bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease-associated gut microbiome and metabolome changes in chronic low back pain patients with bone marrow lesions
Authors: Li Wentian , Tu Ji , Zheng Jinjian , Das Abhirup , Yan Qi , Jiang Xiaotao , Ding Wenyuan , Bai Xupeng , Lai Kaitao , Yang Sidong , Yang Cao , Zou Jun , Diwan Ashish D , Zheng Zhaomin 
Published: July 2023

AbstractChronic low back pain (LBP) is the leading cause of global disability. Vertebral bone marrow lesions (BMLs), one etiological factor for chronic LBP, are MRI signal changes in the vertebral bone marrow that extend from the disc endplate. The adipogenesis of bone marrow mesenchymal stem cells (BM-MSCs) could explain fatty replacement (FR) in normal bone marrow. FR is the most common type of BMLs. Here we show how the gut microbiome and serum metabolome change and how they interact in LBP patients with or without FR. The serum metabolome of chronic LBP patients with FR is characterized by decreased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has important capability to regulate BCAA degradation pathway.Ruminococcus gnavus, Roseburia hominis and Lachnospiraceae bacterium 8 1 57FAAare identified as the main species driving the association between biosynthesis of BCAAs and BM-MSCs metabolism in LBP with FR individuals.In vitrowork demonstrates that BCAAs can induce the adipogenesis of BM-MSCs by activating the SIRT4 pathway. Our findings provide a deep insight into understanding the role of the disturbed gut ecosystem in FR and LBP.
The transcriptome landscape of developing barley seeds reveals H3K27me3 dynamics in endosperm tissues
Authors: Kovacik Martin , Nowicka Anna , Zwyrtková Jana , Strejčková Beáta , Vardanega Isaia , Esteban Eddi , Pasha Asher , Kaduchová Kateřina , Krautsova Maryna , Šafář Jan , Provart Nicholas J. , Simon Rüdiger , Pecinka Ales 
Published: July 2023

AbstractCereal grains are an important food and feed. To provide comprehensive spatiotemporal information about biological processes in developing seeds of cultivated barley, we performed a transcriptomic study of the embryo, endosperm, and seed maternal tissues collected from 4 to 32 days after pollination. Weighted gene co-expression network and motif enrichment analyses pointed out specific groups of genes and transcription factors with possible impacts on regulating barley seed tissue development. We defined a set of tissue-specific marker genes and families of transcription factors for functional studies of the pathways controlling barley grain development. Assessment of selected groups of chromatin regulators revealed that epigenetic processes are highly dynamic and likely to play a major role during barley endosperm development. Repressive modification H3K27me3 is globally reduced in endosperm tissues and at specific developmental and storage compound genes. Altogether, this atlas uncovers the complexity of the developmental regulation of gene expression in barley grains.TeaserSpatiotemporal profiling of developing barley seeds revealed loss of H3K27me3 and changes in gene expression in endosperm.
The transcriptional response in mosquitoes distinguishes between fungi and bacteria but not Gram types
Authors: Hixson Bretta , Huot Louise , Morejon Bianca , Yang Xiaowei , Nagy Peter , Michel Kristin , Buchon Nicolas 
Published: July 2023

AbstractMosquitoes are prolific vectors of human pathogens; a clear and accurate understanding of the organization of their antimicrobial defenses is crucial for informing the development of transmission control strategies. The canonical infection response in insects, as described in the insect modelDrosophila melanogaster, is pathogen type-dependent, with distinct stereotypical responses to Gram-negative bacteria and Gram-positive bacteria/fungi mediated by the activation of the Imd and Toll pathways, respectively. To determine whether this pathogen-specific discrimination is shared by mosquitoes, we used RNAseq to capture the genome-wide transcriptional response ofAedes aegyptiandAnopheles gambiae(s.l.) to systemic infection with Gram-negative bacteria, Gram-positive bacteria, yeasts, and filamentous fungi, as well as challenge with heat-killed Gram-negative, Gram-positive, and fungal pathogens. From the resulting data, we found thatAe. aegyptiandAn. gambiaeboth mount a core response to all categories of infection, and this response is highly conserved between the two species with respect to both function and orthology. When we compared the transcriptomes of mosquitoes infected with different types of bacteria, we observed that the intensity of the transcriptional response was correlated with both the virulence and growth rate of the infecting pathogen. Exhaustive comparisons of the transcriptomes of Gram-negative-challenged versus Gram-positive-challenged mosquitoes yielded no difference in either species. InAe. aegypti, however, we identified transcriptional signatures specific to bacterial infection and to fungal infection. The bacterial infection response was dominated by the expression of defensins and cecropins, while the fungal infection response included the disproportionate upregulation of an uncharacterized family of glycine-rich proteins. These signatures were also observed inAe. aegyptichallenged with heat-killed bacteria and fungi, indicating that this species can discriminate between molecular patterns that are specific to bacteria and to fungi.
BRD4 isoforms have distinct roles in tumor progression and metastasis in embryonal rhabdomyosarcoma
Authors: Das Dipanwita , Leung Jia Yu , Tergaonkar Vinay , Loh Amos Hong Pheng , Chiang Cheng-Ming , Taneja Reshma 
Published: July 2023

ABSTRACTBRD4, a bromodomain and extraterminal (BET) protein, is deregulated in multiple cancers and has emerged as a promising drug target. However, the function of the two main BRD4 isoforms (BRD4-L and BRD4-S) has not been analyzed in parallel in most cancers. This complicates determining therapeutic efficacy of pan-BET inhibitors. In this study, using functional and transcriptomic analysis, we show that BRD-L and BRD4-S isoforms play distinct roles in embryonal rhabdomyosarcoma. BRD4-L has an oncogenic role and inhibits myogenic differentiation, at least in part, by activating myostatin expression. Depletion of BRD4-Lin vivoimpairs tumor progression but does not impact metastasis. On the other hand, depletion of BRD4-S has no significant impact on tumor growth, but strikingly promotes metastasisin vivo. Interestingly, BRD4-S loss results in the enrichment of BRD4-L and RNA Polymerase II at integrin gene promoters resulting in their activation. Our work unveils isoform-specific functions of BRD4 and demonstrates that BRD4-S functions as a gatekeeper to constrain the full oncogenic potential of BRD4-L.
Asymmetric cell division-specific phosphorylation of PAR-3 regulates neuroblasts polarisation and sensory organ formation inDrosophila
Authors: Loyer Nicolas , Hogg Elizabeth K. J. , Shaw Hayley , Murray David H. , Findlay Greg M. , Januschke Jens 
Published: July 2023

AbstractThe generation of distinct cell fates during development depends on asymmetric cell division of progenitor cells. In the central and peripheral nervous system ofDrosophila,progenitor cells respectively called neuroblasts or sensory organ precursors use PAR polarity during mitosis to control cell fate determination in their daughter cells. How polarity and the cell cycle are coupled, and how the cell cycle machinery regulates PAR protein function and cell fate determination is poorly understood. Here, we generate an analog sensitive allele of CDK1 and reveal that its partial inhibition weakens but does not abolish apical polarity in embryonic and larval neuroblasts, and leads to defects in polarisation of fate determinants. We describe a novelin vivophosphorylation of Bazooka, theDrosophilahomolog of PAR-3, on Serine180, a consensus CDK phosphorylation site. Remarkably, phosphorylation of Serine180 occurs in asymmetrically dividing neuroblasts and sensory organ precursors, and not in their symmetrically dividing neighbours. We further show that Serine180 phosphomutants disrupt the timing of basal polarisation in neuroblasts and sensory organ formation in sensory organ precursors. Finally, we show that CDK1 can phosphorylate human PARD3in vitro,suggestive of a conserved kinase-substrate relationship between CDK1 and PAR-3.
Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern
Authors: Chen Qi , Qin Si , Zhou Hang-Yu , Deng Yong-Qiang , Shi Pan-Deng , Zhao Hui , Li Xiao-Feng , Huang Xing-Yao , Wu Ya-Rong , Guo Yan , Pei Guang-Qian , Wang Yun-Fei , Sun Si-Qi , Du Zong-Min , Cui Yu-Jun , Fan Hang , Qin Cheng-Feng 
Published: July 2023

AbstractSARS-CoV-2 variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22995 and 28866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.ImportanceSARS-CoV-2 variants or subvariants keep emerging and the epidemic strains keeps changing in humans and animals. The continued replacement of the epidemic strains was attributed to higher competitive fitness evolved by the newly appeared ones than the older ones, but which factors affect the final outcomes are still not entirely clear. In this study, we performed in vitro coinfection and serial passage with three VOCs and WT under different conditions. Our results showed that the competition outcomes of these viral strains varied in different cell lines or under different immune pressure, confirming the probable effects of these two factors for the competitive fitness of different SARS-CoV-2 viral strains. Meanwhile, strikingly, we found that coinfection and serial passage with different SARS-CoV-2 viral strains can mimic the recombination process of SARS-CoV-2 occurred in coinfection individual, indicating it is a novel model to investigate the SARS-CoV-2 recombination mechanism.
Together Inbreeding and Reproductive Compensation Favor Lethalt-Haplotypes
Authors: Munasinghe Manisha , Brandvain Yaniv 
Published: July 2023

AbstractMale mice who are heterozygous for distorting and non-distorting alleles at thet-haplotype transmit the drivingt-haplotype around 90% of the time – a drastic departure from Mendelian expectations. This selfish act comes at a cost. The mechanism underlying transmission distortion in this system causes severe sterility in males homozygous for the drive alleles, ultimately preventing its fixation. Curiously, many drivingt-haplotypes also induce embryonic lethality in both sexes when homozygous, however, this is neither universal nor a necessity for this distortion mechanism. Charlesworth provided an adaptive explanation for the evolution of lethalt-haplotypes in a population segregating for distorting and non-distortingtalleles – namely, if mothers compensate by replacing dead embryos with new offspring (or by transferring energy to surviving offspring), a recessive lethal can be favored because it effectively allows mothers the opportunity to trade in infertile males for potentially fertile offspring. However, this model requires near complete reproductive compensation for the invasion of the lethalt-haplotype and produces an equilibrium frequency of lethal drivers well below what is observed in nature. We show that even low levels of systemic inbreeding, which we model as brother-sister mating, allows lethalt-haplotypes to invade with much lower levels of reproductive compensation. Furthermore, inbreeding allows these lethal haplotypes to largely displace the ancestral male-sterile haplotypes. Our results show that together inbreeding and reproductive compensation move expected equilibria closer to observed haplotype frequencies in natural populations and occur under more reasonable parameter combinations.
Raf1 promotes successful Human Cytomegalovirus replication and is regulated by AMPK-mediated phosphorylation during infection
Authors: Dunn Diana M. , Pack Ludia J. , Munger Joshua C. 
Published: July 2023

AbstractRaf1 is a key player in growth factor receptor signaling, which has been linked to multiple viral infections, including Human Cytomegalovirus (HCMV) infection. Although HCMV remains latent in most individuals, it can cause acute infection in immunocompromised populations such as transplant recipients, neonates, and cancer patients. Current treatments are suboptimal, highlighting the need for novel treatments. Multiple points in the growth factor signaling pathway are important for HCMV infection, but the relationship between HCMV and Raf1, a component of the mitogen-activated protein kinase (MAPK) cascade, is not well understood. The AMP-activated protein kinase (AMPK) is a known regulator of Raf1, and AMPK activity is both induced by infection and important for HCMV replication. Our data indicate that HCMV infection induces AMPK-specific changes in Raf1 phosphorylation, including increasing phosphorylation at Raf1-Ser621, a known AMPK phospho-site, which results in increased binding to the 14-3-3 scaffolding protein, an important aspect of Raf1 activation. Inhibition of Raf1, either pharmacologically or via shRNA or CRISPR-mediated targeting, inhibits viral replication and spread in both fibroblasts and epithelial cells. Collectively, our data indicate that HCMV infection and AMPK activation modulate Raf1 activity, which are important for viral replication.ImportanceGrowth factor signaling plays a critical role in many aspects of viral infection. Here we show that a component of one of these pathways, Raf1, contributes to successful infection of Human Cytomegalovirus (HCMV). We find that AMP-activated protein kinase (AMPK), which is known to be important for HCMV infection, modulates Raf1 phosphorylation throughout infection, and contributes to Raf1 binding to its activating co-factor, 14-3-3. In addition, inhibition of Raf1 inhibits HCMV infection and viral spread. These results suggest a link between two cellular pathways that are important for HCMV replication, AMPK signaling and growth factor receptor signaling, that converge as an important aspect of HCMV infection. This could lead to the potential for new therapeutic targets in immunocompromised individuals afflicted by acute HCMV infection.
Metabolic impact of heterologous protein production inPseudomonas putida: Insights into carbon and energy flux control
Authors: Vogeleer Philippe , Millard Pierre , Ortega Arbulú Ana-Sofia , Pflüger-Grau Katharina , Kremling Andreas , Létisse Fabien 
Published: July 2023

AbstractFor engineered microorganisms, the production of heterologous proteins that are often useless to host cells represents a burden on resources, which have to be shared with normal cellular processes. Within a certain metabolic leeway, this competitive process has no impact on growth. However, once this leeway, or free capacity, is fully utilized, the extra load becomes a metabolic burden that inhibits cellular processes and triggers a broad cellular response, reducing cell growth and often hindering the production of heterologous proteins. In this study, we sought to characterize the metabolic rearrangements occurring in the central metabolism ofPseudomonas putidaat different levels of metabolic load. To this end, we constructed aP. putidaKT2440 strain that expressed two genes encoding fluorescent proteins, one in the genome under constitutive expression to monitor the free capacity, and the other on an inducible plasmid to probe heterologous protein production. We found that metabolic fluxes are considerably reshuffled, especially at the level of periplasmic pathways, as soon as the metabolic load exceeds the free capacity. Heterologous protein production leads to the decoupling of anabolism and catabolism, resulting in large excess energy production relative to the requirements of protein biosynthesis. Finally, heterologous protein production was found to exert a stronger control on carbon fluxes than on energy fluxes, indicating that the flexible nature ofP. putida’s central metabolic network is solicited to sustain energy production.HighlightsHeterologous protein production inP. putidareshuffles the periplasmic metabolism.Increased protein production progressively decouples catabolism from anabolism.Protein production exerts a stronger control on energy than on carbon fluxes.Glucose is directed towards ATP production to meet the elevated energy demands.
The impact of oil price and COVID-19 pandemic on clean energy stocks: an empirical approach using ARDL
Authors: Naser Hanan , Al-aali Fatima , Abdulla Yomna , Ebrahim Rabab 
Published: July 2023

PurposeOver the last decade, investments in green energy companies have witnessed noticeable growth rates. However, the glacial pace of the world economic restoration due to COVID-19 pandemic placed a high degree of uncertainty over this market. Therefore, this study investigates the short- and long-term relationships between COVID-19 new cases and WilderHill New Energy Global Innovation Index (NEX) using daily data over the period from January 23, 2020 to February 1, 2023.Design/methodology/approachThe authors utilize an autoregressive distributed lag bounds testing estimation technique.FindingsThe results show a significant positive impact of COVID-19 new cases on the returns of NEX index in the short run, whereas it has a significant negative impact in the long run. It is also found that the S&P Global Clean Energy Index has a significant positive impact on the returns of NEX index. Although oil has an influential effect on stock returns, the results show insignificant impact.Practical implicationsGovernments have the chance to flip this trend by including investment in green energy in their economic growth stimulation policies. Governments should highlight the fundamental advantages of investing in this type of energy such as creating job vacancies while reducing emissions and promoting innovation.Originality/valueFirst, as far as the authors are aware, the authors are the first to examine the effect of oil prices on clean energy stocks during COVID-19. Second, the authors contribute to studies on the relationship between oil prices and renewable energy. Third, the authors add to the emerging strand of literature on the impact of COVID-19 on various sectors of the economy. Fourth, the findings of the paper can add to the growing literature on sustainable development goals, in specific the papers related to energy sustainability.
Natural convection in a differentially heated cavity filled with a Brinkman bidisperse porous medium
Authors: Grosan Teodor , Patrulescu Flavius-Olimpiu , Pop Ioan 
Published: July 2023

Purpose
The purpose of this work is the study of the steady free convection in a square differentially heated cavity filled by a Brinkman bidisperse porous medium. An appropriate mathematical model considering the Brinkman, momentum and energy interphase terms is proposed. The dependence of the stream functions, isotherms and of the Nusselt numbers on the governing parameters is analysed.

Design/methodology/approach
The both phases of flow and heat transfer are solved numerically using a modified finite difference technique. The algebraic system obtained after discretization is solved using the SOR method. The results are found to be in a significant agreement with the ones presented by the literature for a Darcy bidisperse porous medium and a Brinkman monodisperse porous medium.

Findings
The effects of the governing parameters on stream functions, isotherms and Nusselt numbers are discussed. It has been found that in the case of the Brinkman bidisperse model, the Nusselt numbers decrease compared to the Darcy model, and this behaviour is significant in comparison to the Brinkman monodisperse case.

Originality/value
A mathematical model for the free convection inside a cavity filled by a non-Darcy bidisperse porous medium, based on the Brinkman equation, is used. The effect of Darcy number, Rayleigh number, modified inter-phase heat transfer parameter, modified thermal conductivity ratio and the inertial parameters is studied. To the best of the authors’ knowledge, this problem has not been studied before, and the results are new and original.
Dynamics of user-generated content and service failure recovery: evidence from millennials
Authors: Ozuem Wilson , Willis Michelle , Ranfagni Silvia , Howell Kerry , Rovai Serena 
Published: July 2023

Purpose
There is considerable interest in the value of user-generated content (UGC) and its antecedents. Despite its growing importance, existing studies have largely ignored the effects of UGC on customers’ responses to recovery efforts in the fashion industry. The aim of this paper is to examine the extent to which UGC influences customers’ responses to providers’ service failure and recovery efforts, particularly how millennials’ interactions impact recovery efforts.

Design/methodology/approach
The study uses a phenomenological hermeneutics and adopts theoretical sampling to collect empirical data from three European countries (France, Italy and the UK). The authors interviewed 60 millennials who had online service failure experiences in online fashion. This methodological framework was designed to illustrate the close relationships between subject and object as well as identify that data analysis and collection are undertaken in relation to consistent iterative interpretations in an evolving process of study. Drawing on multi-theoretical lenses, using actor–network and social influence theories, this study advances understanding through the development of a new conceptual model relating to individual characteristics.

Findings
Using actor–network theory and social influence theory, this study developed a conceptual model of four customer groups’ responses to service failure based on the severity of service failure and the level of customers’ online response following service failure.

Originality/value
The authors suggest some pragmatic implications of their conceptual model and explain how awareness of different customer groups can lead to effective decision-making for marketers. This study provides a set of practical insights that brand managers can use to recover service failures.