bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitope-anchored contrastive transfer learning for paired CD8+T cell receptor-antigen recognition
Authors: Zhang Yumeng , Wang Zhikang , Jiang Yunzhe , Littler Dene R , Gerstein Mark , Purcell Anthony W , Rossjohn Jamie , Ou Hong-Yu , Song Jiangning
Published: April 2024

Understanding the mechanisms of T-cell antigen recognition that underpin adaptive immune responses is critical for the development of vaccines, immunotherapies, and treatments against autoimmune diseases. Despite extensive research efforts, the accurate identification of T cell receptor (TCR)-antigen binding pairs remains a significant challenge due to the vast diversity and cross-reactivity of TCRs. Here, we propose a deep-learning framework termed Epitope-anchored Contrastive Transfer Learning (EPACT) tailored to paired human CD8+TCRs from single-cell sequencing data. Harnessing the pre-trained representations and the contrastive co-embedding space, EPACT demonstrates state-of-the-art model generalizability in predicting TCR binding specificity for unseen epitopes and distinct TCR repertoires, offering potential values for practical outcomes in real-world scenarios. The contrastive learning paradigm achieves highly precise predictions for immunodominant epitopes and facilitates interpretable analysis of epitope-specific T cells. The TCR binding strength predicted by EPACT aligns well with the surge in spike-specific immune responses targeting SARS-CoV-2 epitopes after vaccination. We further fine-tune EPACT on TCR-epitope structural data to decipher the residue-level interactions involved in T-cell antigen recognition. EPACT not only exhibits superior capabilities in quantifying inter-chain distance matrices and identifying contact residue pairs but also corroborates the presence of molecular mimicry across multiple tumor-associated antigens. Together, EPACT can serve as a useful AI approach with significant potential in practical applications and contribute toward the development of TCR-based diagnostics and immunotherapies.
Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology
Authors: Takemae Nobuhiro , Kuba Yumani , Oba Kunihiko , Kageyama Tsutomu
Published: April 2024

The use of metagenomic next-generation sequencing technology to obtain complete viral genome sequences directly from clinical samples with low viral load remains challenging—especially in the case of respiratory viruses—due to the low copy number of viral versus host genomes. To overcome this limitation, target capture sequencing for the enrichment of specific genomes has been developed and applied for direct genome sequencing of viruses. However, as the efficiency of enrichment varies depending on the probes, the type of clinical sample, etc., validation is essential before target capture sequencing can be applied to clinical diagnostics. Here we evaluated the utility of target capture sequencing with a comprehensive viral probe panel for clinical respiratory specimens collected from patients diagnosed with SARS-CoV-2 or influenza type A. We focused on clinical specimens containing low copy numbers of viral genomes. Target capture sequencing yielded approximately 180- and 2000-fold higher read counts of SARS-CoV-2 and influenza A virus, respectively, than metagenomic sequencing when the RNA extracted from specimens contained 59.3 copies/µL of SARS-CoV-2 or 544 copies/µL of influenza A virus, respectively. In addition, the target capture sequencing identified sequence reads in all SARS-CoV-2- or influenza type A-positive specimens with <26 RNA copies/µL, some of which also yielded >70% of the full-length genomes of SARS-CoV-2 or influenza A virus. Furthermore, the target capture sequencing using comprehensive probes identified co-infections with viruses other than SARS-CoV-2, suggesting that this approach will not only detect a wide range of viruses, but also contribute to epidemiological studies.
A Deep Learning-Driven Sampling Technique to Explore the Phase Space of an RNA Stem-Loop
Authors: Gupta Ayush , Ma Heng , Ramanathan Arvind , Zerze Gül H.
Published: April 2024

The folding and unfolding of RNA stem-loops are critical biological processes; however, their computational studies are often hampered by the ruggedness of their folding landscape, necessitating long simulation times at the atomistic scale. Here, we adapted DeepDriveMD (DDMD), an advanced deep learning-driven sampling technique originally developed for protein folding, to address the challenges of RNA stem-loop folding. Although tempering- and order parameter-based techniques are commonly used for similar rare event problems, the computational costs and/or the need fora prioriknowledge about the system often present a challenge in their effective use. DDMD overcomes these challenges by adaptively learning from an ensemble of running MD simulations using generic contact maps as the raw input. DeepDriveMD enables on-the-fly learning of a low-dimensional latent representation and guides the simulation toward the undersampled regions while optimizing the resources to explore the relevant parts of the phase space. We showed that DDMD estimates the free energy landscape of the RNA stem-loop reasonably well at room temperature. Our simulation framework runs at a constant temperature without external biasing potential, hence preserving the information of transition rates, with a computational cost much lower than that of the simulations performed with external biasing potentials. We also introduced a reweighting strategy for obtaining unbiased free energy surfaces and presented a qualitative analysis of the latent space. This analysis showed that the latent space captures the relevant slow degrees of freedom for the RNA folding problem of interest. Finally, throughout the manuscript, we outlined how different parameters are selected and optimized to adapt DDMD for this system. We believe this compendium of decision-making processes will help new users adapt this technique for the rare-event sampling problems of their interest.
Leveraging Large Language Models to Analyze Continuous Glucose Monitoring Data: A Case Study
Authors: Healey Elizabeth , Tan Amelia , Flint Kristen , Ruiz Jessica , Kohane Isaac
Published: April 2024

Continuous glucose monitors (CGM) provide patients and clinicians with valuable insights about glycemic control that aid in diabetes management. The advent of large language models (LLMs), such as GPT-4, has enabled real-time text generation and summarization of medical data. Further, recent advancements have enabled the integration of data analysis features in chatbots, such that raw data can be uploaded and analyzed when prompted. Studying both the accuracy and suitability of LLM-derived data analysis performed on medical time series data, such as CGM data, is an important area of research. The objective of this study was to assess the strengths and limitations of using an LLM to analyze raw CGM data and produce summaries of 14 days of data for patients with type 1 diabetes. This study used simulated CGM data from 10 different cases. We first evaluated the ability of GPT-4 to compute quantitative metrics specific to diabetes found in an Ambulatory Glucose Profile (AGP). Then, using two independent clinician graders, we evaluated the accuracy, completeness, safety, and suitability of qualitative descriptions produced by GPT-4 across five different CGM analysis tasks. We demonstrated that GPT-4 performs well across measures of accuracy, completeness, and safety when producing summaries of CGM data across all tasks. These results highlight the capabilities of using an LLM to produce accurate and safe narrative summaries of medical time series data. We highlight several limitations of the work, including concerns related to how GPT-4 may misprioritize highlighting instances of hypoglycemia and hyperglycemia. Our work serves as a preliminary study on how generative language models can be integrated into diabetes care through CGM analysis, and more broadly, the potential to leverage LLMs for streamlined medical time series analysis.
Network localization of pediatric lesion-induced dystonia
Authors: Gelineau-Morel Rose , Dlamini Nomazulu , Bruss Joel , Cohen Alexander Li , Robertson Amanda , Alexopoulos Dimitrios , Smyser Christopher D. , Boes Aaron D.
Published: April 2024

Objective

Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia.

Methods

Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia.

Results

Multivariate lesion-symptom mapping showed that lesions of the putamen (stroke: r = 0.50, p <0.01; hypoxia, r = 0.64, p <0.001) and globus pallidus (kernicterus, r = 0.61, p <0.01) were associated with dystonia. Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular and somato-cognitive-action networks.

Interpretation

We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is involved in higher order coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention.
Single-cell image-based genetic screens systematically identify regulators of Ebola virus subcellular infection dynamics
Authors: Carlson Rebecca J. , Patten J.J. , Stefanakis George , Soong Brian Y. , Radhakrishnan Adityanarayanan , Singh Avtar , Thakur Naveen , Amarasinghe Gaya K. , Hacohen Nir , Basler Christopher F. , Leung Daisy , Uhler Caroline , Davey Robert A. , Blainey Paul C.
Published: April 2024

Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied image-based screening of a genome-wide CRISPR library to systematically identify host cell regulators of Ebola virus infection in 39,085,093 million single cells. Measuring viral RNA and protein levels together with their localization in cells identified over 998 related host factors and provided detailed information about the role of each gene across the virus replication cycle. We trained a deep learning model on single-cell images to associate each host factor with predicted replication steps, and confirmed the predicted relationship for select host factors. Among the findings, we showed that the mitochondrial complex III subunit UQCRB is a post-entry regulator of Ebola virus RNA replication, and demonstrated that UQCRB inhibition with a small molecule reduced overall Ebola virus infection with an IC50 of 5 μM. Using a random forest model, we also identified perturbations that reduced infection by disrupting the equilibrium between viral RNA and protein. One such protein, STRAP, is a spliceosome-associated factor that was found to be closely associated with VP35, a viral protein required for RNA processing. Loss of STRAP expression resulted in a reduction in full-length viral genome production and subsequent production of non-infectious virus particles. Overall, the data produced in this genome-wide high-content single-cell screen and secondary screens in additional cell lines and related filoviruses (MARV and SUDV) revealed new insights about the role of host factors in virus replication and potential new targets for therapeutic intervention.
In vivoproperties of Arabidopsis FCA condensates involved in RNA 3’ processing
Authors: Jang Geng-Jen , Payne-Dwyer Alex L. , Maple Robert , Wu Zhe , Liu Fuquan , Lopez Sergio G. , Wang Yanning , Fang Xiaofeng , Leake Mark C. , Dean Caroline
Published: April 2024

Our understanding of the functional requirements underpinning biomolecular condensationin vivois still relatively poor. The Arabidopsis RNA binding protein FCA is found in liquid-like nuclear condensates that function in transcription termination, promoting proximal polyadenylation at many targets in the Arabidopsis genome. To further understand the properties of these condensatesin vivowe used single particle tracking experiments on FCA reporters stably expressed at endogenous levels in plant nuclei. These revealed FCA forms a core oligomer of ∼4 molecules that multimerizes into higher-order particles. This assembles into macromolecular condensates through the function of the coiled-coil protein FLL2, which is genetically required for FCA function. FLL2 predominately co-localizes with FCA in larger sized condensates. A missense mutation in the FCA RRM domain, also genetically required for FCA function, reduced both average FCA particle and condensate size but did not perturb the core oligomer. Our work points to a modular structure for FCA condensates involving multimerization of core oligomers that assemble into functional macromolecular condensates via associated RNA and FLL2 interactions.
Automated microscopic measurement of fibrinaloid microclots and their degradation by nattokinase, the main natto protease
Authors: Grixti Justine M. , Theron Chrispian W. , Salcedo-Sora J. Enrique , Pretorius Etheresia , Kell Douglas B.
Published: April 2024

Nattokinase, from the Japanese fermented food natto, is a protease with fibrinolytic activity that can thus degrade conventional blood clots. In some cases, however, including in Long COVID, fibrinogen can polymerise into an anomalous amyloid form to create clots that are resistant to normal fibrinolysis and that we refer to as fibrinaloid microclots. These can be detected with the fluorogenic stain thioflavin T. We describe an automated microscopic technique for the quantification of fibrinaloid microclot formation, which also allows the kinetics of their formation and aggregation to be recorded. We also here show that recombinant nattokinase is effective at degrading the fibrinaloid microclotsin vitro. This adds to the otherwise largely anecdotal evidence, that we review, that nattokinase might be anticipated to have value as part of therapeutic treatments for individuals with Long COVID and related disorders that involve fibrinaloid microclots.
Associations between structural brain changes and blood neurofilament light chain protein in treatment-resistant schizophrenia
Authors: Cilia Brandon-Joe , Eratne Dhamidhu , Wannan Cassandra , Malpas Charles , Janelidze Shorena , Hansson Oskar , Everall Ian , Bousman Chad , Thomas Naveen , Santillo Alexander F , Velakoulis Dennis , Pantelis Christos
Published: April 2024

Background and Hypothesis

Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia; TRS). While abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often observed in schizophrenia, it is anticipated that biomarkers of neuronal injury like neurofilament light chain protein (NfL) can improve our understanding of the pathological basis underlying schizophrenia. The current study aimed to determine whether people with TRS demonstrate different associations between plasma NfL levels and regional cortical thickness reductions compared with controls.

Study Design

Measurements of plasma NfL and cortical thickness were obtained from 39 individuals with TRS, and 43 healthy controls. T1-weighted magnetic resonance imaging sequences were obtained and processed via FreeSurfer. General linear mixed models adjusting for age and weight were estimated to determine whether the interaction between diagnostic group and plasma NfL level predicted lower cortical thickness across frontotemporal structures and the insula.

Study Results.

Significant (false discovery rate corrected) cortical thinning of the left (p= 0.001,η2p= 0.104) and right (p< 0.001,η2= 0.167) insula was associated with higher levels of plasma NfL in TRS, but not in healthy controls.

Conclusions.

The association between regional thickness reduction of the insula bilaterally and plasma NfL may reflect a neurodegenerative process during the course of TRS. The findings of the present study suggest that some level of cortical degeneration localised to the bilateral insula may exist in people with TRS, which is not observed in the normal population.
Transcriptome landscape of high and low responders to an inactivated COVID-19 vaccine after 4 months using single-cell sequencing
Authors: Zhu Zhongyi , Huang Yaling , Sun Jiatong , Li Meirong , Chen Yong , Zhang Lei , Huang Fubaoqian , Liu Chuanyu , Chen Weijun , Ma Jinmin
Published: April 2024

Background

Variability in antibody responses among individuals following vaccination is a universal phenomenon. Single-cell transcriptomics offers a potential avenue to understand the underlying mechanisms of these variations and improve our ability to evaluate and predict vaccine effectiveness.

Objective

This study aimed to explore the potential of single-cell transcriptomic data in understanding the variability of antibody responses post-vaccination and its correlation with transcriptomic changes.

Methods

Blood samples were collected from 124 individuals on day 21 post COVID-19 vaccination. These samples were categorized based on antibody titers (high, medium, low). On day 135, PBMCs from 27 donors underwent single-cell RNA sequencing to depict the transcriptome atlas.

Results

Differentially expressed genes (DEGs) affecting antibody expression in various cell types were identified. We found that innate immunity, B cell, and T cell population each had a small set of common DEGs (MT-CO1, HLA-DQA2, FOSB, TXNIP, and JUN), and Macrophages and Th1 cells exhibited the largest number of DEGs. Pathway analysis highlighted the dominant role of the innate immune cell population in antibody differences among populations, with a significant impact from the interferon pathway. Furthermore, protein complexes analysis revealed that alterations in the ribosome complex, primarily regulated by DC cells, may play a crucial role in regulating antibody differences. Combining these findings with previous research we proposed a potential regulatory mechanism model of DC cells on B cell antibody production.

Conclusion

While direct prediction of specific antibody levels using single-cell transcriptomic data remains technically and data-wise challenging, our study demonstrated the vast potential of single-cell transcriptomics in understanding the mechanisms underlying antibody responses induced by vaccines.
Negative selection allows human primary fibroblasts to tolerate high somatic mutation loads induced by N-ethyl-N-nitrosourea
Authors: Heid Johanna , Cutler Ronald , Sun Shixiang , Lee Moonsook , Maslov Alexander Y. , Dong Xiao , Sidoli Simone , Vijg Jan
Published: April 2024

Single-cell sequencing has shown that thousands of mutations accumulate with age in most human tissues. While there is ample evidence that some mutations can clonally amplify and lead to disease, the total burden of mutations a cell tolerates without functional decline remains unknown. Here we addressed this question by exposing human primary fibroblasts to multiple, low doses of N-ethyl-N-nitrosourea (ENU) and analyzed somatic mutation burden using single-cell whole genome sequencing. The results indicate that individual cells can sustain ∼60,000 single-nucleotide variants (SNVs) with only a slight adverse effect on growth rate. We provide evidence that such high levels of mutations are only tolerated through negative selection against variants in gene coding regions, and in sequences associated with genetic pathways for maintaining basic cellular function and growth. Since most tissues in adults are non-dividing, these results suggest that somatic mutations in the absence of negative selection may have functionally adverse effects.
Comparative genomics of macaques and integrated insights into genetic variation and population history
Authors: Zhang Shilong , Xu Ning , Fu Lianting , Yang Xiangyu , Li Yamei , Yang Zikun , Feng Yu , Ma Kaiyue , Jiang Xinrui , Han Junmin , Hu Ruixing , Zhang Lu , de Gennaro Luciana , Ryabov Fedor , Meng Dan , He Yaoxi , Wu Dongya , Yang Chentao , Paparella Annalisa , Mao Yuxiang , Bian Xinyan , Lu Yong , Antonacci Francesca , Ventura Mario , Shepelev Valery A. , Miga Karen H. , Alexandrov Ivan A. , Logsdon Glennis A. , Phillippy Adam M. , Su Bing , Zhang Guojie , Eichler Evan E. , Lu Qing , Shi Yongyong , Sun Qiang , Mao Yafei
Published: April 2024

The crab-eating macaques (Macaca fascicularis) and rhesus macaques (M. mulatta) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is ∼42% lower, while centromeres are ∼3.7 times longer than those in humans. The characterization of ∼2 Mbp fixed genetic variants and ∼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g.,CYP2C76andEHBP1L1). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g.,PNPO). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g.,FOLH1andPIEZO2). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g.,STAB1,SEMA3F, andHOXD13). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.
Arabidopsis ubiquitin ligase PUB41 is a positive regulator of the ABA response
Authors: Sharma Avinash , Goldfarb Shalev , Raveh Dina , Bar-Zvi Dudy
Published: April 2024

Seed germination is a highly controlled developmental process. Prevention of early germination is essential to avoid germination at a time that is not likely to allow the completion of the plant life cycle before entering unfavorable seasons. The plant hormone ABA is the key regulator of seed dormancy and inhibition of germination. ABA is also involved in the plant response to drought. Here we report on the involvement of AtPUB41, a U-BOX E3 ubiquitin ligase fromArabidopsis thaliana, in regulating ABA signaling, seed dormancy, germination, and drought resilience.AtPUB41is expressed in most plant vegetative and reproductive tissues. AtPUB41 protein is localized in the cytosol and nucleus.pub41T-DNA insertion mutants display reduced seed dormancy, and their germination is less inhibited by exogenous ABA than seeds of wild-type plants.pub41mutant plants are also hypersensitive to drought. ABA inducesAtPUB41promoter activity and steady-state mRNA levels in the roots. Our data suggest thatAtPUB41is a positive regulator of ABA signaling.

Main Conclusion

Arabidopsis ubiquitin ligase PUB41 is induced by ABA and acts as a positive regulator of ABA signaling by modulating seed dormancy, germination, and drought resilience.
Unveiling Ageing-Associated and Caloric Restriction-Associated Changes in miRNA Expression in Rat Skeletal Muscle and the Mechanisms Mediating their Effects on Muscle Cell Function
Authors: Altab Gulum , Merry Brian J. , Beckett Charles W. , Raina Priyanka , Soriano-Arroquia Ana , Zhang Bruce , Vasilaki Aphrodite , Goljanek-Whysall Katarzyna , de Magalhães João Pedro
Published: April 2024

The mechanisms underlying skeletal muscle ageing, whilst poorly understood, are thought to involve dysregulated micro (mi)RNA expression. Using young and aged rat skeletal muscle tissue, we applied high-throughput RNA sequencing to comprehensively study alterations in miRNA expression occurring with age, as well as the impact of caloric restriction (CR) on these changes. Furthermore, the function of the proteins targeted by these age- and CR-associated miRNAs was ascertained.

Numerous known and novel age-associated miRNAs were identified of which CR normalised 45.5% to youthful levels. Our results suggested miRNAs upregulated with age to downregulated proteins involved in muscle tissue development and metabolism, as well as longevity pathways, such as AMPK and autophagy. Furthermore, our results found miRNAs downregulated with age to upregulate pro-inflammatory proteins, particularly those involved in innate immunity and the complement and coagulation cascades. Interestingly, CR was particularly effective at normalising miRNAs upregulated with age, rescuing their associated protein coding genes but was less effective at rescuing anti-inflammatory miRNAs downregulated with age.

Lastly, the effects of a specific miRNA, miR-96-5p, identified by our analysis to be upregulated with age, were studied in culture C2C12 myoblasts. We demonstrated miR-96-5p to decrease cell viability and markers of mitochondrial biogenesis, myogenic differentiation and autophagy. Overall, our results provide useful information regarding how miRNA expression changes in skeletal muscle, as well as the consequences of these changes and how they are ameliorated by CR.
The BLM-TOP3A-RMI1-RMI2 proximity map reveals that RAD54L2 suppresses sister chromatid exchanges
Authors: Ho Jung Jennifer , Cheng Edith , Wong Cassandra J. , St-Germain Jonathan R. , Dunham Wade H. , Raught Brian , Gingras Anne-Claude , Brown Grant W.
Published: April 2024

Homologous recombination is a largely error-free DNA repair mechanism conserved across all domains of life and is essential for the maintenance of genome integrity. Not only are the mutations in homologous recombination repair genes probable cancer drivers, some also cause genetic disorders. In particular, mutations in the Bloom (BLM) helicase cause Bloom Syndrome, a rare autosomal recessive disorder characterized by increased sister chromatid exchanges and predisposition to a variety of cancers. The pathology of Bloom Syndrome stems from the impaired activity of the BLM-TOP3A-RMI1-RMI2 (BTRR) complex which suppresses crossover recombination to prevent potentially deleterious genome rearrangements. We provide a comprehensive BTRR proximity interactome, revealing proteins that suppress crossover recombination. We find that RAD54L2, a SNF2-family protein, physically interacts with BLM and suppresses sister chromatid exchanges. RAD54L2 is important for recruitment of BLM to chromatin and requires an intact ATPase domain to promote non-crossover recombination. Thus, the BTRR proximity map identifies a regulator of recombination.
Study of the hepatotoxicity of trans-coric acid isolated fromScutellaria baicalensisinin vivoexperiments
Authors: Mikhailovna Fedorova Anastasia , Dmitrievna Vesnina Anna , Sergeevna Milentyeva Irina , Yuryevich Prosekov Alexander
Published: April 2024

Biologically active supplements (BAS) based on plant material, possessing a wide range of beneficial properties (antioxidant, anti-inflammatory, antimicrobial, etc.), are becoming increasingly popular worldwide. Such supplements are readily available and can be used without consulting a healthcare professional. Consequently, the extent of their use is underestimated by doctors. Plant hepatotoxicity is not uncommon, but the frequency and manifestation are not sufficiently characterized. This study is dedicated to investigating the hepatotoxicity of trans-coric acid isolated from the root culture ofScutellaria baicalensisinin vivoexperiments. This work aims to evaluate the hepatotoxicity of trans-coric acid on male rats at doses of 50.0 and 100.0 mg/kg. During the experiment, it was found that trans-coric acid, isolated from the root culture extract ofScutellaria baicalensis, does not induce hepatotoxicity in the presented doses in model animals with 14-day intragastric administration. Thus, this study demonstrates that trans-coric acid can be safely used as a component of BAS for the prevention of chronic diseases, thereby promoting healthy aging.
Modulation of photosystem II heterogeneity and stomatal functioning contribute to sustaining photochemistry and photoprotection in mangroves exposed to a cold wave
Authors: Sebastian John Sunoj. V. , Mathur Sonal , Elsheery Nabil. I. , Yan Li , Lambers Hans , Short Aidan. W. , Wee Alison. K.S. , Jajoo Anjana , Aritsara Amy Ny Aina , Kajita Tadashi , Cao Kun-Fang
Published: April 2024

Cold waves restrict the distribution of mangroves. This study examined the contribution of PSII heterogeneity and stomatal functioning to sustaining photochemistry and photoprotection in mangroves during a cold wave. We exposed eight populations of Kandelia obovata (cold-tolerant) and, Bruguiera gymnorhiza (cold-susceptible) from different latitudes to 27/20°C (favorable) and 10/3°C (chilling; simulated cold wave) day and night temperatures. Multiple trait responses imply that cold waves affected K. obovata the least. Significant changes in chlorophyll fluorescence transients (photosystem II [PSII]) with a slight decrease in the redox status of P700 (photosystem I [PSI]) imply a greater impact of a cold wave on PSII. During the cold wave, photochemical efficiency of PSII, efficiency of the water-splitting complex, light absorptance, stomatal pore area, cyclic electron flow, nonphotochemical quenching, and number of active PSIIα and PSII QB reducing centers decreased, while light transmittance, night respiration, and inactive PSII QB nonreducing, PSIIβ, and γ centers increased in both species. The population of K. obovata from the coldest latitudinal site (Fujian, China) was least affected by cold wave due to local evolutionary adaptations. Modulation of PSII heterogeneity and stomatal functioning is important to sustaining photochemistry and photoprotection in mangroves to cope with cold waves.

Highlights

PSII heterogeneity and stomatal functioning support mangroves to cope with cold waves.

Local evolutionary adaptations promote the cold tolerance of mangrove populations.
Accelerated somatic mutation calling for whole-genome and whole-exome sequencing data from heterogenous tumor samples
Authors: Ji Shuangxi , Zhu Tong , Sethia Ankit , Wang Wenyi
Published: April 2024

Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenges were overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE 2, powered by multistep parallelization and efficient memory allocation, to resolve the computing time bottleneck. MuSE 2 speeds up 50 times more than MuSE 1 and eight to 80 times more than other popular callers. Our benchmark study suggests combining MuSE 2 and the recently accelerated Strelka2 achieves high efficiency and accuracy in analyzing large cancer genomic data sets.
Breakdown insensitive acceleration regime in a metamaterial accelerating structure
Authors: Merenich Dillon , Leung Brendan , Rijal Gaurab , Lu Xueying , Doran Scott , Chen Gongxiaohui , Liu Wanming , Jing Chunguang , Power John , Whiteford Charles , Wisniewski Eric
Published: April 2024

A new regime in radiofrequency (rf) breakdown, named the breakdown insensitive acceleration regime (BIAR), was observed in an 11.7 GHz metamaterial structure for wakefield acceleration driven by rf pulses with a duration of a few nanoseconds. In the BIAR, rf breakdown occurs without interrupting potential beam acceleration, resulting in greater resilience to breakdown. We have investigated the possibility that BIAR can support higher gradients by characterizing the breakdown in a high-power test. The peak gradient reached 190  MV/m when the structure was powered by 6 ns long rf pulses with 115 MW peak power. The short rf pulses were extracted from 65 MeV electron bunch trains with a total charge of up to 210 nC. This work has revealed the benefits of short-pulse acceleration by characterizing rf breakdown in the previously unexplored parameter space.

Published by the American Physical Society
2024
Longitudinal compression of a macrorelativistic electron beam
Authors: Li An , Shi Jiaru , Zha Hao , Gao Qiang , Zhou Liuyuan , Chen Huaibi
Published: April 2024

We present a novel concept of longitudinal bunch train compression that can manipulate a relativistic electron beam across hundreds of meters. This concept holds the potential to compress the electron beam produced by a conditional linear accelerator at a high ratio, elevating its power to a level comparable with large induction accelerators. The method employs the spiral motion of electrons in a uniform magnetic field to fold hundreds-of-meters-long trajectories into a compact setup. The interval between bunches can be fine-tuned by modulating their spiral movement. We explore this method with the particle dynamic simulation. Compared to setups of similar size, such as a chicane, our method can compress bunches at considerably larger scales. Consequently, it opens up new possibilities for generating high-power beams using compact devices at lower costs.

Published by the American Physical Society
2024
Next-to-soft radiation from a different angle
Authors: van Beekveld Melissa , Danish Abhinava , Laenen Eric , Pal Sourav , Tripathi Anurag , White Chris D.
Published: April 2024

Soft and collinear radiation in collider processes can be described in a universal way, that is independent of the underlying process. Recent years have seen a number of approaches for probing whether radiation beyond the leading soft approximation can also be systematically classified. In this paper, we study a formula that captures the leading next-to-soft QCD radiation affecting processes with both final- and initial-state partons, by shifting the momenta in the nonradiative squared amplitude. We first examine W+jet production, and show that a previously derived formula of this type indeed holds in the case in which massive color singlet particles are present in the final state. Next, we develop a physical understanding of the momentum shifts, showing precisely how they disrupt the well-known angular ordering property of leading soft radiation.

Published by the American Physical Society
2024
Axionlike-particle contributions to the
μ→e
conversion
Authors: Fuyuto Kaori , Mereghetti Emanuele
Published: April 2024

We study the μ→e conversion process in nuclear targets arising in models of axionlike particles (ALPs) with hadronic and charged lepton flavor violating (CLFV) interactions. Contributions to this process generally fall into two categories: spin-independent (SI) and spin-dependent (SD). While the SI contribution can be generated by a dipole operator through purely leptonic ALP interactions, the SD contribution can also be present through ALP-quark interactions at tree-level. It is naively anticipated that the SI contribution would be dominant due to its coherent enhancement. In this paper, we show that is not generically the case; in particular, for naturally sized ALP couplings to quarks of order ∼mq/fa, the SD interaction induced by ALP-π0 mixing turns out to be the leading contribution to μ→e conversion. Intuitively, this stems from the suppressed dipole contribution by the QED one-loop factor which counters the effect of SI coherent enhancement. Our study highlights the importance of μ→e conversion searches in exploring the parameter space of generic ALP models, and demonstrates the competitiveness of these searches in probing the CLFV ALP parameter space in the heavy mass range of ma≳mμ.

Published by the American Physical Society
2024
The credibility of external audits of management systems – the audited enterprises’ perspective
Authors: Rogala Piotr , Kafel Piotr , Urbaniak Maciej
Published: April 2024

Purpose

This paper deals with external audits, which are now commonly used in many industries (e.g. food, automotive and electrical). This study aims to assess whether a given organization meets the specific criteria. If the audit ends with a positive result, information about it is provided to selected interested parties, e.g. clients or contractors. Credibility is pivotal in adding value for all interested parties within the audit processes. This study seeks the factors which, in the opinion of the audited enterprises, have the most decisive impact on the credibility of external audits.

Design/methodology/approach

In keeping with the extant literature, research questions were developed regarding the factors influencing the credibility assessment of external audits. Data collected from 100 companies in the Polish food sector were used to construct the model and carry out statistical analyses. Linear regression analyses were also applied to determine the key factors influencing the credibility of audits.

Findings

This study is part of the research trend on the rationality of external audits and certification of quality management systems. This paper identifies nine main factors shaping the credibility of external audits. Two of them have the most decisive influence on credibility. The first one is the professional audit method (procedure). The second factor is the auditor’s knowledge of the specificity of the audited area.

Research limitations/implications

This study did not consider the impact that the image/credibility of the organization represented by the auditors may have on the reliability of audits. This is one of the fundamental limitations that should be considered when analyzing the obtained results. To recognize this type of dependence, additional research should be carried out. Another limitation is that the research covers the food industry only. It would be interesting to know the situation in other types of industries.

Practical implications

This paper looks at the possibility of increasing the added value for audited enterprises. The proposed model can be used by managers of organizations conducting external audits and auditors to effectively use resources for process improvement, influencing the maximization of credibility of activities in the area of conformity assessment.

Originality/value

The originality of this study lies in adopting the perspective of audited enterprises in assessing the credibility of audits. To the best of the authors’ knowledge, this is the first study that adopts this approach. This paper contributes to the literature, particularly to better understand audited enterprises’ behavior (trust in audit results, satisfaction with audits, etc.).
Building employee commitment through internal branding – a meta-analytic study
Authors: Prashar Atul , Maity Moutusy
Published: April 2024

Purpose

This study aims to quantitatively consolidate the research conducted over the past four decades on how internal branding activities drive employee commitment. It summarizes several operationalizations of internal branding and tests the moderating effect of employee’s personal characteristics and job characteristics on the relationship between internal branding and employee commitment.

Design/methodology/approach

This paper uses meta-analysis as the research methodology. The analysis includes a sample of 65 studies (from 62 published works), yielding 226 effect sizes (coded into 82 composite effect sizes) over an aggregated sample of 21,706 respondents.

Findings

This study finds that brand communication, brand-centered human resource management (HRM), training and development, organizational support and culture, brand-centered leadership and an excellent reward system are the key operationalizations of internal branding. Furthermore, employee’s personal (education, age and gender) and job (tenure, work status and level of customer orientation) characteristics significantly moderate the internal branding–employee commitment relationship.

Research limitations/implications

Limited empirical literature on some of the internal branding operationalizations such as brand-centered HRM and rewards has curbed the scope of moderator analysis.

Practical implications

This paper proposes some effective ways of implementing internal branding strategies and provides support for boundary conditions that brand managers should consider to strengthen the impact of internal branding activities on employee commitment.

Originality/value

As per the authors’ knowledge, this paper is among the few quantitative consolidations of four decades of research on the internal branding–employee commitment relationship.
Business scholars’ time allocation under the lens of the self-managed approach of academic’s role and the outcome-focused perspective of university’s strategic management
Authors: Amara Nabil , Rhaiem Mehdi
Published: April 2024

Purpose

This article explores whether six broad categories of activities undertaken by Canadian business scholars’ academics: publications record, citations record, teaching load, administrative load, consulting activities, and knowledge spillovers transfer, are complementary, substitute, or independent, as well as the conditions under which complementarities, substitution and independence among these activities are likely to occur.

Design/methodology/approach

A multivariate probit model is estimated to take into account that business scholars have to consider simultaneously whether or not to undertake many different academic activities. Metrics from Google Scholar of scholars from 35 Canadian business schools, augmented by a survey data on factors explaining the productivity and impact performances of these faculty members, are used to explain the heterogeneities between the determinants of these activities.

Findings

Overall, the results reveal that there are complementarities between publications and citations, publications and knowledge spillovers transfer, citations and consulting, and between consulting and knowledge spillovers transfer. The results also suggest that there are substitution effects between publications and teaching, publications and administrative load, citations and teaching load, and teaching load and administrative load. Moreover, results show that public and private funding, business schools’ reputation, scholar’s relational resources, and business school size are among the most influential variables on the scholar’s portfolio of activities.

Originality/value

This study considers simultaneously the scholar’s whole portfolio of activities. Moreover, the determinants considered in this study to explain scholars’ engagement in different activities reconcile two conflicting perspectives: (1) the traditional self-managed approach of academics, and (2) the outcomes-focused approach of university management.
Accessing vicarious nostalgia and memorable tourism experiences in the context of heritage tourism with the moderating influence of social return
Authors: Bhogal Sachin , Mittal Amit , Tandon Urvashi
Published: April 2024

Purpose

Heritage tourism is an increasingly popular form of tourism that allows individuals to connect with the past and immerse themselves in cultural and historical narratives. Hence, the purpose of this study is to explore the intricate relationships among vicarious nostalgia (VNOS), memorable tourism experiences (MTEXs) and their collective influence on tourists’ behavioral intentions (BINTs). Additionally, this study examines the moderating effect of social return (SN) in the context of heritage tourism.

Design/methodology/approach

Data were gathered using a self-administered questionnaire from 259 tourists visiting heritage sites in Jaipur. The proposed model was tested using structural equation modeling.

Findings

The results confirmed that VNOS had a significant positive impact on BINT in the context of heritage tourism. The causal relationship between VNOS and BINT was fully mediated by MTEX. The results further verified that the presence of SN strengthens the association between MTEXs and BINT.

Practical implications

This research will guide the firms associated with heritage tourism to target specific cohorts interested in heritage tourism. Policymakers may find it easier to create unique offerings and packages that appeal to visitors interested in historical sites and produce memorable travel experiences. One key implication is to create “social media friendly spaces” at different locations of the sites. To increase tourism, managers may use the findings from this research to create plans for the ethical promotion and protection of cultural and natural heritage sites.

Originality/value

Overall, this research advances the understanding of the role of VNOS in heritage tourism by elucidating its cognitive and emotional aspects and their subsequent influence on the memorability of tourist experiences and BINT s. Additionally, by considering the moderating effect of SN, this study provides a comprehensive view of how these factors collectively shape tourists’ decisions and actions in the context of heritage destinations. This research has been conducted in the heritage city of Jaipur (North-Western India), which, surprisingly – despite its popularity as a heritage tourism site – has not been sufficiently explored in the scholarly research.
Nomination and remuneration committee: a review of literature
Authors: Putra Ferdy , Setiawan Doddy
Published: April 2024

Purpose

This paper aims to synthesize the diverse literature on nomination and remuneration committees and provide avenues for future research.

Design/methodology/approach

This study provides a comprehensive literature review of theoretical and empirical studies published in reputable international journals indexed by Scopus.

Findings

The literature review reveals several aspects of the nomination and remuneration committee. These aspects have been classified into the definition of the nomination and remuneration committee, dimensions of the nomination and remuneration committee, measurement and research review results, reasons for conflict empirical findings, company dynamics and research on moderators, as well as recommending future research.

Research limitations/implications

Our literature review shows that nomination and remuneration committees play a role in improving board performance and company performance, reducing agency conflicts and improving corporate governance to provide implications for companies, regulators and investors and pave the way for future research.

Originality/value

This paper identifies issues related to nomination and remuneration committees, their theoretical and practical implications and avenues for future research.