bluuebunny/crossref_metadata_2025_split huggingface dataset:
CXCR4 controls movement and degranulation of CD8+T cells in the influenza-infected lung via differential effects on interaction and tissue scanning
Authors: Mrass Paulus , Kinjyo Ichiko , Byrum Janie R. , Torres David , Baker Steven F. , Cannon Judy L. 
Published: September 2022

AbstractEffector CD8+T cell interactions are critical in controlling viral infection by directly killing infected cells but overabundant or sustained activation also exacerbates tissue damage. Chemokines promote the trafficking of effector CD8+T cells into infected tissues, but we know little about how chemokines regulate the function of CD8+T cells within tissues. Using a murine model of influenza A virus infection, we found that expression of the chemokine receptor CXCR4 by lung-infiltrating cytotoxic T cells correlated with the expression of the degranulation marker CD107a. Inhibition of CXCR4 reduced activation, adhesion, and degranulation of cytotoxic T cellsin vitroandin vivo. Moreover, in live influenza-infected lung tissue, T cells stopped moving in lung regions with high levels of influenza antigen, and CXCR4 was essential for CD8+T cells to execute this arrest signal fully. In contrast, CXCR4 increased the motility of CD8+T cells in low-influenza areas of the lung. We also found that CXCR4 stimulated the effector function of lung-infiltrating cytotoxic T cells even after clearance of influenza virus, and inhibition of CXCR4 expedited the recovery of influenza-infected mice, despite delayed clearance of the replication-competent virus. Our results suggest that CXCR4 promotes the interaction strength of cytotoxic T cells in lung tissue through combined effects on T cell movement and interaction with virally infected target cells in influenza infected-lungs.
Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 co-activation
Authors: Shah Viral , Giotopoulos George , Osaki Hikari , Meyerhöfer Markus , Meduri Eshwar , Schubert Benedict , Yun Haiyang , Horton Sarah J , Agrawal-Singh Shuchi , Haehnel Patricia S , Basheer Faisal , Lugo Dave , Kühn Michael WM , Guezguez Borhane , Theobald Matthias , Kindler Thomas , Gallipoli Paolo , Prinjha Rab K , Huntly Brian JP , Sasca Daniel 
Published: September 2022

AbstractInitial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). The main reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. To study mechanisms of resistance, we investigated immediate epigenetic and transcriptional responses following BET inhibition, and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback loop that attenuates inhibition, or even increases expression, of specific transcriptional modules. This adaptation is most marked at key AML maintenance genes and is mediated by p300, suggesting a rational therapeutic opportunity by combining BET- and p300- inhibition. p300 activity is required during all steps of adaptation. However, the transcriptional programs that p300 regulates to induce resistance to BETi differ between AML subtypes. Remarkably, in some AMLs, p300 regulates a series of transitional transcriptional patterns that allow homeostatic adjustments during earlier stages of resistance to BET-inhibitors. In consequence, p300 remains crucial throughout all stages of resistance in sensitive AML-subtypes, although its importance declines following the development of chronic resistance to BET inhibitors in some other AMLs. Altogether, our study elucidates the mechanisms that underlie an “acute” state of resistance to BET inhibition, achieved through p300 activity, and how these mechanisms remodel to become “chronic”. Importantly, however, our data also suggest that a sequential treatment with BET- and p300 inhibition may prevent resistance development, thereby improving outcomes.Key pointsA mechanistic feedback to p300 enables acute tolerance to BET inhibition.p300 regulates transcriptional networks that lead to chronic resistance to BET inhibition.Sequential BET-, followed by p300-inhibition, is synthetically lethal in AML, and is optimally deployed during earlier stages of resistance to BET inhibitors.
Topological Links in Predicted Protein Complex Structures Reveal Limitations of AlphaFold
Authors: Hou Yingnan , Xie Tengyu , He Liuqing , Tao Liang , Huang Jing 
Published: September 2022

AbstractAlphaFold is making great progress in protein structure prediction, not only for single-chain proteins but also for multi-chain protein complexes. When using AlphaFold-Multimer to predict protein–protein complexes, we observed some unusual structures in which chains are looped around each other to form topologically intertwining links at the interface. To our knowledge, such topological links are never observed in the experimental structures deposited in the Protein Data Bank (PDB). Although it is well known and has been well studied that protein structures may have topologically complex shapes such as knots and links, existing methods are hampered by the chain closure problem and show poor performance in identifying topologically linked structures in protein–protein complexes. Therefore, we address the chain closure problem by using sliding windows from a local perspective and propose an algorithm to measure the topological–geometric features that can be used to identify topologically linked structures. An application of the method to AlphaFold-Multimer-predicted protein complex structures finds that approximately 0.7% of the predicted structures contain topological links. The method presented in this work will facilitate the computational study of protein–protein interactions and help further improve the structural prediction of multi-chain protein complexes.
Complete blood count and selected serum parameters of Venus transgenic rabbits
Authors: Biró Bálint , Skoda Gabriella , Hoffmann Orsolya Ivett , Hiripi László , Gócza Elen , Lipták Nándor 
Published: September 2022

AbstractGreen fluorescent protein (GFP) transgenic laboratory animals (mice, rats, rabbits etc.) are commonly used in basic research for modelling human diseases, studying organ development, cell transfer during pregnancy or tissue engineering. The expression of the fluorescent protein can be either ubiquitous or tissue-specific, depending on the transgenic construct and the integration site of the transgene. Despite the wide applications, the data about the physiological parameters of GFP transgenic animals are limited. In most of the transgenic lines, GFP does not induce any detrimental effect, but GFP-induced conditions are also reported. Altered T-lymphopoiesis and low white blood cell (WBC) count were observed in human ubiquitin C promoter-driven GFP transgenic (UBC-GFP) mice due to latent stem cell defect. The aim of the present study was to examine the effects of the Venus fluorescent protein on hematopoiesis and general health of transgenic rabbits, thus, hematology along with selected serum parameters were measured.
Restoring functional D2- to D1-neuron correspondence enables goal-directed action control in long-lived striatal circuits
Authors: Bertran-Gonzalez Jesus , Dinale Caroline , Matamales Miriam 
Published: September 2022

AbstractMultidisciplinary evidence suggests that instrumental performance is governed by two major forms of behavioural control: goal-directed and autonomous processes. Brain-state abnormalities affecting the striatum, such as ageing, often shift control towards autonomous—habit-like—behaviour, although the neural mechanisms responsible for this shift remain unknown. Here, combining instrumental conditioning with cell-specific functional mapping and manipulation in striatal neurons, we explored strategies that invigorate goal-directed action capacity in aged mice. In animals performing instrumental actions, D2- and D1-neurons of the aged striatum were engaged in a characteristically counterbalanced manner, something that related to the propensity to express autonomous behaviour. Long-lasting, cell-specific desensitisation of D2-neurons in aged transgenic mice recapitulated the uneven D2-to D1-neuron functional correspondence observed in young mice, an effect that enabled successful goal-directed action. Our findings contribute to the understanding of the neural bases of behavioural control and propose neural system interventions that enhance cognitive functioning in habit-prone brains.
Self-supervised deep learning for pan-cancer mutation prediction from histopathology
Authors: Saldanha Oliver Lester , Loeffler Chiara M. L. , Niehues Jan Moritz , van Treeck Marko , Seraphin Tobias P. , Hewitt Katherine Jane , Cifci Didem , Veldhuizen Gregory Patrick , Ramesh Siddhi , Pearson Alexander T. , Kather Jakob Nikolas 
Published: September 2022

AbstractThe histopathological phenotype of tumors reflects the underlying genetic makeup. Deep learning can predict genetic alterations from tissue morphology, but it is unclear how well these predictions generalize to external datasets. Here, we present a deep learning pipeline based on self-supervised feature extraction which achieves a robust predictability of genetic alterations in two large multicentric datasets of seven tumor types.
Widely Distributed Biosynthetic Cassette Is Responsible for Diverse Plant Side-Chain-Cross-Linked Cyclopeptides
Authors: Lima Stella T. , Ampolini Brigitte G. , Underwood Ethan B. , Graf Tyler N. , Earp Cody E. , Khedi Imani C. , Chekan Jonathan R. 
Published: September 2022

AbstractCyclopeptide alkaloids are an abundant class of plant cyclopeptides with over 200 analogs described and bioactivities ranging from analgesic to antiviral. While these natural products have been known for decades, their biosynthetic basis remains unclear. Using a transcriptome-mining approach, we link the cyclopeptide alkaloids from Ceanothus americanus to dedicated RiPP precursor peptides and identify new, widely distributed split BURP-domain containing gene clusters. Precursor peptides from these biosynthetic cassettes directly map to both cyclopeptide alkaloids from Ziziphus jujuba and the structurally distinct hibispeptins from Hibiscus syriacus. Guided by our bioinformatic analysis, we identify and isolate new cyclopeptides from Coffea arabica, which we named arabipeptins. These results expand our understanding of the biosynthetic pathways responsible for diverse plant side chain cross-linked cyclopeptides and suggest the presence of previously unknown natural products or protein post-translational modifications that are widely distributed in eudicots.
SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion
Authors: Christ Wanda , Kapell Sebastian , Sobkowiak Michal J. , Mermelekas Georgios , Evertsson Björn , Sork Helena , Saher Osama , Bazaz Safa , Gustafsson Oskar , Cardenas Eduardo I. , Villa Viviana , Ricciarelli Roberta , Sandberg Johan K. , Bergquist Jonas , Sturchio Andrea , Svenningsson Per , Malm Tarja , Espay Alberto J. , Pernemalm Maria , Lindén Anders , Klingström Jonas , El Andaloussi Samir , Ezzat Kariem 
Published: September 2022

AbstractThe corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed the interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogenous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as: APLP1 (amyloid beta precursor like protein 1), ApoE, clusterin, α2-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Additionally, viral amyloid induction led to a dramatic drop in the soluble protein concentration in the CSF. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF and result in soluble protein depletion, and thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.Significance StatementViruses have generally been excluded from the etiology of amyloid pathologies based on the assumption that amyloid formation requires a proteinaceous conformational template (a prion) to form. Here we show that neuroinvasive viruses induce amyloid aggregation of a plethora of proteins in human CSF even after UV inactivation. Our work illustrates that viruses can induce amyloid aggregation of endogenous human proteins in their native environment by acting as physical catalysts of amyloid nucleation and phase transition. Demonstrating this direct mechanistic link, which is independent of templating, can help better understand the link between viruses and neurodegenerative disorders, especially in the post-COVID-19 era.
Genome characterization of monkeypox cases detected in India: Identification of three sub clusters among A.2 lineage
Authors: Shete Anita M. , Yadav Pragya D. , Kumar Abhinendra , Patil Savita , Patil Deepak Y. , Joshi Yash , Majumdar Triparna , Relhan Vineet , Sahay Rima R. , Vasu Meenakshy , Gawande Pranita , Verma Ajay , Kumar Arbind , Dhakad Shivram , Krishnan Anukumar Bala , Chenayil Shubin , Kumar Suresh , Abraham Priya 
Published: September 2022

AbstractSince May 2022, Monkeypox, a zoonotic Orthopox DNA virus was reported in more than 102 countries indicating expansion of its geographic range. We analyzed the complete genomes sequences of Monkeypox cases from Kerala (n=5 travelled from UAE) and Delhi (n=5 no travel history), India confirmed during July to August 2022. All the retrieved MPXV sequences from India covering 90 to 99% genome belong to A.2 lineage of clade IIb. The A.2 MPXV lineage divided in three sub clusters; first cluster Kerala n=5, Delhi n=2 aligned with the USA-2022 ON674051.1; while second of Delhi n=3 aligned with USA-2022 ON675438.1 and third consists of the UK, USA and Thailand. Recent update in MPXV lineage designated all the five sequences from Kerala as A.2.1. In addition to known 16 single nucleotide polymorphisms (SNPs) along with 13 APOBEC3 cytosine deaminase activity determined specific lineage defining mutations in A.2 lineage, 25 additional APOBEC3 mutations were found in 10 reported sequences. The study emphasizes need of enhancing genomic surveillance to understand the mutation and its linkage.
A highly contiguous genome assembly of red perilla (Perilla frutescens) domesticated in Japan
Authors: Tamura Keita , Sakamoto Mika , Tanizawa Yasuhiro , Mochizuki Takako , Matsushita Shuji , Kato Yoshihiro , Ishikawa Takeshi , Okuhara Keisuke , Nakamura Yasukazu , Bono Hidemasa 
Published: September 2022

AbstractPerilla frutescens(Lamiaceae) is an important herbal plant with hundreds of bioactive chemicals, among which perillaldehyde and rosmarinic acid are the two major bioactive compounds in the plant. The leaves of red perilla are used as traditional Kampo medicine or food ingredients. However, the medicinal and nutritional uses of this plant could be improved by enhancing the production of valuable metabolites through the manipulation of key enzymes or regulatory genes using genome editing technology. Here, we generated a high-quality genome assembly of red perilla domesticated in Japan. A near-complete chromosome level assembly ofP. frutescenswas generated contigs with N50 of 41.5 Mb from PacBio HiFi reads. 99.2% of the assembly was anchored into 20 pseudochromosomes, among which seven pseudochromosomes consisted of one contig, while the rest consisted of less than six contigs. Gene annotation and prediction of the sequences successfully predicted 86,258 gene models, including 76,825 protein-coding genes. Further analysis showed that potential targets of genome editing for the engineering of anthocyanin pathways inP. frutescensare located on the late-stage pathways. Overall, our genome assembly could serve as a valuable reference for selecting target genes for genome editing ofP. frutescens.
Corrosion behavior research and corrosion prediction of structural steel in marine engineering
Authors: Cao Hang , Wang Kangchen , Song Shenyou , Zhang Xiaohu , Gao Qianyu , Liu Yuanyuan 
Published: September 2022

Purpose
This paper aims to reveal the corrosion mechanism and corrosion development regulation of marine engineering structural steel in the marine environment and provide constructive suggestions for marine immersed tunnel engineering.

Design/methodology/approach
In this study, marine engineering structural steel’s behavior and corrosion prediction were carried out under the conditions of no cathodic protection and under-protection by artificially adding dissolved oxygen in a simulated seawater solution as a depolarizing agent.

Findings
Marine resources are rich in China. With the development of the economy and the improvement of engineering technology, marine engineering structural steel is used more and more widely. Engineering structural steel has a great risk of corrosion failure for long-term service in seawater, as seawater is a kind of corrosive medium containing various salts. At present, there are few projects and research studies available on the corrosion in the seawater environment of Q390C engineering structural steel, which is used in the Shenzhen–Zhongshan Link immersed tunnel steel shell at home and abroad. It cannot guide the corrosion of immersed tunnel steel shells in the ocean.

Originality/value
In this paper, the corrosion mechanism and corrosion development regulation of marine engineering structural steel in the marine environment are studied by accelerated corrosion test in the laboratory, which is of great significance to ensure the long-life durability of the immersed tunnel in marine engineering.
Modelling coastal externalities effects on residential housing values
Authors: Ayoola Adeyosoye Babatunde , Oladapo Adejoke Rashidat , Ojo Babajide , Oyetunji Abiodun Kolawole 
Published: September 2022

Purpose
This paper aims to examine the impact of coastline on the rental value of residential property in proximity to the coastline, using the hedonic pricing model from two perspectives. First, Model 1A–C accounted for estimating the influence of coastal amenities while controlling for other housing attributes influencing rent. Second, Model 2A–C accounted for the interaction between coastal amenities/disamenities and other housing attributes influencing rent.

Design/methodology/approach
A survey approach was adopted for the data collection process. For both models, property values were measured in proximity to coastline using 0–250 m, 251–500 m and 0–500 m.

Findings
Findings revealed that property rental value increases as we move away from the coastline when disamenities are not controlled. The results suggested that for a mean-priced home (N2,941,029 or $8,170) at the mean distance from the coastline (301.83 m), a 1% increase in distance from the coastline would result in a 0.001% or N9.77 ($0.03) increase in rental value.

Practical implications
The implication to real estate valuers is that varying premiums should be considered when valuing a property depending on the distance to the coastline while considering other housing attributes.

Originality/value
This research introduces a novel approach to the hedonic model for determining property values in proximity to coastal environment by estimating the influence of coastal amenities while controlling for other housing attributes influencing rent, on the one hand, and accounting for the interaction between coastal amenities/disamenities and other housing attributes influencing rent, on the other.
Coaching for change: redefining the concept of change within a practice-based coaching model
Authors: Stoetzel Lindsay , Taylor-Marshall Sandra 
Published: September 2022

PurposeAcross K–12 settings, instructional coaching continues to flourish as an approach to teacher professional development intended to address long-standing inequities in student achievement. Yet, coaching models differ in how to conceptualize change or transformation as a result of coaching efforts.Design/methodology/approachThis case study problematizes the concept of change within one practice-based coaching program, by positing the possibilities of striving for transformational change directed at addressing educational inequities.FindingsQualitative methods reveal how coaching belief statements guide the burgeoning identities of beginning coaches to align to (and at times extend beyond) coaching for change through the lens of teacher practice.Practical implicationsImplications describe ways that coaching programs might utilize reflection and analysis activities to foster more equity-oriented coaching identities, regardless of coaching model.Originality/valueDesigning and facilitating authentic learning opportunities for coaches to reflect, rehearse, connect, and apply knowledge to practice as they develop their own understanding of what it means to coach for change is crucial.
Innovative approach and marketing skill: a case study of artisan entrepreneurs of India
Authors: Meera S. , Vinodan A. 
Published: September 2022

Purpose
This study aims to examine individual-specific market orientation as an innovative approach and its relationship with marketing skills among artisan entrepreneurs in India.

Design/methodology/approach
The study adopted an in-depth interview to explore variables, a questionnaire survey to understand their latent dimensions through exploratory factor analysis and structural equation modeling to test the relationship between constructs under study.

Findings
The interview result indicates that 20 variables explain factors affecting individual-specific market orientation with four latent dimensions: customer orientation, competitor orientation, external coordination orientation and personal selling orientation. There is a significant and positive relationship between customer orientation and personal selling orientation with the marketing skills of artisan entrepreneurs in India.

Research limitations/implications
The study is confined to three southern states of India and weaving villages known for their endemic product specifications.

Practical implications
The study found significance in orienting artisan entrepreneurs of developing countries and equipping them with desired skills to meet the changing dynamics of the market and meet their livelihood needs. The study further supports policymaking in strengthening the capability of artisans to enter the market without mediators.

Social implications
The model provides insight into other unorganized sectors to formulate innovative approaches to strengthen marketing skills and entrepreneurial ability.

Originality/value
As an exploratory study, examining individual-level market orientation as an innovative approach and their relationship with marketing skills among artisan entrepreneurs was unexplored in several unorganized sectors, including handlooms.