structural integrity and functional performance of WT cells, the same treatment result in sarcomere disarrangement, calcium handling deficiency, and further disrupted adrenergic signaling in PLN R9C KI cells. To understand the mechanism, transcriptomic analysis showed the enrichment of protein homeostasis signaling pathways specifically in PLN R9C KI cells in response to the MM treatment and increased contractile demands. Further studies also indicated elevated ROS levels, interrupted autophagic flux, and increased pentamer PLN aggregation in functionally challenged KI cells. These results were further confirmed in patient-specific iPSC-CM models, suggesting that functional stresses exacerbate the deficiencies in PLN R9C cells through disrupting protein homeostasis. Indeed, treating stressed patient cells with autophagy-accelerating reagents, such as metformin and rapamycin, has restored autophagic flux, mitigated sarcomere disarrangement, and partially rescued β-adrenergic signaling and cardiac function.ConclusionsPLN R9C leads to a mild increase of calcium recycling and contractility. Functional challenges further enhanced contractile and proteostasis stress, leading to autophagic overload, structural remodeling, and functional deficiencies in PLN R9C cardiomyocytes. Activation of autophagy signaling partially rescues these effects, revealing a potential therapeutic target for DCM patients with the PLN R9C mutation.Graphic abstractsA graphic abstract is available for this article.
Ruvbl1 is required for the reproduction of the corn planthopper,Peregrinus maidis
Authors: Xavier César A. D. , Tyson Clara , Whitfield Anna E. 
Published: April 2024

AbstractRuvbl1(also known as TIP49, Pontin) encodes an ATPase of the AAA+ protein superfamily involved in several cellular functions, including chromatin remodeling, control of transcription, and cellular development (motility, growth, and proliferation). Here, we used anin-vivoRNA interference (RNAi) approach to evaluate the effect ofRuvbl1silencing on the physiology of the corn planthopper,Peregrinus maidis. Silencing ofP. maidis Ruvbl1(PmRuvbl1) was correlated with visible morphology changes in female individuals with significant increases in body mass observed at 8 and 12 days after double strand RNA (dsRNA) injection. Ovary morphology was significantly affected in adult females withPmRuvbl1silenced, with no mature oocytes observed at 8 and 12 days after gene silencing. Whereas no significant difference in egg laying was observed 4 days after dsRNA injection, significantly fewer eggs were laid in plants at 8 and 12 days after dsRNA treatment. Furthermore, dramatic reductions in egg hatching were observed at all time points afterPmRuvbl1silencing, compared to dsGFP-injected controls. These results extend PmRuvbl1 functions as a putative regulator ofP. maidisreproduction and demonstrate the potential ofRuvbl1to be further exploited as a target for RNAi-mediated insect control.
A protein condensation network contextualises cell fate decisions
Authors: Peskett Thomas R , Lee Sung Sik , Barral Yves 
Published: April 2024

SummaryFor cells to thrive, they must make appropriate fate decisions based on a myriad of internal and external stimuli. But how do they integrate these different forms of information to contextualise their decisions? Old yeast cells showed an ability to dampen their proliferation as they entered senescence. Conversely, they had an enhanced ability to promote proliferation during escape from pheromone stimulation. A network of nucleoprotein condensation states involving processing bodies (P-bodies) and the prion-like RNA-binding protein, Whi3, controlled these opposing fate decisions. In old but not in young cells, condensation of Whi3 was both necessary and sufficient for senescence entry. In old cells, Whi3 localised to age-dependent P-bodies. Preventing their formation stopped Whi3 condensation from driving senescence entry. Challenging old cells with an external stimulus, pheromone, revealed that the condensates had a second function: potentiating the cell’s ability to trigger escape from the mating pheromone response. These findings identify biomolecular condensation as an integrator of contextual information as cells make decisions, enabling them to navigate overlapping life events.
How digitalization and information technology adoption affect firms' innovation performance: evidence from Chinese automotive firms
Authors: Zhou Fei , Xu Songling 
Published: April 2024

PurposeThis study aims to explore how the application of digital technology and information technology can help firms improve their innovation performance and examines the mediating mechanisms of supply chain agility and supply chain integration.Design/methodology/approachThis study conducted a questionnaire survey of 320 business managers in an automotive cluster in China and analyzed the collected data using structural equations.FindingsDigital technology applications (DTA) have a positive impact on innovation performance, while supply chain agility and integration mediate this impact. In addition, information technology applications (ITA) also has a positive impact on innovation performance, while supply chain agility and integration mediate between the two. Supply chain agility (SCA) and supply chain integration (SCI) significantly enhance the positive impact of technology adoption on firms' innovation performance.Originality/valueThis study confirms the impact of digital technology and information technology applications on innovation performance and explores the mediating role played by supply chain agility and integration.
Maximizing marketing impact: heuristic vs ensemble models for attribution modeling
Authors: Gaur Jitendra , Bharti Kumkum , Bajaj Rahul 
Published: April 2024

Purpose
Allocation of the marketing budget has become increasingly challenging due to the diverse channel exposure to customers. This study aims to enhance global marketing knowledge by introducing an ensemble attribution model to optimize marketing budget allocation for online marketing channels. As empirical research, this study demonstrates the supremacy of the ensemble model over standalone models.

Design/methodology/approach
The transactional data set for car insurance from an Indian insurance aggregator is used in this empirical study. The data set contains information from more than three million platform visitors. A robust ensemble model is created by combining results from two probabilistic models, namely, the Markov chain model and the Shapley value. These results are compared and validated with heuristic models. Also, the performances of online marketing channels and attribution models are evaluated based on the devices used (i.e. desktop vs mobile).

Findings
Channel importance charts for desktop and mobile devices are analyzed to understand the top contributing online marketing channels. Customer relationship management-emailers and Google cost per click a paid advertising is identified as the top two marketing channels for desktop and mobile channels. The research reveals that ensemble model accuracy is better than the standalone model, that is, the Markov chain model and the Shapley value.

Originality/value
To the best of the authors’ knowledge, the current research is the first of its kind to introduce ensemble modeling for solving attribution problems in online marketing. A comparison with heuristic models using different devices (desktop and mobile) offers insights into the results with heuristic models.
The role of organisational culture in university–firm cooperation: multiple case studies
Authors: Sartor de Oliveira Rafael , Franco Mário , Rodrigues Margarida 
Published: April 2024

Purpose
Cooperative agreements between universities and firms (U–F) have gained prominence. However, the literature on organisational culture and the formation of cooperation agreements is scarce. This study aims to analyse, from the perspective of the managers of small- and medium-sized enterprises (SMEs) and those in charge in universities, the perceptions of the influence of organisational culture on this type of U–F cooperation.

Design/methodology/approach
To this end, multiple case studies were adopted, involving cooperation agreements between a Portuguese and eight SMEs incubated in UBImedical. Semi-structured interviews were used to gather information, aiming to understand the meaning, importance and possible obstacles caused by organisational culture in this U–F cooperation agreement.

Findings
Content analysis of the results obtained leads to the conclusion that cultural compatibility is a crucial factor for successful U–F cooperation. The exchange of knowledge, mutual trust and flexibility between those involved are identified as key determinants to build shared norms that allow a more productive, assertive union.

Practical implications
The study represents an important tool to support SME managers and those in charge of universities, as the evidence obtained can help them to define policies and actions with regard to the U–F cooperation process. More precisely, these SME and university managers could give more attention to culture in future cooperation agreements.

Originality/value
This study advances understanding of the role of organisational culture in a cooperation agreement since this was a gap identified in the literature on the topic. It also contributes to the existing body of work on U–F cooperation, demonstrating that organisational culture is considered important by partners in these agreements and should be adjusted towards compatible alignment of each party’s expectations.