bluuebunny/crossref_metadata_2025 huggingface dataset:
Qipengyuania benthica sp. nov. and Qipengyuania profundimaris sp. nov., two novel Erythrobacteraceae members isolated from deep-sea environments
Authors: Wang Yuan , You Hao , Bu Yu-Xin , Zhou Peng , Xu Lin , Fu Ge-Yi , Xu Xue-Wei
Published: March 2024

Two Gram-stain-negative, rod-shaped and non-motile strains, designated as DY56-A-20T and G39T, were isolated from deep-sea sediment of the Pacific Ocean and deep-sea seawater of the Indian Ocean, respectively. Strain DY56-A-20T was found to grow at 15–37 °C (optimum, 28 °C), at pH 6.0–10.0 (optimum, pH 6.5–7.0) and in 0.5–6.0 % (w/v) NaCl (optimum, 1.0–2.0 %), while strain G39T was found to grow at 10–42 °C (optimum, 35–40 °C), at pH 5.5–10.0 (optimum, pH 6.5–7.0) and in 0–12.0 % (w/v) NaCl (optimum, 1.0–2.0 %). The 16S rRNA gene sequence identity analysis indicated that strain DY56-A-20T had the highest sequence identity with Qipengyuania marisflavi KEM-5T (97.6 %), while strain G39T displayed the highest sequence identity with Qipengyuania citrea H150T (98.8 %). The phylogenomic reconstruction indicated that both strains formed independent clades within the genus Qipengyuania. The digital DNA–DNA hybridization and average nucleotide identity values between strains DY56-A-20T/G39T and Qipengyuania/Erythrobacter type strains were 17.8–23.8 % and 70.7–81.1 %, respectively, which are below species delineation thresholds. The genome DNA G+C contents were 65.0 and 63.5 mol% for strains DY56-A-20T and G39T, respectively. The predominant cellular fatty acids (>10 %) of strain DY56-A-20T were C17 : 1
 ω6c, summed feature 8 and summed feature 3, and the major cellular fatty acids of strain G39T were C17 : 1
 ω6c and summed feature 8. The major polar lipids in both strains were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid and an unidentified polar lipid. The only respiratory quinone present in both strains was ubiquinone-10. Based on those genotypic and phenotypic results, the two strains represent two novel species belonging to the genus Qipengyuania, for which the names Qipengyuania benthica sp. nov. and Qipengyuania profundimaris sp. nov. are proposed. The type strain of Q. benthica is DY56-A-20T (=MCCC M27941T=KCTC 92309T), and the type strain of Q. profundimaris is G39T (=MCCC M30353T=KCTC 8208T).
Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases
Authors: Zhao Joseph J. , Ong Johnny Chin-Ann , Srivatsava Supriya , Ann Chia Daryl Kai , Ma Haoran , Huang Kiekyon , Sheng Taotao , Ramnarayanan Kalpana , Ong Xuewen , Tay Su Ting , Hagihara Takeshi , Keng Tan Angie Lay , Ching Teo Melissa Ching , Tan Qiu Xuan , Ng Gillian , Tan Joey Wee-Shan , Hsien Ng Matthew Chau , Gwee Yong Xiang , Walsh Robert , Shabbir Asim , Kim Guowei , Tay Yvonne , Her Zhisheng , Leoncini Giuseppe , Teh Bin Tean , Hong Jing Han , Kiat Tay Ryan Yong , Teo Chong Boon , Dings Mark P. G. , Bijlsma Maarten , Yew Lum Jeffrey Huey , Law Jia Hao , Pietrantonio Filippo , Blum Steven M. , van Laarhoven Hanneke , Klempner Samuel J. , Yong Wei Peng , Yan So Jimmy Bok , Chen Qingfeng , Tan Patrick , Sundar Raghav
Published: March 2024

Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis, yet our understanding of tumor microenvironmental (TME) characteristics associated with GCPM remain limited. Here, we analyzed intrinsic genomic alterations and transcriptomic programs predictive of GCPM in a prospective cohort of 248 patients, identifyingCDH1,PIGR, andELF3mutations as predictors. By inspecting the spatial dynamics of the TME, we find that tumor compartment infiltration of pro-tumorigenic cell types such as inflammatory cancer-associated fibroblasts (CAFs) predict peritoneal recurrence. Next, in a cross-sectional study of 205 samples from 55 patients, distinct pathways and immune compositions in GCPM relative to liver metastases highlight the TME’s significance in transcoelomic metastases. Notably, several putative therapeutic targets exhibited distinct expression patterns between PTs and PMs. We also observed increased immune infiltration in GCPMs treated with systemic immunotherapy and intraperitoneal chemotherapy. Our findings highlight transcriptomic variations and niche reprogramming in the GCPM peritoneal environment, revealing roles of myeloid dendritic cells, effector memory CD8+ T cells, and CAFs in metastatic progression.

Statement of significance

Comprehensive molecular profiling of gastric cancer primary and peritoneal tumors unveils crucial insights into the distinct molecular and immune landscape of peritoneal metastases. Identifying predictive markers and therapeutic targets emphasizes the significance of tumor microenvironment alterations in guiding future therapies for gastric cancer peritoneal metastasis.
SPACe (Swift Phenotypic Analysis of Cells): an open-source, single cell analysis of Cell Painting data
Authors: Stossi Fabio , Singh Pankaj K. , Marini Michela , Safari Kazem , Szafran Adam T. , Tostado Alejandra Rivera , Candler Christopher D. , Mancini Maureen G. , Mosa Elina A. , Bolt Michael J. , Labate Demetrio , Mancini Michael A.
Published: March 2024

Phenotypic profiling by high throughput microscopy has become one of the leading tools for screening large sets of perturbations in cellular models. Of the numerous methods used over the years, the flexible and economical Cell Painting (CP) assay has been central in the field, allowing for large screening campaigns leading to a vast number of data-rich images. Currently, to analyze data of this scale, available open-source software (i.e., CellProfiler) requires computational resources that are not available to most laboratories worldwide. In addition, the image-embedded cell-to-cell variation of responses within a population, while collected and analyzed, is usually averaged and unused. Here we introduce SPACe (SwiftPhenotypicAnalysis ofCells), an open source, Python-based platform for the analysis of single cell image-based morphological profiles produced by CP experiments. SPACe can process a typical dataset approximately ten times faster than CellProfiler on common desktop computers without loss in mechanism of action (MOA) recognition accuracy. It also computes directional distribution-based distances (Earth Mover’s Distance – EMD) of morphological features for quality control and hit calling. We highlight several advantages of SPACe analysis on CP assays, including reproducibility across multiple biological replicates, easy applicability to multiple (∼20) cell lines, sensitivity to variable cell-to-cell responses, and biological interpretability to explain image-based features. We ultimately illustrate the advantages of SPACe in a screening campaign of cell metabolism small molecule inhibitors which we performed in seven cell lines to highlight the importance of testing perturbations across models.
Optical Control of Cardiac Electrophysiology by the Photochromic Ligand AB2
Authors: Fehrentz Timm , Amin Ehsan , Görldt Nicole , Strasdeit Tobias , Moussavi-Torshizi S. Erfan , Leippe Philipp , Trauner Dirk , Meyer Christian , Frey Norbert , Sasse Philipp , Klöcker Nikolaj
Published: March 2024

Ventricular arrhythmias (VAs) may occur in both the structurally normal and diseased heart. Particularly, patients suffering from ischemic heart disease and heart failure are at high risk of recurrent VA eventually leading to sudden cardiac death (SCD). While high-voltage shocks delivered by an implantable defibrillator may prevent SCD, these interventions themselves impair quality of life and raise both morbidity and mortality, which accentuates the need for developing novel defibrillation techniques. Here, we report the photochromic ligand azobupivacaine 2 (AB2) to enable gradual control of cardiac electrophysiology by light. By reversibly blocking voltage-gated both Na+and K+channels, photoswitching of AB2 modulates both the ventricular effective refractory period and conduction velocity thereby converting VA into sinus rhythm in an ex-vivo intact heart model. Thus, AB2 opens the door to the development of an optical defibrillator based on photopharmacology.
Quantitative modelling of signaling in aggressive B cell lymphoma unveils conserved core network
Authors: Klinger Bertram , Rausch Isbael , Sieber Anja , Kutz Helmut , Kruse Vanessa , Kirchner Marieluise , Mertins Philipp , Kieser Arnd , Bluthgen Nils , Kube Dieter
Published: March 2024

B cell receptor (BCR) signaling is required for the survival and maturation of B cells and is deregulated in B cell lymphomas. While proximal BCR signaling is well studied, little is known about the crosstalk of downstream effector pathways, and a comprehensive quantitative network analysis of BCR signaling is missing. Here, we semi-quantitatively modelled BCR signaling in Burkitt lymphoma (BL) cells using systematically perturbed phosphorylation data of BL-2 and BL-41 cells. The models unveiled feedback and crosstalk structures in the BCR signaling network, including a negative crosstalk from p38 to MEK/ERK. The relevance of the crosstalk was verified for BCR and CD40 signaling in different BL cells and confirmed by global phosphoproteomics on ERK itself and known ERK target sites. Compared to the starting network, the trained network for BL-2 cells was better transferable to BL-41 cells. Moreover, the BL-2 network was also suited to model BCR signaling in Diffuse large B cell lymphoma cells lines with aberrant BCR signaling (HBL-1, OCI-LY3), indicating that BCR aberration does not cause a major downstream rewiring.
A dynamin-like protein in the human malaria parasite plays an essential role in mitochondrial homeostasis and fission during asexual blood stages
Authors: Thakur Vandana , Singh Shweta , Rathore Sumit , Muneer Azhar , Islam Md. Muzahidul , Dutta Gaurav , Banday Mudassir M. , Arora Priya , Hossain Mohammad E. , Jain Shaifali , Ali Shakir , Mohmmed Asif
Published: March 2024

Malaria parasite harbors a single mitochondrion and its proper segregation during the parasite multiplication is crucial for propagation of the parasite within the host. Mitochondrial fission machinery consists of a number of proteins that associate with mitochondrial membrane during segregation. Here, we have identified a dynamin-like protein inP. falciparum,PfDyn2, and deciphered its role in mitochondrial division, segregation and homeostasis. GFP targeting approach combined with high resolution microscopy studies showed that thePfDyn2 associates with mitochondrial membrane to form a clip/hairpin loop like structure around it at specific sites during mitochondrial division. The C-terminal degradation tag mediated inducible knock-down (iKD) ofPfDyn2 resulted in significant inhibition of parasite growth.PfDyn2-iKD hindered mitochondrial development and functioning, decreased mtDNA replication, and induced mitochondrial oxidative-stress, ultimately causing parasite death. Further, treatment of parasites with dynamin specific inhibitors disrupted the recruitment ofPfDyn2 on the mitochondria, blocked mitochondrial development, and induced oxidative stress. Regulated overexpression of a phosphorylation mutant ofPfDyn2 (Ser-612-Ala) had no effect on the recruitment ofPfDyn2 on the mitochondria; normal mitochondrial division and parasite growth showed that phosphorylation/dephosphorylation of this conserved serine residue (Ser612) may not be responsible for regulating recruitment ofPfDyn2 to the mitochondrion. Overall, we show essential role ofPfDyn2 in mitochondrial dynamics and fission as well as in maintaining its homeostasis during asexual cycle of the parasite.
Analytical Methods and Platforms for circRNA Vector Engineering to Improve Circularization Efficiency
Authors: Sun Yali , Khimani Anis H. , Tong Yanhong , Lu Zhi-xiang
Published: March 2024

Circular RNAs (circRNAs) have emerged as pivotal players in RNA therapeutics. Unlike linear counterparts, circRNAs possess a closed-loop structure, conferring them with enhanced stability and resistance to degradation. This resilience makes them promising candidates for diagnostic and therapeutic applications. The ribozyme-based strategy stands out as the predominant method for synthetic circRNA production. In this strategy, ribozymes (catalytic RNA molecules) facilitate the circularization process by precisely cleaving and promoting the formation of a covalent circular structure. In the report, we detail analytical methods for circRNA vector engineering to enhance circularization efficiency. This approach will capture the attention of researchers interested in optimizing RNA circularization efficiency, as well as those focused on exploring key elements for ribozyme catalytic activity.
Engineering Substrate Channeling in Assembly-Line Terpene Biosynthesis
Authors: Wenger Eliott S. , Schultz Kollin , Marmorstein Ronen , Christianson David W.
Published: March 2024

Fusicoccadiene synthase fromP. amygdala(PaFS) is a bifunctional assembly-line terpene synthase containing a prenyltransferase domain that generates geranylgeranyl diphosphate (GGPP) from dimethylallyl diphosphate (DMAPP) and three equivalents of isopentenyl diphosphate (IPP), and a cyclase domain that converts GGPP into fusicoccadiene, a precursor of the diterpene glycoside Fusicoccin A. The two catalytic domains are linked by a flexible 69-residue polypeptide segment. The prenyltransferase domain mediates oligomerization to form predominantly octamers, and cyclase domains are randomly splayed out around the prenyltransferase core. Previous studies suggest that substrate channeling is operative in catalysis, since most of the GGPP formed by the prenyltransferase remains on the protein for the cyclization reaction. Here, we demonstrate that the flexible linker is not required for substrate channeling, nor must the prenyltransferase and cyclase domains be covalently linked to sustain substrate channeling. Moreover, substrate competition experiments with other diterpene cyclases indicate that the PaFS prenyltransferase and cyclase domains are preferential partners regardless of whether they are covalently linked or not. The cryo-EM structure of engineered “linkerless” construct PaFSLL, in which the 69-residue linker is spliced out and replaced with the tripeptide PTQ, reveals that cyclase pairs associate with all four sides of the prenyltransferase octamer. Taken together, these results suggest that optimal substrate channeling is achieved when a cyclase domain associates with the side of the prenyltransferase octamer, regardless of whether the two domains are covalently linked and regardless of whether this interaction is transient or locked in place.
Matrisome gene expression is altered during non-allometric heart growth in genetically enlargedDrosophila
Authors: Andrews Rachel M. , Jacobs J. Roger
Published: March 2024

The cardiac extracellular matrix (ECM) is critical to defining the biophysical properties of the heart that adapt to changing stresses with growth or disease. The ECM is commonly dysregulated in chronic disease such as hypertension, diabetes, and cardiomyopathies, often leading to the development of fibrosis. There are no treatment options to address most ECM cardiomyopathies, but developing therapeutic targets necessitates an understanding of the regulation of ECM remodelling. Here, we employ a larvalDrosophilaovergrowth model (“giant larvae”) to overload the heart and alter ECM remodellingin vivo. These larvae grow to immense sizes without exhibiting hallmarks of obesity. Remarkably, cardiac ECM organization scales allometrically despite overload. The main effect observed is a change in Collagen fibril thickness, possibly reflecting changes to tension in the system. Overgrowth-induced changes in gene expression similarly suggest changes in Collagen assembly, such as a dramatic increase in LOXL2, the main Collagen crosslinking enzyme. This could indicate that larvae may compensate for the stress of overgrowth by stabilizing the Collagen network. The enlarged hearts of giant larvae cannot contract fully at systole. Taken together, this reveals non-allometric changes to cardiac form and output with increasing body size. Overall, our overgrowth model presents an intriguing opportunity to examine the ability of a system to tolerate overgrowth without the metabolic inputs of obesity.
Stochastic variation in the FOXM1 transcription program mediates replication stress tolerance
Authors: Segeren Hendrika A. , Wierenga Kathryn A. , Riemers Frank M. , van Liere Elsbeth A. , Westendorp Bart
Published: March 2024

Oncogene-induced replication stress (RS) is a vulnerability of cancer cells that forces reliance on the intra-S-phase checkpoint to ensure faithful genome duplication. Inhibitors of the crucial intra-S-phase checkpoint kinases ATR and CHK1 have been developed, but persistent proliferation and resistance to these drugs remain problematic. Understanding drug tolerance mechanisms is impeded by analysis of bulk samples, which neglect tumor heterogeneity and often fail to accurately interpret cell cycle-mediated resistance. Here, by combining intracellular immunostaining and RNA-sequencing of single cells, we characterized the transcriptomes of oncogenic RAS-expressing cells that exhibit variable levels of RS when challenged with a CHK1 inhibitor in combination with the chemotherapeutic drug gemcitabine. We identified 40 genes differentially expressed between tolerant and sensitive cells, including several FOXM1 target genes. While complete knockdown ofFOXM1impeded cell proliferation, a partial knockdown protected cells against DNA damage, and improved recovery from drug-induced RS. Our results suggest that low levels of FOXM1 expression protects subsets of oncogenic RAS-expressing cells against DNA damage during drug-induced replication stress.
Single-cell transcriptomics identifies a p21-activated kinase important for survival of the zoonotic parasiteFasciola hepatica
Authors: Puckelwaldt Oliver , Gramberg Svenja , Ajmera Sagar , Koepke Janine , Samakovlis Christos , Haeberlein Simone
Published: March 2024

Knowledge on the cell types and cell-specific gene expression of multicellular pathogens facilitates drug discovery and allows gaining a deeper understanding of pathogen biology. By utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 19,581 cells of a globally prevalent parasitic flatworm, the liver fluke Fasciola hepatica, which causes a neglected tropical disease and zoonosis known as fascioliasis. We identified 15 distinct clusters, including cells of the reproductive tract and gastrodermis, and report the identification and transcriptional characterization of potential differentiation lineages of stem cells within this parasite. Furthermore, a previously unrecognized ELF5- and TRPMPZQ-expressing muscle cell type was discovered, characterized by high expression of protein kinases. Among these, the p21-activated kinase PAK4 was essential for parasite survival. These data provide novel insight into the cellular composition of a complex multicellular parasite and demonstrate how gene expression at single-cell resolution can serve as a resource for the identification of new drug targets.
Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence
Authors: Aikins Muna , Willems Yayouk , Mitchell Colter , Goosby Bridget , Raffington Laurel
Published: March 2024

Marginalization due to structural racism may confer an increased risk for aging-related diseases – in part – via effects on people’s mental health. Here we leverage a prospective birth cohort study to examine whether the emergence of racial disparities in mental health and DNA-methylation measures of biological aging (i.e., DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration) are linked across childhood and adolescence. We further consider to what extent racial disparities are statistically accounted for by perinatal and postnatal factors in preregistered analyses of N=4,898 participants from the Future of Families & Child Wellbeing Study, of which N=2,039 had repeated saliva DNA methylation at ages 9 and 15 years. We find that racially marginalized children had higher levels of externalizing and internalizing behaviors and diverging longitudinal internalizing slopes. Black compared to White identifying children, children living in more racially segregated neighborhoods, and racially marginalized children more affected by colorism tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. Notably, longitudinal increases in internalizing and externalizing behavior were correlated with longitudinal increases in biological aging. While racial and ethnic disparities in mental health were largely statistically accounted for by socioeconomic variables, racial differences in biological aging were often still visible beyond covariate controls. Our findings indicate that racial disparities in mental health and biological aging are linked and emerge early in life. Programs promoting racial health equity must address the psychological and physical impacts of structural racism in children. Comprehensive measures of racism are lacking in current population cohorts.
Repetitive head impacts induce neuronal loss and neuroinflammation in young athletes
Authors: Butler Morgane L.M.D. , Pervaiz Nida , Breen Kerry , Calderazzo Samantha , Ypsilantis Petra , Wang Yichen , Breda Julia Cammasola , Mazzilli Sarah , Nicks Raymond , Spurlock Elizabeth , Hefti Marco M. , Fiock Kimberly L. , Huber Bertrand R. , Alvarez Victor E. , Stein Thor D. , Campbell Joshua D. , McKee Ann C. , Cherry Jonathan D.
Published: March 2024

Repetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear. Further, the symptoms endorsed by young individuals with early disease are not fully explained by the extent of p-tau deposition, severely hampering development of therapeutic interventions. Here, we show that RHI exposure associates with a multicellular response in young individuals (<51 years old) prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure. Leveraging single nucleus RNA sequencing of tissue from 8 control, 9 RHI-exposed, and 11 low stage CTE individuals, we identify SPP1+ inflammatory microglia, angiogenic and inflamed endothelial cell profiles, reactive astrocytes, and altered synaptic gene expression in excitatory and inhibitory neurons in all individuals with exposure to RHI. Surprisingly, we also observe a significant loss of cortical sulcus layer 2/3 neurons in contact sport athletes compared to controls independent of p-tau pathology. Finally, we identify TGFB1 as a potential signal mediating microglia-endothelial cell cross talk through ligand-receptor analysis. These results provide robust evidence that multiple years of RHI exposure is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early pathogenesis in young former contact sport athletes. Furthermore, these data identify specific cellular responses to repetitive head impacts that may direct future identification of diagnostic and therapeutic strategies for CTE.
The plant specific cohesin subunit SYN4 contributes to 3D genome organization
Authors: Paajanen Pirita , Proksch Carsten , Krüger Sylvia , Gorzolka Karin , Ziegler Jörg , Romeis Tina , Dodd Antony N. , Bomblies Kirsten , Handrick Vinzenz
Published: March 2024

Chromatin architecture in the cells of animals and fungi influences gene expression. The molecular factors that influence higher genome architecture in plants and their effects on gene expression remain unknown. Cohesin complexes, conserved in eukaryotes, are essential factors in genome structuring. Here, we investigated the relevance of the plant-specific somatic cohesin subunit SYN4 for chromatin organisation inArabidopsis thaliana.

Plants mutated inSYN4were studied using HRM, Hi-C, RNA sequencing, untargeted and targeted metabolomics and physiological assays to understand the role of this plant-specific cohesin.

We show thatsyn4mutants exhibit altered intra- and interchromosomal interactions, expressed as sharply reduced contacts between telomeres and chromosome arms but not between centromeres, and differences in the placement and number of topologically associated domains (TADs)-like structures. By transcriptome sequencing, we also show thatsyn4mutants have altered gene expression, including numerous genes that control abiotic stress responses.

The response to drought stress inArabidopsisis strongly influenced by the genome structure insyn4mutants, potentially due to altered expression ofCYP707A3, an ABA 8’-hydroxylase.

In brief

The 3D architecture of the genome extensively influences gene expression in animals and fungi. We show that the plant-specific cohesin subunit SYN4 affects intra- and interchromosomal interactions including telomere clustering, with consequences for the expression of genes of transient and induced biological pathways and the biosynthesis of bioactive compounds. Highly condensed genome structures at theCYP707A3locus positively affects the stress response to water deprivation regulated by abscisic acid.
Type 1 diabetes and parasite infection: an exploratory study in the NOD mouse
Authors: Giraud Emilie , Fiette Laurence , Melanitou Evie
Published: March 2024

Microorganisms have long been suspected to influence the outcome of immune-related syndromes, particularly autoimmune diseases. Type 1 diabetes (T1D) results from the autoimmune destruction of the pancreatic islets’ insulin-producing beta cells, causing high glycemia levels. Genetics is part of its etiology, but environmental factors, particularly infectious microorganisms, also play a role.

It was shown that bacteria, viruses, and parasites, influence the outcome of T1D in mice and humans. We have used the Non-Obese Diabetic (NOD) mouse that spontaneously develops T1D to address the influence of a parasitic infection, leishmaniasis.Leishmania amazonensisare intracellular eukaryotic parasites replicating predominantly in macrophages and are responsible for cutaneous leishmaniasis. The implication of Th1 immune responses in T1D and leishmaniasis led us to study this parasite in the NOD mouse model. We have previously constructed osteopontin knockout mice in an NOD genetic background and demonstrated that this protein plays a role in the T1D phenotype. In addition, osteopontin (OPN) has been found i) to play a role in the immune response to various infectious microorganisms and ii) to be implicated in other autoimmune conditions, such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in mice.

We present herein data demonstrating the implication of OPN in the response toLeishmaniain the NOD mouse and the influence of this parasitic infection on T1D. This exploratory study aims to investigate the environmental infectious component of the autoimmune response, including through Th1 immunity, common to both T1D and leishmaniasis.
Insulation of ribosomal promoter activity by Fis, H-NS or a divergent promoter within the packed E. coli genome.
Authors: Brambilla Elisa , Yousuf Malikmohamed , Zhang Qing , Mbemba Gladys , Oeuvray Cyriane , Mektepbayeva Damel , Olliver Anne , Lagomarsino Marco Cosentino , Sclavi Bianca
Published: March 2024

Gene expression in bacterial cells is dependent on a gene&prime s position along the genome, mainly because of the effects of neighbouring genes&prime expression, but also because of the local activity of nucleoid proteins, differing levels of DNA supercoiling and changes in gene copy number with growth rate and growth phase. This genome position dependence can be a source of specific regulation, however, in some cases it is necessary to have gene expression insulated from these local effects. Escherichia coli cells express ribosomal RNA from multiple operons found at different sites along the genome. The number of ribosomal operons varies in different strains and correlates with the maximal growth rate. rRNA promoters are under the regulation of Fis, H-NS, DNA supercoiling and ppGpp. These factors are known to result in growth phase and growth rate dependent regulation of gene expression. Here we show that the combined action of Fis and H-NS also provides insulation from the activity of both local and global regulatory factors. Furthermore, our results indicate that the presence of a divergently expressed gene can also act as an insulator revealing a DNA supercoiling gradient from the origin to the terminus. The organisation of ribosomal promoters therefore has been selected to allow for gene duplication independently of the influence of local genome organisation and neighbouring genes&prime activity.
Developing a multidimensional risk assessment model for sustainable construction projects
Authors: Wuni Ibrahim Yahaya
Published: March 2024

Purpose

Sustainable construction re-engineers the conventional project lifecycle to integrate sustainability solutions. The additional sustainability requirements introduce new layers of complexity, challenges and risks that if unaddressed, can derail the gains in sustainable construction projects. This study developed a multidimensional risk assessment model for sustainable construction projects in the United Arab Emirates (UAE).

Design/methodology/approach

The research activities a comprised comprehensive literature review to shortlist relevant risks, an analysis of the probability – impact rating of the shortlisted risks – and the development of a risk assessment model for SC projects in the UAE. The model is developed based on the multicriteria framework and mathematical formulation of the fuzzy synthetic evaluation approach.

Findings

The developed model quantified the overall risk level in sustainable construction projects to be 3.71 on a 5-point Likert scale, indicating that investment in SC projects in the UAE is risky and should be carefully managed. The developed model further revealed that each of the risk groups, comprising management (3.82), technical (3.78), stakeholder (3.68), regulatory (3.66), material (3.53) and economic risks (3.502), presents a significant threat to realizing outcomes typical of SC projects.

Originality/value

This study developed a multidimensional risk assessment model capable of objectively quantifying the overall risk level and provides decision support to project teams to improve risk management in sustainable construction projects.
Hybrid entrepreneurship, job satisfaction and the spillover effect of creativity
Authors: Crider Cole J. , Aghaey Alireza , Lortie Jason , Peake Whitney O. , Digan Shaun
Published: March 2024

Purpose

The purpose of this study is to empirically examine how individuals’ hybrid entrepreneurial venturing activities (HEVA) influence key characteristics associated with one’s wage work, namely creativity and job satisfaction.

Design/methodology/approach

Through a cross-sectional self-administered survey design, data were gathered from 465 US-based useable responses via Amazon Mechanical Turk and analyzed using structural equation modeling (SEM).

Findings

Findings show individuals reporting higher levels of HEVA – such as creating, founding, starting or running – tend to also exhibit higher levels of creativity and job satisfaction in their workplaces. Findings further reveal that income negatively moderates the relationship between creativity and wage work job satisfaction.

Practical implications

By providing a better understanding of how engaging in HEVA can impact creativity and job satisfaction, this study has important implications for (1) managers seeking to influence key employee outcomes and (2) employees considering such entrepreneurial activities.

Originality/value

This paper adds to the growing scholarly and practitioner interest in hybrid entrepreneurship and its outcomes. Specifically, the paper adds new insights regarding how engaging in HEVA can influence individual skills (i.e. creativity) or organizational goals (i.e. employee job satisfaction). In doing so, the paper also uses insights from the intrinsic/extrinsic motivation literature to suggest how extrinsic motivators (such as income) can interact with intrinsically motivated behaviors (such as creativity) in influencing employee outcomes in wage work. Finally, the paper contributes to the growing interest in applying the empowerment perspective within entrepreneurship research by exploring where and how empowerment may occur.
Labour mobility, short-time work and working from home: establishments' behaviour during the COVID-19 crisis
Authors: Bellmann Lisa , Bellmann Lutz , Hübler Olaf
Published: March 2024

Purpose

We enquire whether short-time work (STW) avoids firings as intended by policymakers and is associated with unintended side effects by subsidising some establishments and locking in some employees. Additionally, where it was feasible, establishments used working from home (WFH) to continue working without risking an increase in COVID-19 infections and allowing employed parents to care for children attending closed schools.

Design/methodology/approach

Using 21 waves of German high-frequency establishment panel data collected during the COVID-19 crisis, we investigate how STW and WFH are associated with hirings, firings, resignations and excess labour turnover (or churning).

Findings

Our results show the important influences of STW and working from home on employment dynamics during the pandemic. By means of STW, establishments are able to avoid an increase in involuntary layoffs and hiring decreases significantly. In contrast, WFH is associated with a rise in resignations, as can be expected from a theoretical perspective.

Originality/value

While most of the literature on STW and WFH is unrelated and remains descriptive, we consider them in conjunction and conduct panel data analyses. We apply data and methods that allow for the dynamic pattern of STW and working from home during the pandemic. Furthermore, our data include relevant establishment-level variables, such as the existence of a works council, employee qualifications, establishment size, the degree to which the establishment was affected by the COVID-19 crisis, industry affiliation and a wave indicator for the period the survey was conducted.
From virtual reality to cultural reality: integration of virtual reality into teaching culture in foreign language education
Authors: Tafazoli Dara
Published: March 2024

Purpose

This research paper aimed to investigate the affordances of using virtual reality (VR) in teaching culture among in-service teachers of teaching Persian to speakers of other languages (TPSOL) in Iran.

Design/methodology/approach

This qualitative case study, conducted at two Iranian universities, used purposeful sampling to select 34 eligible in-service Persian teachers from a pool of 73. Data collection used an open-ended questionnaire and interviews.

Findings

Before the TPSOL in-service training workshop, teachers expressed their reservations regarding the use of VR to teach culture in TPSOL courses. The emerged themes were “skepticism toward effectiveness,” “practicality concerns,” “limited awareness of VR applications,” “technological apprehension” and “prevalence of traditional teaching paradigms.” During the post-workshop interview, it was discovered that the teachers’ perceptions of VR in teaching culture had undergone a positive shift. The workshop generated emergent themes that reflected positive perceptions and affordances for using VR to teach culture in TPSOL, including “enhanced cultural immersion,” “increased student engagement,” “simulation of authentic cultural experiences,” and “facilitation of interactive learning environments.”

Research limitations/implications

One primary limitation is the lack of prior experience with VR for teaching practices in real-world classrooms among the participants. While the study aimed to explore the potential of VR in enhancing pedagogical approaches, the absence of participants with prior exposure to VR in educational contexts may impact the generalizability of the findings to a broader population. Additionally, the study faced practical constraints, such as the unavailability of sufficient facilities in the workshop. As a result, the instructor had to project the VR cont7ent on a monitor, potentially diverging from the immersive nature of true VR experiences. These limitations offer opportunities for future research to refine methodologies and gain a more comprehensive understanding of the implications of integrating VR into teaching practices.

Originality/value

Extensive research has been conducted on the effectiveness of VR in language education. However, there is a significant gap in research on TPSOL, which is considered a less commonly taught language. This study aims to address this gap by exploring the use of VR in the TPSOL through the lenses of in-service teachers. As part of a larger investigation, this qualitative inquiry focuses on the perceptions of in-service teachers about VR, with a particular emphasis on the cultural understanding of the Persian language.
Analyzing the drivers of blockchain adoption for supply chain in Pakistan
Authors: Khalil Muhammad Mohsin , Ahmed Waqar
Published: March 2024

Purpose

In recent years, technological advancement has played a crucial role in the growth of emerging economies. However, as with any novel technological development, there are often concerns and hesitations surrounding its implementation. This study aims to investigate the factors influencing blockchain adoption and usage. Thereby evaluating its impact on supply chain performance.

Design/methodology/approach

This is a deductive research based on the modified form unified theory of acceptance and use of technology, which is a persuasive model that has been used in numerous studies on the acceptance and usage of information technology systems. For this study, valid data was collected from 129 management-level supply chain professionals and policymakers working in diverse manufacturing industries. The collected data was used for testing hypotheses by deploying the structural equation modeling technique.

Findings

The findings of this study reveal that facilitating conditions and technology readiness highly are key influencers for organizations to implement this disruptive technology. Moreover, blockchain adoption and usage can significantly enhance supply chain performance.

Originality/value

Blockchain technology is a novel and promising disruptive technology that industries are looking forward to adopting and using. For the policymakers and supply chain strategists working in a developing country, this study offers a comprehensive viewpoint on the swift acceptance and usage of blockchain technology to facilitate supply chain operations.
China's Media Warfare
Authors: Hilton Isabel
Published: March 2024

This article examines China's efforts to establish global discourse control through investment in its own global media and establishing relationships with existing media in both Western liberal democracies and emerging economies.
The Historic, Present and Future Role of Regulation in Securing the Standards of ‘Public Value’ Media
Authors: Hughes Jacquie
Published: March 2024

This article examines the evolution of public service broadcasting (PSB) regulation in the UK, contrasting two opposing perspectives on its role and addressing its contemporary challenges. Analysing the historical context and recent regulatory changes, the article argues that PSB remains vital to the UK's media landscape, providing high quality content and serving the public good. However, it identifies technological advancements and political interference as significant threats to its continued success. The article critically evaluates the draft Media Bill's potential to address these challenges and enhance PSB's competitiveness. Additionally, it raises concerns about potential bias within the regulatory body, Ofcom, urging greater transparency and fairness in its oversight of the media market. The article emphasises the need for a robust regulatory framework to ensure the continued viability of PSB and foster a vibrant and diverse media ecosystem.
BBC Funding: Much Ado about the Cost of a Coffee a Week
Authors: Barwise Patrick
Published: March 2024

BBC funding (the licence fee model and the funding level) has been turned into a big issue out of all proportion to the low financial stakes—equivalent to the cost of one takeaway coffee a week for the whole household, excluding those with free TV licences. This article first proposes and explores three possible reasons for all the fuss: that licence payers take the BBC for granted, underestimating the value they get from it; that the attacks on BBC funding are part of a wider ‘war’ against it, driven by commercial or political vested interests; and that at least some of the criticisms of the licence fee reflect genuine, although much exaggerated, disadvantages. The article then evaluates four alternative funding models: advertising, subscriptions, general taxation and a universal household levy. It argues that the best long‐term model would be a flat, universal household levy, with exemptions for those least able to pay, as in Germany, with the funding level set by an independent body organised by Ofcom; and that, because the licence fee is becoming harder to sustain, this new funding model should be introduced at the start of the next BBC Charter in January 2028.
Micromonas, a small pigmented flagellate, predominates the nanoflagellate and photosynthetic picoeukaryote communities in the northern South China Sea
Authors: Guo Xin , Pang Mengwen , Zheng Xinyi , Huang Lingfeng
Published: March 2024

A small pigmented flagellate, Micromonas, is prevalently distributed in coastal and pelagic waters. However, there have been few studies conducted to quantify their abundance in the marginal seas of the Northwest Pacific Ocean. In this study, we used fluorescent in situ hybridization with tyramide signal amplification (TSA‐FISH) to reveal the spatial distribution of Micromonas in the northern South China Sea (SCS). On average, the abundance of Micromonas was 317 cells mL−1, with the average proportions in the nanoflagellates (NF) and photosynthetic picoeukaryotes (PPE) communities being 10.94% and 15.39%, respectively. This indicates a wide distribution and dominance of this genus in the studied area. The relationships between Micromonas abundance and various environmental factors suggested that biotic correlations play more important roles than physicochemical filtering on Micromonas assemblage. This may indicate a broad environmental adaptation spectrum of this genus through its flexibility in terms of resource acquisition strategies. In summary, this study provides insight into the spatial distribution pattern of Micromonas and highlights its crucial contribution to the composition of NFs and PPE communities, which rely on biological interaction to respond to the changing environmental conditions in the northern SCS.
Screening performance of a 100‐mL water swallowing test in community‐dwelling older adults: A receiver operating characteristic analysis
Authors: Yamabe Kazumi , Nishida Takahiro , Ide Yoshihiko , Honda Sumihisa
Published: March 2024

Objective

The development of a dysphagia screening test is an urgent issue in the field of frailty prevention among community‐dwelling older people. The purpose of this study was to evaluate the screening performance of a 100‐mL water swallowing test (WST).

Methods

The study employed a cross‐sectional design. Participants were 304 (65 men and 239 women, mean age = 80 years) Japanese community‐dwelling older adults aged over 65 years. We investigated swallowing disorder using the 10‐item Eating Assessment Tool (EAT‐10), and compared choking signs, swallowing time and number of swallows, and their combination in the 100‐mL WST. We calculated the sensitivity and specificity of these indices. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut‐off value of swallowing time and number of swallows in the 100‐mL WST based on the Youden Index among participants without choking signs.

Results

The sensitivity and specificity of choking signs in the 100‐mL WST were 20% and 91%, respectively. The discriminating ability of swallowing time and number of swallows among participants without any choking signs was .76 and .72, respectively, in the area under the ROC curve. Diagnostic sensitivity and specificity to discriminate dysphagia from normal swallowing ability were 65% and 74% when the cut‐off was >10 s based on maximisation of the Youden Index. The 100‐mL WST performed best when the indices of choking signs and swallowing time were combined, with a sensitivity and specificity of 72% and 68%, respectively.

Conclusions

The 100‐mL WST would be an adequate screening tool when compared to the EAT‐10.
Gestational cholestyramine treatment protects adult offspring of ApoE‐deficient mice against maternal‐hypercholesterolemia‐induced atherosclerosis
Authors: Habib Marina , Croyal Mikael , Kaeffer Bertrand , Grit Isabelle , Castellano Blandine , Gourdel Mathilde , Le May Cédric , Thorin Chantal , Nazih Hassan , Ouguerram Khadija
Published: March 2024

Aim

Perinatal hypercholesterolemia exacerbates the development of atherosclerotic plaques in adult offspring. Here, we aimed to study the effect of maternal treatment with cholestyramine, a lipid‐lowering drug, on atherosclerosis development in adult offspring of hypercholesterolemic ApoE‐deficient (ApoE−/−) mice.

Methods

ApoE−/− mice were treated with 3% cholestyramine (CTY) during gestation (G). After weaning, offspring (CTY‐G) were fed control diet until sacrificed at 25weeks of age. Atherosclerosis development in the aortic root of offspring was assessed after oil‐red‐o staining, along with some of predefined atherosclerosis regulators such as LDL and HDL by high‐performance liquid chromatography (HPLC), and bile acids (BA) and trimethylamine N‐oxide (TMAO) by liquid chromatography‐mass spectrometry (LC–MS/MS).

Results

In pregnant dams, cholestyramine treatment resulted in significantly lower plasma total‐ and LDL‐cholesterol as well as gallbladder total BA levels. In offspring, both males and females born to treated dams displayed reduced atherosclerotic plaques areas along with less lipid deposition in the aortic root. No significant change in plasma total cholesterol or triglycerides was measured in offspring, but CTY‐G males had increased HDL‐cholesterol and decreased apolipoproteins B100 to A‐I ratio. This latter group also showed reduced gallbladder total and specifically tauro‐conjugated bile acid pools, whereas for CTY‐G females, hydrophilic plasma tauro‐conjugated BA pool was significantly higher. They also benefited from lower plasma TMAO.

Conclusion

Prenatal cholestyramine treatment reduces atherosclerosis development in adult offspring of ApoE−/− mice along with modulating the plaques' composition as well as some related biomarkers such as HDL‐C, bile acids and TMAO.