bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of heat-stressed transcriptomes using the public gene expression database from human and mouse samples
Authors: Yonezawa Sora , Bono Hidemasa 
Published: May 2023

AbstractBackgroundClimate change has significantly increased the frequency of exposure to heat, adversely affecting human health and various industrial sectors. Heat stress is an environmental stress defined as the exposure of organisms and cells to abnormally high temperatures. Heat-stress research has predominantly focused on response systems involving heat shock factors acting as transcription factors and heat shock proteins functioning as molecular chaperones. However, to comprehensively elucidate the mechanisms underlying an organism’s response to heat stress, it is essential to investigate and analyze genes that have been underrepresented, less well-known, or overlooked in previous studies. In this study, we analyzed heat stress-responsive genes using a meta-analysis of numerous gene expression datasets.ResultsFirst, we collected paired heat exposure and control data from public databases. Gene expression data were obtained for 322 human and 242 mouse pairs. The expression ratios (HN-ratios) of the collected pairs were calculated, and the identification of upregulated and downregulated expression profiles was determined according to defined thresholds. The number of upregulated and downregulated genes was calculated as the heat stress - non-treatment score (HN-score), which is the value of: [number of upregulated genes] - [number of downregulated genes] for each gene and was used as the index of analysis. The HN-score comprehensively evaluated gene expression variation, and 76 upregulated and 37 downregulated genes common to human and mouse were identified. We performed enrichment, protein-protein interaction network, and transcription factor target gene analyses. Furthermore, we evaluated the extracted genes through integrated analysis using publicly available ChIP-seq data for HSF1, HSF2, and PPARGC1A (PGC1-α), and gene2pubmed data, which were sourced from previous literature. The results identified previously overlooked genes, such asABHD3,ZFAND2A, andUSPL1, as commonly upregulated genes.ConclusionsBased on the findings of this study, further functional analysis of the extracted genes using genome editing and other technologies has the potential to contribute to coping with climate change and potentially lead to new knowledge and technological advances.
Ketone-loading as A Novel Sports Nutrition Strategy: Chronic Ketone Supplementation Elicits Further Favorable Metabolic Changes in Keto-adapted Mice
Authors: Ma Sihui , Onogi Shiori , Jia Huijuan , Kato Hisanori , Suzuki Katsuhiko 
Published: May 2023

AbstractBackgroundA ketogenic diet (KD) induces nutritional ketosis (NS), benefits fatty acid oxidation (FAO), and favors moderate-intensity exercise capacity. The status that the body accommodates to produce and utilize ketone bodies (KB) and fatty acids as primary fuel sources is termed keto-adaptation. However, keto-adaptation requires time, while long-term KD also involves unfavored adverse effects. Exogenous ketone body (EKBs) administration has been introduced to elicit the advantages of NS. However, the direct use of EKBs fails to bring desired outcomes. We hypothesized that EKBs might only be effective during keto-adaptation.MethodsMale C57BL/6J mice (n = 24) were divided into three groups: a control diet (Con, n = 8), a ketogenic diet (KD, n = 8), and a KD plus a ketone body (DL-β-Hydroxybutyric acid sodium salt, BHB) administration (KD+BHB, n = 8). After six weeks of KD administration, mice in the KD+BHB group receive BHB added into water bottles for another six weeks. Blood KB concentration is monitored throughout the experiment, while liver, gastrocnemius, and soleus mRNA are analyzed using RT-PCR.ResultsBoth KD and KD+BHB induced and sustained NS and enhanced hepatic and muscular key genes regulating FAO. In addition, BHB administration upon keto-adaptation further increased circulating KB concentration and enhanced expressional levels of FAO-mediating genes (ACO, HADH, ACADM, andMLYCDin the gastrocnemius muscle;ACO, HADH, andMLYCDin the soleus muscle), and energy-regulating genes (PPARAandPPARG) in the liver and skeletal muscle compared to a KD.ConclusionCompared to KD alone, chronic administration of KBs upon keto-adaptation increased the expression of key genes that favor FAO or maintain energy homeostasis in the liver and skeletal muscle. Instead of directly using EKBs in non-keto-adapted individuals, it is encouraged to use EKBs upon keto-adaptation status to elicit their energy-utilizing effects.HighlightsThis is the first report to evaluate the metabolic effects using exogenous ketone bodies on keto-adapted individuals.Administration of exogenous ketone body upon keto-adaptation furtherly increased circulating ketone bodies.Administration of exogenous ketone body upon keto-adaptation individuals enhanced expression of genes related to fatty acid oxidation and energy hemostasis.
Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease
Authors: Fowler S. L. , Behr T. S. , Turkes E. , Cauhy P. Maglio , Foiani M. S. , Schaler A. , Crowley G. , Bez S. , Ficulle E. , Tsefou E. , O’Brien D. P. , Fischer R. , Geary B. , Gaur P. , Miller C. , D’Acunzo P. , Levy E. , Duff K. E. , Ryskeldi-Falcon B. 
Published: May 2023

SUMMARYThe abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.
The LRRK2 kinase substrates Rab8a and Rab10 contribute complementary but distinct disease-relevant phenotypes in human neurons
Authors: Mamais Adamantios , Sanyal Anwesha , Fajfer Austin , Zykoski Catherine G. , Guldin Michael , Riley-DiPaolo Alexis , Subrahmanian Nitya , Gibbs Whitney , Lin Steven , LaVoie Matthew J. 
Published: May 2023

AbstractMutations in the LRRK2 gene cause familial Parkinson’s disease presenting with pleomorphic neuropathology that can involve α-synuclein or tau accumulation. LRRK2 mutations are thought to converge toward a pathogenic increase in LRRK2 kinase activity. A subset of small Rab GTPases have been identified as LRRK2 substrates, with LRRK2-dependent phosphorylation resulting in Rab inactivation. We used CRISPR/Cas9 genome editing to generate a novel series of isogenic iPSC lines deficient in the two most well validated LRRK2 substrates, Rab8a and Rab10, from two independent, deeply phenotyped healthy control lines. Thorough characterization of NGN2-induced neurons revealed divergent effects of Rab8a and Rab10 deficiency on lysosomal pH, LAMP1 association with Golgi, α-synuclein insolubility and tau phosphorylation, while parallel effects on lysosomal numbers and Golgi clustering were observed. Our data demonstrate largely antagonistic effects of genetic Rab8a or Rab10 inactivation which provide discrete insight into the pathologic features of their biochemical inactivation by pathogenic LRRK2 mutation.HighlightsRab8a and Rab10 deficiency induce lysosomal and Golgi defectsRab8a and Rab10 deficiency induce opposing effects on lysosomal pHRab8a KO and Rab10 KO neurons show divergent effects on synuclein and tau proteostasisInactivation of different Rab GTPases can induce distinct disease-relevant phenotypes
To call or not to call: Persistence of flexible alternative reproductive tactics in a tree cricket
Authors: Sadiq Mohammed Aamir , Torsekar Viraj R. , Balakrishnan Rohini 
Published: May 2023

AbstractAlternative reproductive tactics (ARTs) are discrete polymorphisms that help maximise reproductive success. Although flexible ARTs are ubiquitous, theoretical predictions for why flexible ARTs persist over evolutionary time have rarely been empirically tested. We hypothesised that flexible ARTs will persist if they have equal fitness benefits under a range of ecological contexts, or, there are trade-offs between ARTs in different ecological contexts and individuals display the most optimal phenotype in a context-dependent manner. Specifically, we investigated predation risk effects on the expression and fitness consequences of two flexible ARTs: acoustic signalling and being silent, expressed by tree cricketOecanthus henryimales. In large outdoor enclosures, we exposed natural populations ofO. henryito three different abundances of their predator, the green lynx spiderPeucetia viridans. Behavioural observations across successive nights revealed that higher predation risk did not alter the expression levels of the male ARTs, despite crickets experiencing differential risk and survival across treatments. Male crickets demonstrated an equal likelihood of calling or remaining silent on a night. ARTs resulted in similar mating success across differential predation risk, supporting the hypothesis that equal fitness benefits of flexible ARTs under a range of ecological contexts explain their persistence.
Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Authors: Furey Colleen , Ye Naiqing , Kercher Lisa , DeBeauchamp Jennifer , Crumpton Jeri Carol , Jeevan Trushar , Patton Christopher , Franks John , Alameh Mohamad-Gabriel , Fan Steven H.Y. , Phan Anthony T. , Hunter Christopher A. , Webby Richard J. , Weissman Drew , Hensley Scott E. 
Published: May 2023

AbstractHighly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. We generated an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. We show that the vaccine is immunogenic in mice and ferrets and prevents morbidity and mortality of ferrets following 2.3.4.4b H5N1 challenge.
Identification of a core transcriptional program driving the human renal mesenchymal-to-epithelial transition
Authors: Ng-Blichfeldt John-Poul , Stewart Benjamin J. , Clatworthy Menna R. , Williams Julie M. , Röper Katja 
Published: May 2023

SummaryDuring kidney development, nephron epithelia arisede novofrom fate-committed mesenchymal progenitors through a mesenchymal-to-epithelial transition (MET). Downstream of fate specification, transcriptional mechanisms that drive establishment of epithelial morphology through MET are poorly understood. We used human renal organoids derived from induced pluripotent stem cells, which recapitulate nephrogenesis, to investigate mechanisms controlling the renal MET programme. Multi-ome profiling of organoids revealed dynamic changes in gene expression and chromatin accessibility driven by transcriptional activators and repressors throughout renal MET. CRISPR-interference-based gene perturbation revealed that PAX8 is essential for initiation of MET in human renal organoids, contrary to mouse, by activating a cell adhesion programme. Furthermore, while Wnt/β-Catenin signalling specifies nephron fate, we find that it must be attenuated to allow HNF1B and TEAD transcription factors to drive completion of MET. These results reveal how the developing kidney balances fate-commitment and morphogenesis with implications for understanding both developmental kidney diseases and aberrant epithelial plasticity following adult renal tubular injury.
EngineeringY. lipolyticafor the biosynthesis of geraniol
Authors: Agrawal Ayushi , Yang Zhiliang , Blenner Mark 
Published: May 2023

AbstractGeraniol is a monoterpene with wide applications in the food, cosmetics, and pharmaceutical industries. Microbial production has largely used model organisms lacking favorable properties for monoterpene production. In this work, we produced geraniol in metabolically engineeredYarrowia lipolytica. First, two plant-derived geraniol synthases (GES) fromCatharanthus roseus(Cr) andValeriana officinalis(Vo) were tested based on previous reports of activity. Both wild type and truncated mutants of GES (without signal peptide targeting chloroplast) were examined by co-expressing with MVA pathway enzymes tHMG1 and IDI1. Truncated CrGES (tCrGES) produced the most geraniol and thus was used for further experimentation. The initial strain was obtained by overexpression of the truncated HMG1, IDI and tCrGES. The acetyl-CoA precursor pool was enhanced by overexpressing mevalonate pathway genes such as ERG10, HMGS or MVK, PMK. The final strain overexpressing 3 copies of tCrGES and single copies of ERG10, HMGS, tHMG1, IDI produced approximately 1 g/L in shake-flask fermentation. This is the first demonstration of geraniol production inYarrowia lipolyticaand the highest de novo titer reported to date in yeast.
Molecular crowding facilitates ribozyme-catalyzed RNA assembly
Authors: DasGupta Saurja , Zhang Stephanie , Szostak Jack W. 
Published: May 2023

ABSTRACTCatalytic RNAs or ribozymes are considered to be central to primordial biology. Most ribozymes require moderate to high concentrations of divalent cations such as Mg2+to fold into their catalytically competent structures and perform catalysis. However, undesirable effects of Mg2+such as hydrolysis of reactive RNA building blocks and degradation of RNA structures are likely to undermine its beneficial roles in ribozyme catalysis. Further, prebiotic cell-like compartments bounded by fatty acid membranes are destabilized in the presence of Mg2+, making ribozyme function inside prebiotically relevant protocells a significant challenge. Therefore, we sought to identify conditions that would enable ribozymes to retain activity in low concentrations of Mg2+. Inspired by the ability of ribozymes to function inside crowded cellular environments with <1 mM free Mg2+, we tested molecular crowding as a potential mechanism to lower the Mg2+concentration required for ribozyme-catalyzed RNA assembly. Here, we show that the ribozyme-catalyzed ligation of phosphorimidazolide RNA substrates is significantly enhanced in the presence of the artificial crowding agent polyethylene glycol. We also found that molecular crowding preserves ligase activity under denaturing conditions such as alkaline pH and the presence of urea. We also show that crowding-induced stimulation of RNA-catalyzed RNA assembly is not limited to phosphorimidazolide ligation but extends to the RNA-catalyzed polymerization of nucleoside triphosphates. RNA-catalyzed RNA ligation is also stimulated by the presence of prebiotically relevant small molecules such as ethylene glycol, ribose, and amino acids, consistent with a role for molecular crowding in primordial ribozyme function and more generally, in the emergence of RNA-based cellular life.Table of Contents GraphicSYNOPSISMolecular crowding enables ribozyme-catalyzed RNA assembly under low Mg2+conditions, and consequently may have played an essential role in the origin and evolution of RNA-based primordial life.
Importance of wildlife in the circulation and maintenance of SAT1 and SAT2 foot-and-mouth disease viruses in Africa
Authors: Duchatel Florian , Maree Francois , van Schalkwyk Louis , MdeC Bronsvoort Barend , Lycett Samantha 
Published: May 2023

AbstractAuthor summaryFoot and mouth disease (FMD) viruses are endemic in sub-Saharan Africa. Due to the complexity of the disease epidemiology and the lack of available data, there is a need to use phylogenetic approaches to understand the role of potential hosts involved in the circulation and maintenance of the viruses. The uneven host sampling of the available sequences requires us to take advantage of the recent advances in phylogenetic reconstruction. Therefore, using two structural coalescent model approximations we estimated the circulation of FMD virus serotypes SAT1 and SAT2 between cattle, buffalo and impala populations. Our results suggest that in Africa, the impala population seems to act as an intermediate host between the cattle and buffalo populations and play a more important role in the circulation of the viruses than was previously suspected. Until now, the role of the impala population in the circulation of FMDV has been suggested, but never explicitly shown.
A novel plasmid-based experimental system inSaccharomyces cerevisiaethat enables the introduction of 10 different plasmids into cells
Authors: Dong Geyao , Nakai Tsuyoshi , Matsuzaki Tetsuo 
Published: May 2023

AbstractThe budding yeastSaccharomyces cerevisiaeis commonly used as an expression platform to produce valuable compounds. Yeast-based genetics research can uniquely utilize use auxotrophy in transformant selection: auxotrophic complementation by an auxotrophic marker gene on exogenous DNA (such as plasmids). However, the number of auxotrophic nutrients required restricts the number of plasmids maintained by the cells. We therefore developed novel Δ10 strains that are auxotrophic for 10 different nutrients, and new plasmids with two multicloning sites and auxotrophic markers for use in Δ10 strains. We confirmed that Δ10 strains could maintain 10 types of these plasmids. Because each plasmid can express two different genes, this Δ10 strain-based expression system has the potential to co-express a maximum of 20 different proteins.
A Conceptual Framework for Host-Associated Microbiomes of Hybrid Organisms
Authors: Camper Benjamin T. , Laughlin Zachary , Malagon Daniel , Denton Robert , Bewick Sharon 
Published: May 2023

AbstractHybridization between organisms from evolutionarily distinct lineages can have profound consequences on organism ecology, with cascading effects on fitness and evolution. Most studies of hybrid organisms have focused on organismal traits, for example various aspects of morphology and physiology. However, with the recent emergence of holobiont theory, there has been growing interest in understanding how hybridization impacts and is impacted by host-associated microbiomes. Better understanding of the interplay between host hybridization and host-associated microbiomes has the potential to provide insight into both the roles of host-associated microbiomes as dictators of host performance as well as the fundamental rules governing host-associated microbiome assembly. Unfortunately, there is a current lack of frameworks for understanding the structure of host-associated microbiomes of hybrid organisms. In this paper, we develop four conceptual models describing possible relationships between the host-associated microbiomes of hybrids and their progenitor or ‘parent’ taxa. We then integrate these models into a quantitative ‘4H index’ and present a new R package for calculation, visualization, and analysis of this index. Finally, we demonstrate how the 4H index can be used to compare hybrid microbiomes across disparate plant and animal systems.
Noncanonical Rab9a action supports endosomal exit of human papillomavirus during virus entry
Authors: Choi Jeongjoon , DiMaio Daniel 
Published: May 2023

AbstractRab GTPases play key roles in controlling intracellular vesicular transport. GTP-bound Rab proteins support vesicle trafficking. Here, we report that, unlike cellular protein cargos, the delivery of human papillomaviruses (HPV) into the retrograde transport pathway during virus entry is inhibited by Rab9a in its GTP-bound form. Knockdown of Rab9a hampers HPV entry by regulating the HPV-retromer interaction and impairing retromer-mediated endosome-to-Golgi transport of the incoming virus, resulting in the accumulation of HPV in the endosome. Rab9a is in proximity to HPV as early as 3.5 h post-infection, prior to the Rab7-HPV interaction. HPV displays increased association with retromer in Rab9a knockdown cells, even in the presence of dominant negative Rab7. Thus, Rab9a can regulate HPV-retromer association independently of Rab7. Surprisingly, excess GTP-Rab9a impairs HPV entry, whereas excess GDP-Rab9a stimulates entry. These findings reveal that HPV employs a trafficking mechanism distinct from that used by cellular proteins.
Customer experience management in themed amusement parks: the impact of safety measures on the physical, social and digital servicescape of Gardaland Park
Authors: Bonfanti Angelo , Vigolo Vania , Gonzo Elisa , Genuardi Ileana 
Published: May 2023

Purpose
This study aims to examine the role of the servicescape in the customer experience management (CEM) of a themed amusement park following the COVID-19 pandemic. Considering the managers’ and customers’ perspectives, this study specifically addresses the following three research questions: first, What changes have occurred in the servicescape following the adoption of safety measures in the park in response to the COVID-19 pandemic? Second, What are the effects of these safety measures in relation to CEM? Third, What are the changes that could be maintained in the future to continue improving the customer experiential journey in the park?

Design/methodology/approach
A single case study method was adopted. Gardaland Park was selected as the case for this study. Data were collected from several sources: in-depth interviews with managers of Gardaland Park, focus group interviews with customers, and the corporate website and documentary. Reflexive thematic analysis was used to examine the data.

Findings
The findings reveal that safety measures affect the physical, social and digital (e- and smart) servicescape by influencing the aesthetic (reassurance), entertainment (relaxation), escapist (enjoyment and distraction) and educational (learning) experiences. Among the various changes implemented, the digital servicescape can be improved in the future when the pandemic is over by providing flexible solutions in relation to services at the park (e.g. virtual queuing) or on the website (e.g. dynamic booking).

Practical implications
The findings provide park managers with practical advice about servicescape organization to facilitate offering safe and memorable customer experiences.

Originality/value
To the best of the authors’ knowledge, this is the first study to address the effects of safety measures on the servicescape and CEM in themed amusement parks after the COVID-19 pandemic.