bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic control of germ layer proportions through regulation of Nodal and Wnt signalling
Authors: Stapornwongkul Kristina S. , Hahn Elisa , Palau Laura Salamo , Arato Krisztina , Gritti Nicola , Anlas Kerim , Poliński Patryk , Lopez Mireia Osuna , Eibisuya Miki , Trivedi Vikas
Published: December 2023

During embryonic development, cells exit pluripotency to give rise to the three germ layers. Metabolic pathways influence cell fate decisions by modulating the epigenetic, transcriptional, and signalling states of cells. However, the interplay between metabolism and the major signalling pathways that drive the emergence of ectoderm, mesoderm, and endoderm remains poorly understood. Here, we demonstrate an instructive role of glycolytic activity in activating signalling pathways involved in mesoderm and endoderm induction. Using an in vitro model system for mouse gastrulation, we observed that inhibiting glycolysis prevents the upregulation of primitive streak markers, resulting in a significant increase in ectodermal cell fates at the expense of mesodermal and endodermal lineages. We demonstrate that this relationship is dose-dependent, enabling metabolic control of germ layer proportions through exogenous glucose levels. Mechanistically, we found that glycolysis inhibition leads to the downregulation of Wnt, Nodal, and Fgf signalling. Notably, this metabolic phenotype was rescued by Nodal or Wnt signalling agonists in the absence of glycolytic activity, suggesting that glycolytic activity acts upstream of both signalling pathways. Our work underscores the dependence of specific signalling pathways on metabolic conditions and provides mechanistic insight into the nutritional regulation of cell fate decision making.
An evolution-based framework for describing human gut bacteria
Authors: Doran Benjamin A. , Chen Robert Y. , Giba Hannah , Behera Vivek , Barat Bidisha , Sundararajan Anitha , Lin Huaiying , Sidebottom Ashley , Pamer Eric G. , Raman Arjun S.
Published: December 2023

The human gut microbiome contains many bacterial strains of the same species (‘strain-level variants’). Describing strains in a biologically meaningful way rather than purely taxonomically is an important goal but challenging due to the genetic complexity of strain-level variation. Here, we measured patterns of co-evolution across >7,000 strains spanning the bacterial tree-of-life. Using these patterns as a prior for studying hundreds of gut commensal strains that we isolated, sequenced, and metabolically profiled revealed widespread structure beneath the phylogenetic level of species. Defining strains by their co-evolutionary signatures enabled predicting their metabolic phenotypes and engineering consortia from strain genome content alone. Our findings demonstrate a biologically relevant organization to strain-level variation and motivate a new schema for describing bacterial strains based on their evolutionary history.

One Sentence Summary

Describing bacterial strains in the human gut by a statistical model that captures their evolutionary history provides insight into their biology.
Multiplexed RNA-FISH-guided Laser Capture Microdissection RNA Sequencing Improves Breast Cancer Molecular Subtyping, Prognostic Classification, and Predicts Response to Antibody Drug Conjugates
Authors: Paul Evan D. , Huraiová Barbora , Valková Natália , Birknerova Natalia , Gábrišová Daniela , Gubova Sona , Ignačáková Helena , Ondris Tomáš , Bendíková Silvia , Bíla Jarmila , Buranovská Katarína , Drobná Diana , Krchnakova Zuzana , Kryvokhyzha Maryna , Lovíšek Daniel , Mamoilyk Viktoriia , Mančíková Veronika , Vojtaššáková Nina , Ristová Michaela , Comino-Méndez Iñaki , Andrašina Igor , Morozov Pavel , Tuschl Thomas , Pareja Fresia , Čekan Pavol
Published: December 2023

On a retrospective cohort of 1,082 FFPE breast tumors, we demonstrated the analytical validity of a test using multiplexed RNA-FISH-guided laser capture microdissection (LCM) coupled with RNA-sequencing (mFISHseq), which showed 93% accuracy compared to immunohistochemistry. The combination of these technologies makes strides in i) precisely assessing tumor heterogeneity, ii) obtaining pure tumor samples using LCM to ensure accurate biomarker expression and multigene testing, and iii) providing thorough and granular data from whole transcriptome profiling. We also constructed a 293-gene intrinsic subtype classifier that performed equivalent to the research based PAM50 and AIMS classifiers. By combining three molecular classifiers for consensus subtyping, mFISHseq alleviated single sample discordance, provided near perfect concordance with other classifiers (κ > 0.85), and reclassified 30% of samples into different subtypes with prognostic implications. We also use a consensus approach to combine information from 4 multigene prognostic classifiers and clinical risk to characterize high, low, and ultra-low risk patients that relapse early (< 5 years), late (> 10 years), and rarely, respectively. Lastly, to identify potential patient subpopulations that may be responsive to treatments like antibody drug-conjugates (ADC), we curated a list of 92 genes and 110 gene signatures to interrogate their association with molecular subtype and overall survival. Many genes and gene signatures related to ADC processing (e.g., antigen/payload targets, endocytosis, and lysosome activity) were independent predictors of overall survival in multivariate Cox regression models, thus highlighting potential ADC treatment-responsive subgroups. To test this hypothesis, we constructed a unique 19-feature classifier using multivariate logistic regression with elastic net that predicted response to trastuzumab emtansine (T-DM1; AUC = 0.96) better than eitherERBB2mRNA or Her2 IHC alone in the T-DM1 arm of the I-SPY2 trial. This test was deployed in a research-use only format on 26 patients and revealed clinical insights into patient selection for novel therapies like ADCs and immunotherapies and de-escalation of adjuvant chemotherapy.
SARS-CoV-2 Infection is Associated with an Increase in New Diagnoses of Schizophrenia Spectrum and Psychotic Disorder: A Study Using the US National COVID Cohort Collaborative (N3C)
Authors: Rahman Asif , Russell Michael , Zheng Wanhong , Eckrich Daniel , Ahmed Imtiaz
Published: December 2023

Amid the ongoing global repercussions of SARS-CoV-2, it’s crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-positive (n = 219,264), and COVID-negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
Socio-economic disparities and predictors of fertility among adolescents aged 15 to 19 in Zambia: Evidence from the Zambia demographic and health survey (2018)
Authors: Shumba Samson , Moonga Vanessa , Miyoba Thomas O. , Jere Stephen , Nkonde Jessy M. , Mumba Peter
Published: December 2023

Background

Annually, 12 million girls aged 15-19 give birth globally, with Africa hosting 19% of the youth aged 15-24. Zambia sees 29% of adolescents experiencing childbirth, with notable variations among age groups. Predictors of adolescent fertility include age, residential area, education, contraceptive use, and socioeconomic status. Studies emphasize increased health risks for adolescent mothers, including eclampsia and systemic infections, while infants face elevated risks such as low birth weight and severe neonatal conditions. Projections anticipate a continued rise in these trends by 2030.

Method

The analysis utilized the 2018 Zambia Demographic Health Survey (ZDHS). The association between dependent and independent variables was assessed using the Rao–Scott Chi-square test. Determinants of adolescent fertility were identified through a multilevel ordinal logistic regression conducted at a significance level of 5%. Graphs were generated using Excel, and the analysis was carried out using Stata version 14.2.

Results

A total of 3,112 adolescents were involved in the study, revealing that 75.88% had not given birth, 21.14% had one child, and 2.98% had at least two children. The findings revealed that education played a protective role, with adjusted odds ratios (AOR) of 0.47 (95% CI, 0.23 – 0.97), 0.21 (95% CI, 0.10 – 0.47), and 0.03 (95% CI, 0.00 – 0.54) for primary, secondary, and tertiary education, respectively. On the other hand, certain factors were associated with an elevated risk of fertility. These included the age of adolescents, educational attainment, marital status, wealth index, contraceptive use, exposure to family planning (FP) messages, being educated about FP at health facilities, and age at first sexual encounter. Among contextual factors, only community age at first birth was identified as a predictor of fertility, AOR, 1.59 (95% CI, 1.01 – 2.52).

Conclusion

The study highlights sociodemographic disparities in adolescent fertility, emphasizing the need for targeted sexual reproductive health policies. Education protects against having more than one child, while marital status significantly influences fertility, particularly for married adolescents. The research provides valuable insights into the complex factors shaping adolescent fertility in Zambia, offering guidance for interventions and policies to support this vulnerable demographic.
Improved coherence measure for EEG-based speech tracking in hearing impaired listeners
Authors: Keding Oskar , Alickovic Emina , Skoglund Martin , Sandsten Maria
Published: December 2023

In the literature, auditory attention is explored through neural speech tracking, primarily entailing modeling and analyzing electroencephalography (EEG) responses to natural speech via linear filtering. Our study takes a novel approach, introducing an enhanced coherence estimation technique that employs multitapers to assess the strength of neural speech tracking. This enables effective discrimination between attended and ignored speech. To mitigate the impact of colored noise in EEG, we address two biases – overall coherence-level bias and spectral peak-shifting bias. In a listening study involving 32 participants with hearing impairment, tasked with attending to competing talkers in background noise, our coherence-based method effectively discerns EEG representations of attended and ignored speech. We comprehensively analyze frequency bands, individual frequencies, and EEG channels. Frequency bands of importance are shown to be delta, theta and alpha, as well as the central EEG channels. Lastly, we showcase coherence differences across different noise reduction settings implemented in hearing aids, underscoring our method’s potential to objectively assess auditory attention and enhance hearing aid efficacy.
Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion
Authors: Polsani Nikaya , Yung Theodora , Thomas Evan , Phung-Rojas Melissa , Gupta Isha , Denker Julie , Feng Xiaotian , Ibarra Beatriz , Hopyan Sevan , Atit Radhika P.
Published: December 2023

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral for calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. During apical expansion, we found that mouse calvarial primordia have consistent cellular proliferation, density, and survival with complex tissue scale deformations, raising the possibility that morphogenetic movements underlie expansion. Time lapse light sheet imaging of mouse embryos revealed that calvarial progenitors intercalate in 3D to converge supraorbital arch mesenchyme mediolaterally and extend it apically. In contrast, progenitors located further apically exhibited protrusive and crawling activity. CM cells express non-canonical Wnt/Planar Cell Polarity (PCP) core components and calvarial osteoblasts are bidirectionally polarized. We found non-canonical ligand,Wnt5a-/-mutants have less dynamic cell rearrangements, protrusive activity, and a flattened head shape. Loss of cranial mesenchyme-restrictedWntless (CM-Wls),a gene required for secretion of all Wnt ligands, led to diminished apical expansion of OSX+calvarial osteoblasts in the frontal bone primordia in a non-cell autonomous manner without perturbing proliferation or survival. Calvarial osteoblast polarization, progressive cell elongation and enrichment for actin cytoskeleton protein along the baso-apical axis were dependent on CM-Wnts. Thus, CM-Wnts regulate cellular behaviors during calvarial morphogenesis and provide tissue level cues for efficient apical expansion of calvarial osteoblasts. These findings also offer potential insights into the etiologies of calvarial dysplasias.
Similarity score for screening phase-retrieved maps in X-ray diffraction imaging – characterization in reciprocal space
Authors: Takayama Yuki , Nakasako Masayoshi
Published: December 2023

X-ray diffraction imaging (XDI) is utilized for visualizing the structures of non-crystalline particles in material sciences and biology. In the structural analysis, phase-retrieval (PR) algorithms are applied to the diffraction amplitude data alone to reconstruct the electron density map of a specimen particle projected along the direction of the incident X-rays. However, PR calculations may not lead to good convergence because of a lack of diffraction patterns in small-angle regions and Poisson noise in X-ray detection. Therefore, the PR calculation is still a bottleneck for the efficient application of XDI in the structural analyses of non-crystalline particles. For screening maps from hundreds of trial PR calculations, we have been using a score and measuring the similarity between a pair of retrieved maps. Empirically, probable maps approximating the particle structures gave a score smaller than a threshold value, but the reasons for the effectiveness of the score are still unclear. In this study, the score is characterized in terms of the phase differences between the structure factors of the retrieved maps, the usefulness of the score in screening the maps retrieved from experimental diffraction patterns is demonstrated, and the effective resolution of similarity-score-selected maps is discussed.
Crystal structures of three uranyl–acetate–bipyridine complexes crystallized from hydraulic fracking fluid
Authors: Whittington Abigail A. , Keimowitz Alison R. , Tanski Joseph M.
Published: December 2023

Hydraulic fracking exposes shale plays to acidic hydraulic fracking fluid (HFF), releasing toxic uranium (U) along with the desired oil and gas. With no existing methods to ensure U remains sequestered in the shale, this study sought to add organic ligands to HFF to explore potential U retention in shale plays. To test this possibility, incubations were set up in which uranyl acetate and one organic bipyridine ligand (either 2,2′-, 2,3′-, 2,4′-, or 4,4′-bipyridine) were added to pristine HFF as the crystallization medium. After several months and complete evaporation of all volatiles, bulk yellow crystalline material was obtained from the incubations, three of which yielded crystals suitable for single-crystal analysis, resulting in two novel structures and a high-quality structure of a previously described compound. The UO2
VI acetate complexes bis(acetato-κ2
O,O′)(2,2′-bipyridine-κ2
N,N′)dioxidouranium(VI), [U(C2H3O2)2O2(C10H8N2)2] or [2,2′-bipyridine]UVIO2(CH3CO2)2, (I), and bis(acetato-κ2
O,O′)(2,4′-bipyridine-κN
1′)dioxidouranium(VI), [U(C2H3O2)2O2(C10H8N2)2] or [2,4′-bipyridine]2UVIO2(CH3CO2)2, (III), contain eight-coordinate UVI in a pseudo-hexagonal bipyramidal coordination geometry and are molecular, packing via weak C—H...O/N interactions, whereas catena-poly[bis(2,3′-bipyridinium) [di-μ-acetato-μ3-hydroxido-μ-hydroxido-di-μ3-oxido-hexaoxidotriuranium(VI)]–2,3′-bipyridine–water (1/1/1)], (C10H9N2)2[U3(C2H3O2)2O8(OH)2]·C10H8N2·H2O or {[2,3′-bipyridinium]2[2,3′-bipyridine][(UVIO2)3(O)2(OH)2(CH3CO2)2·H2O]}
n
, (II), forms an ionic one-dimensional polymer with seven-coordinate pentagonal bipyramidal UVI centers and hydrogen-bonding interactions within each chain. The formation of these crystals could indicate the potential for bipyridine to bind with U in shale during fracking, which will be explored in a future study via ICP-MS (inductively coupled plasma mass spectrometry) analyses of U concentration in HFF/bipyridine/shale incubations. The variation seen here between the molecular structures may indicate variance in the ability of bipyridine isomers to form complexes with U, which could impact their ability to retain U within shale in the context of fracking.
Optimal capital structure with supplier market power
Authors: Cui Xue , Sarkar Sudipto , Zhang Chuanqian
Published: December 2023

We use a real‐option model to study the effect of input supplier's market power on a firm's capital structure, and identify the Nash equilibrium outcome (firm's investment and financing policies and its supplier's pricing policy). When its supplier has market power, the firm will reduce leverage ratio and delay investment. This can help explain why observed leverage ratios are lower than in traditional capital‐structure models (without supplier market power). Firm value can be increased by the vertical acquisition of the supplier, which would also result in a higher leverage ratio. This helps explain the observed increase in leverage ratios after acquisitions.
Corporate transparency among government suppliers: Implications for firm valuation
Authors: Esqueda Omar A. , Ngo Thanh N.
Published: December 2023

Corporate transparency has a positive impact on firm valuation, as predicted by agency theory; however, the transparency of strategically important government suppliers is not rewarded with higher valuations as the market expects politically sensitive firms to be inherently more transparent. The association between transparency and valuation among politically sensitive firms is consistent with the political cost hypothesis. We address endogeneity concerns using propensity score matching, Heckman's self‐selection models and entropy balancing. Our findings offer novel insights, suggesting that the influence of transparency on corporate valuation varies with political sensitivity – a significant consideration for both finance professionals and scholars.
Debate and Decide: Innovative Participatory Governance in South Australia 2010–2018
Authors: Ryan Matt D.
Published: December 2023

This article provides an account of how innovative participatory governance unfolded in South Australia between 2010 and 2018. In doing so it explores how an ‘interactive’ political leadership style, which scholarship argues is needed in contemporary democracy, played out in practice. Under the leadership of Premier Jay Weatherill this approach to governing, known as ‘debate and decide’, became regarded as one of the most successful examples of democratic innovation globally. Using an archival and media method of analysis the article finds evidence of the successful application of an interactive political leadership style, but one that was so woven into competitive politics that it was abandoned after a change in government in March 2018. To help sustain interactive political leadership styles the article argues for research into how a broader base of politicians perceives the benefits and risks of innovative participatory governance. It also argues for a focus on developing politicians' collaborative leadership capabilities. However, the article concludes by asking: if political competition is built into our system of government, are we be better off leveraging it, rather than resisting it, in the pursuit of democratic reform?
let‐7g sensitized liver cancer cells to 5‐fluorouracil by downregulating ABCC10 expression
Authors: Chen Yun , Zhang Bocheng , Zhong Cui , Zhou Yuqing , Xue Lei , Luo Chenhui , Yi Liang , Gong Qian , Long Ying
Published: December 2023

Patients with advanced liver cancer may benefit from 5‐fluorouracil (5‐FU) therapy. However, most of them eventually faced drug resistance, resulting in a poor prognosis. The present study aims to explore the potential mechanism of let‐7g/ABCC10 axis in the regulation of 5‐FU resistance in liver cancer cells. Huh‐7 cells were used to construct 5‐FU resistant Huh‐7/4X cells. CCK8, flow cytometry, and TUNEL staining were used to detect the characterization of Huh‐7 cells and Huh‐7/4X cells. Double luciferase report, PCR, and western blot analyses were used to detect the regulatory effects between let‐7g and ABCC10. The levels of biomarkers related to cell cycle progression and apoptosis were detected by western blot assays. The role of let‐7g in 5‐FU sensitivity of liver cancer cells was evaluated in nude mice. Compared with LX‐2 cells, the expression of let‐7g was decreased in Hep3B, HepG2, Huh‐7, and SK‐Hep1 cells, with the lowest expression in Huh‐7 cells. The sensitivity of Huh‐7 cell to 5‐FU was positively correlated with let‐7g expression. Transfection of let‐7g mimics inhibited the viability of Huh‐7/4X cells by prolonging the G1 phase, with the downregulation of ABCC10, PCNA, Cyclin D1, and CDK4. Meanwhile, let‐7g promoted apoptosis to increase 5‐FU sensitivity of Huh‐7/4X by downregulating ABCC10, Bcl‐XL as well as upregulating Bax, C‐caspase 3, and C‐PARP. Dual‐luciferase assay further confirmed that let‐7g inhibited ABCC10 expression by binding to the ABCC10 3’‐UTR region. Furthermore, let‐7g increased the sensitivity of Huh‐7/4X to 5‐FU in vitro and in vivo, which can be reversed by ABCC10 overexpression. In conclusion, let‐7g sensitized liver cancer cells to 5‐FU by downregulating ABCC10 expression.
A Perceptual Shape Loss for Monocular 3D Face Reconstruction
Authors: Otto C. , Chandran P. , Zoss G. , Gross M. , Gotardo P. , Bradley D.
Published: December 2023

Monocular 3D face reconstruction is a wide‐spread topic, and existing approaches tackle the problem either through fast neural network inference or offline iterative reconstruction of face geometry. In either case carefully‐designed energy functions are minimized, commonly including loss terms like a photometric loss, a landmark reprojection loss, and others. In this work we propose a new loss function for monocular face capture, inspired by how humans would perceive the quality of a 3D face reconstruction given a particular image. It is widely known that shading provides a strong indicator for 3D shape in the human visual system. As such, our new ‘perceptual’ shape loss aims to judge the quality of a 3D face estimate using only shading cues. Our loss is implemented as a discriminator‐style neural network that takes an input face image and a shaded render of the geometry estimate, and then predicts a score that perceptually evaluates how well the shaded render matches the given image. This ‘critic’ network operates on the RGB image and geometry render alone, without requiring an estimate of the albedo or illumination in the scene. Furthermore, our loss operates entirely in image space and is thus agnostic to mesh topology. We show how our new perceptual shape loss can be combined with traditional energy terms for monocular 3D face optimization and deep neural network regression, improving upon current state‐of‐the‐art results.
Introduction: Perceiving and conceiving the Asian city1
Authors: Holwitt Pablo
Published: December 2023

Asian cities are the setting of a vast agglomeration of transportation devices and services. These means of transport are inseparable from distinct concepts and images of the city. Interventions into modes of urban transport are inspired by visions for the future of urban life and quotidian practices of traversing urban space foster particular experiences that produce distinct ideas about the city. This special issue takes the multiplicity of mobility practices in Asian cities as a point of departure to interrogate connections between embodied experiences and collective representations. Drawing on three bodies of literature that deal with the topics of urban imaginaries, infrastructures as well as the body and the city, this introduction provides a theoretical framework for the study of connections between perception and conception of cities that informs the contributions to this special issue. It sets the stage for a set of three interconnected questions that guide the contributions: How do people affectively engage with urban spaces through practices of bodily movement? How are these practices of movement related to and generative of specific ideas and representations of the city? How do these practices of movement transform, challenge, subvert, or conform to dominant ideas and representations of the city?
The becoming of worker mothers: The untold narratives of an identity transition
Authors: Garcia‐Lorenzo Lucia , Carrasco Lorena , Ahmed Zehra , Morgan Alice , Sznajder Kim , Eggert Leonie
Published: December 2023

Worker mothers still struggle to find a good balance between their care and work identities. Most research on motherhood at work focuses on how organizational structures can enable professional women to find a balance between caring and work identities neglecting their personal experiences and how they understand themselves in relation to both motherhood and work. We propose to use a liminal identity work perspective to explore the identity tensions that professional women experience during their transition into motherhood and how they manage it. To explore this question, we conducted a qualitative study over 2 years with worker mothers in Latin and North America, Europe, Asia Pacific, and Africa. The thematic and narrative analysis of 80 individual narrative interviews shows the emergence of two coexisting identity narratives. The first narrative understands motherhood as a linear process, where women experience liminality, uncertainty, and identity loss but eventually return to work after having aggregated their new worker mother identities during maternity leaves. The second coexisting narrative challenges this linear and finite view by highlighting the transition to motherhood as a continuous, liminoid, and never‐ending process. The two narratives are contextualized and managed differently according to the different cultural, historical, and social contexts where they are developed; the overall results present motherhood as a ‘liminoid’ experience that requires constant identity work to navigate the tensions emerging between potentially new and customary identities and behaviors in work contexts.
Disruption of a kasB homolog gene (kasB) causes attenuation of cell invasion and virulence of Nocardia seriolae
Authors: Zhou Su‐Ming , Shu Feng‐Ling , Liu Hao , Qian Dong , Xie Jia‐Song , Wang Ya‐Jun , Yin Fei
Published: December 2023

Nocardia seriolae is the primary aetiological agent of nocardiosis in fish, which causes mass mortality in freshwater and marine fish. β‐ketoacyl‐ACP synthase (KAS) is one of the essential enzymes in the synthesis of mycolic acids (MASs) in Mycobacterium spp. and has been chosen as the target for therapeutic intervention in mycobacterial diseases. In the present study, a kasB homologue gene (kasB) was identified in the genome of N. seriolae, and the gene‐deficient mutant (ΔkasB) was generated based on a clinical isolate, XSYC‐Ns. Compared to the wild‐type (WT) strain, the ΔkasB showed a measurably growth defect in vitro but retained the acid‐fastness in acid‐fast staining. Observation of the cell ultrastructure showed some alterations in the cell wall of the ΔkasB strain. Compared to its original strain, the cell wall lipid layer seemed sparser, and a wider electron‐transparent zone was observed in the cell wall of ΔkasB strain. Moreover, the ΔkasB strain showed impaired ability of cell invasion as well as intracellular survival in the cell line originating from the head‐kidney of the large yellow croaker (LYC‐hK), compared to its original strain. In addition, the deficiency of ΔkasB significantly attenuated the virulence of N. seriolae in largemouth bass. The present study suggested that the ΔkasB gene might be involved in the synthesis of extracellular cell‐wall lipids in N. seriolae and play a crucial role in its pathogenicity.
Randomized controlled trial of effects of a familiarization video and patient‐controlled Entonox inhalation on patient stress levels and clinical efficacy of flexible sigmoidoscopy without analgesia or sedation for investigation of fresh rectal bleeding
Authors: Bagshaw Philip , Cameron Christopher , Aramowicz Jaana , Frampton Christopher , Pretty Christopher
Published: December 2023

Background and Aim

Flexible sigmoidoscopy (FS) without analgesia or sedation can be unpleasant for patients, resulting in unsatisfactory examinations. Prior familiarization videos (FVs) and intra‐procedural Entonox inhalation have shown inconsistent effects. This study investigated their effects on undesirable participant factors (anxiety, stress, discomfort, pain, satisfaction, later unpleasant recall of procedure, and vasovagal reactions) and clinical effectiveness (extent of bowel seen, lesions detected, and procedural/recovery times).

Methods

This cluster‐randomized single‐center study evaluated 138 participants undergoing FS. There were 46 controls, 49 given access to FV, and 43 access to both FV and self‐administered Entonox. Participant factors were measured by self‐administered questionnaires, independent nurse assessments, and heart rate variability (HRV) metrics.

Results

Questionnaires showed that the FV group was slightly more tense and upset before FS, but knowledge of Entonox availability reduced anxiety. Nonlinear HRV metrics confirmed reduced intra‐procedural stress response in the FV/Entonox group compared with controls and FV alone (P < 0.05). Entonox availability allowed more bowel to be examined (P < 0.001) but increased procedure time (P < 0.05), while FV alone had no effect. FV/Entonox participants reported 1 month after FS less discomfort during the procedure. Other comparisons showed no significant differences between treatment groups, although one HRV metric showed some potential to predict vasovagal reactions.

Conclusions

Entonox availability significantly improved clinical effectiveness and caused a slight reduction in undesirable participant factors. The FV alone did not reduce undesirable participant factors or improve clinical effectiveness. Nonlinear HRV metrics recorded effects in agreement with stress reduction and may be useful for prediction of vasovagal events in future studies.
Complete holography‐based system for the identification of microparticles in water samples
Authors: Júnior Andouglas Gonçalves da Silva , Distante Cosimo , Gonçalves Luiz Marcos Garcia
Published: December 2023

Here, we present a comprehensive holography‐based system designed for detecting microparticles through microscopic holographic projections of water samples. This system is designed for researchers who may be unfamiliar with holographic technology but are engaged in microparticle research, particularly in the field of water analysis. Additionally, our innovative system can be deployed for environmental monitoring as a component of an autonomous sailboat robot. Our system's primary application is for large‐scale classification of diverse microplastics that are prevalent in water bodies worldwide. This paper provides a step‐by‐step guide for constructing our system and outlines its entire processing pipeline, including hologram acquisition for image reconstruction.
Competition from informal firms and new‐to‐market product innovation: A competitive rivalry framework
Authors: Wang Kui , Wang Tao
Published: December 2023

Although informal firms are rare in developed economies, they are prevalent in emerging economies and create significant competitive pressure for formal firms. Recent literature has focused on the effects of informal competition on product innovation, but the results have been inconsistent. This discordance motivated this study. Drawing on insights from competitive rivalry, this study investigates how informal competition affects formal firms’ product innovativeness (i.e., whether to develop new‐to‐market products or not). Using a sample of firms operating in Eastern Europe and Central Asia from the World Bank Enterprise Survey, we find that if formal firms encounter intense competitive pressure from informal firms, they are less inclined to develop new‐to‐market products. Furthermore, credit constraints strengthen the adverse effect of competitive pressure from informal firms on the development of new‐to‐market product innovation, but state legitimacy weakens this effect. This investigation provides insight into the barriers to innovation in emerging economies and adds to the existing literature by highlighting the need to consider the varied effects of informal competition on different types of product innovation.
Prediction of viscoelastic properties of peanut‐based 3D printable food ink
Authors: Kadival Amaresh , Mitra Jayeeta , Kaushal Manish , Machavaram Rajendra
Published: December 2023

Viscoelastic properties of 3D printable peanut‐based food ink were investigated using frequency sweep and relaxation test. The incorporation of xanthan gum (XG) improved the shear thinning behavior (n value ranging from 0.139 to 0.261) and lowered the η*, G′, and G′′ values, thus making food ink 3D printable. The addition of XG also caused a downward shift in the relaxation curve. This study evaluates the possibility of an artificial neural network (ANN) approach as a substitute for the Maxwell three‐element and Peleg model for predicting the viscoelastic behavior of food ink. The results revealed that all three models accurately predicted the decay forces. The inclusion of XG decreased the hardness and enhanced the cohesiveness, so enabling the 3D printing of food ink. The hardness was highly positively correlated with Maxwell model parameters Fe, F1, F2, F3, and Peleg constant k2 (0.57) and negatively correlated with k1 (−0.76).
Monetary policy, inflation and distributional impact: South Africa's case
Authors: Miyajima Ken
Published: December 2023

This paper presents further empirical support for the finding that the impact of inflation and that of policy instruments to manage inflation are not distributed equally across households of different income groups. In particular, the evidence using South African data suggests that monetary policy tightening, which seeks to maintain low and stable inflation, has a relatively modest effect on real consumption of poorer households, who tend to rely on government grants and spend larger shares of income on food stuff, while the reduction in real consumption of wealthier households is much larger. This may be due to the fact that low and stable inflation help maintain the value of government grants and cap food prices both in real terms, and higher interest rates reduce labour income, weaken asset price performance and increase debt service cost.
Back Matter
Authors: Onder E. Nihan
Published: December 2023

This back matter contains the References.
Nuclear Power Reactors and Their Fuels
Authors: Onder E. Nihan
Published: December 2023

Ceramic oxide fuels, in particular, uranium dioxide (UO2) in the form cylindrical pellets, with zircaloy as cladding are used in the majority of operating nuclear power reactors. However, some reactors employ mixed uranium-plutonium oxide (mixed oxide, MOX2; (U,Pu)O2±x). The two major isotopes of natural uranium are 235U (0.711 wt%) and 238U 99.284 wt% with traces of 234U isotope. In the light water-cooled reactors (LWR), including pressurized water (PWR), boiling water (BWR) and water-cooled and water-moderated (VVER) power reactors, the fuel is enriched to increase the abundance of fissile 235U in the naturally occurring uranium up to slightly less than 5 wt% because the main contributor to fissioning is 235U. In the pressurized heavy3 water reactors (PHWR), excluding the fuel used in the German pressurized vessel design in Atucha in Argentina, natural uranium is used in fabricating the UO2 pellets. Due to its lower neutron absorption, heavy water (D2O) is one of the most efficient moderators to be used with natural uranium. For LWR applications, fuel needs to be enriched (up to 4.9 wt% 235U in U) because light water (H2O) not only scatters but absorbs many neutrons to be an effective moderator to be used with natural uranium.
Fissioning, Heat Generation and Transfer, and Burnup
Authors: Onder E. Nihan
Published: December 2023

Energy is liberated by an exothermic reaction in the fission process due to differences in the nuclear binding energy between the incoming (i.e., neutron and uranium) and outgoing (fission products, neutrons, etc.) products of the nuclear transmutation, when a heavy nucleus, like uranium, splits into lighter nuclei. In a nuclear reactor that uses UO2 as a fuel, the main source of energy is the radioactive nuclide 235U: 235U reacts with a neutron to generate 236U (in excited state). Then, 236U splits into lighter two (e.g., 92Kr and 141Ba) or more nuclei and also produces additional neutrons, creating a chain reaction: the newly formed neutrons react with more 235U to form 236U that undergoes fission. This process repeats itself over and over again, in a controlled manner, meaning that the number of neutrons6 in the process is kept constant to maintain a steady state power generation. The energy from fission is used to generate electricity by powering a turbine.
Fuel Pellet, Element and Assembly
Authors: Onder E. Nihan
Published: December 2023

Fuels that are fabricated for water-cooled power reactors are based on ceramic uranium dioxide (UO2), sintered from the powder to form fuel pellets. Fuel pellets, usually about 10 mm to 12 mm in diameter and 10 to 15 mm in length, are stacked in zirconium alloy (i.e., zircaloy) tubes, forming fuel elements. Numerous fuel elements form a fuel assembly. Note that assembly is the term used for LWR fuel and bundle is the term used for pressure-tube PHWR; however, assembly is used here in general terms. The specifications of pellets, fuel elements and assemblies are discussed next.
Can the global marine aquarium trade (MAT) be a model for sustainable coral reef fisheries?
Authors: Watson Gordon J. , Kohler Shanelle , Collins Jacob-Joe , Richir Jonathan , Arduini Daniele , Calabrese Claudio , Schaefer Martin
Published: December 2023

Globally, 6 million coral reef fishers provide ~25% of emergent countries’ catch, but species have low value. The marine aquarium trade (MAT) targets high-value biodiversity, but missing data amplify draconian governance and demand for international prohibition. To stimulate sustainability and reef conservation investment, we generate a fiscal baseline using the first global analysis of numbers, diversity, and biomass of MAT-traded organisms. Each year, ~55 million organisms worth US$2.15 billion at retail are traded comparable with major fisheries, e.g., tuna. A sustainable MAT also requires overexploitation assessments. We identify 25 species/genera with “Extremely High” risk ratios and place the Indonesian and Sulu-Celebes Seas in the highest exploitation category. Despite predicted hobbyist number increases, unabated reef degradation and low governance will transform the MAT into an aquaculture-dominated industry decoupled from communities (i.e., culture located in importing countries). A “MAT-positive” future requires evidence-based management/governance, consumer education, and sustainable practice incentivization but can address the biodiversity and social and economic inequality crises.
Twenty natural amino acid substitution screening at the last residue 121 of influenza A virus NS2 protein reveals the critical role of NS2 in promoting virus genome replication by coordinating with viral polymerase
Authors: Zhang Lei , Shao Yuekun , Wang Yingying , Yang Qiuxian , Guo Jiamei , Gao George F. , Deng Tao
Published: December 2023

Both influenza A virus genome transcription (vRNA→mRNA) and replication (vRNA→cRNA→vRNA), catalyzed by the influenza RNA polymerase (FluPol), are dynamically regulated across the virus life cycle. It has been reported that the last amino acid I
121
of the viral NS2 protein plays a critical role in promoting viral genome replication in influenza mini-replicon systems. Here, we performed a 20 natural amino acid substitution screening at residue NS2-I
121
in the context of virus infection. We found that the hydrophobicity of the residue 121 is essential for virus survival. Interestingly, through serial passage of the rescued mutant viruses, we further identified adaptive mutations PA-K19E and PB1-S713N on FluPol which could effectively compensate for the replication-promoting defect caused by NS2-I
121
mutation in the both mini-replicon and virus infection systems. Structural analysis of different functional states of FluPol indicates that PA-K19E and PB1-S713N could stabilize the replicase conformation of FluPol. By using a cell-based NanoBiT complementary reporter assay, we further demonstrate that both wild-type NS2 and PA-K19E/PB1-S713N could enhance FluPol dimerization, which is necessary for genome replication. These results reveal the critical role NS2 plays in promoting viral genome replication by coordinating with FluPol.

IMPORTANCE

The intrinsic mechanisms of influenza RNA polymerase (FluPol) in catalyzing viral genome transcription and replication have been largely resolved. However, the mechanisms of how transcription and replication are dynamically regulated remain elusive. We recently reported that the last amino acid of the viral NS2 protein plays a critical role in promoting viral genome replication in an influenza mini-replicon system. Here, we conducted a 20 amino acid substitution screening at the last residue 121 in virus rescue and serial passage. Our results demonstrate that the replication-promoting function of NS2 is important for virus survival and efficient multiplication. We further show evidence that NS2 and NS2-I
121
adaptive mutations PA-K19E/PB1-S713N regulate virus genome replication by promoting FluPol dimerization. This work highlights the coordination between NS2 and FluPol in fulfilling efficient genome replication. It further advances our understanding of the regulation of viral RNA synthesis for influenza A virus.
EFHD2 cooperates with E3 ubiquitin ligase Smurf1 to facilitate virus infection by promoting the degradation of TRAF6 in teleost fish
Authors: Wang Pengfei , Li Ye , Sun Yuena , Xu Tianjun
Published: December 2023

The ubiquitin-proteasome system is one of the most important protein stability regulation systems. It can precisely regulate host immune responses by targeting signaling proteins. TRAF6 is a crucial E3 ubiquitin ligase in host antiviral signaling pathway. Here, we discovered that EF-hand domain-containing protein D2 (EFHD2) collaborated with the E3 ubiquitin ligase Smurf1 to potentiate the degradation of TRAF6, hence facilitating RNA virus
Siniperca chuatsi
rhabdovirus infection. The mechanism analysis revealed that EFHD2 interacted with Smurf1 and enhanced its protein stability by impairing K48-linked polyubiquitination of Smurf1, thereby promoting Smurf1-catalyzed degradation of TRAF6. This study initially demonstrated a novel mechanism by which viruses utilize host EFHD2 to achieve immune escape and provided a new perspective on the exploration of mammalian innate immunity.

IMPORTANCE

Viruses induce host cells to activate several antiviral signaling pathways. TNF receptor-associated factor 6 (TRAF6) plays an essential role in these pathways. Numerous studies have been done on the mechanisms of TRAF6-mediated resistance to viral invasion. However, little is known about the strategies that viruses employ to antagonize TRAF6-mediated antiviral signaling pathway. Here, we discovered that EFHD2 functions as a host factor to promote viral replication. Mechanistically, EFHD2 potentiates Smurf1 to catalyze the ubiquitin-proteasomal degradation of TRAF6 by promoting the deubiquitination and stability of Smurf1, which in turn inhibits the production of proinflammatory cytokines and interferons. Our study also provides a new perspective on mammalian resistance to viral invasion.
Host factor MxA restricts Dabie bandavirus infection by targeting the viral NP protein to inhibit NP-RdRp interaction and ribonucleoprotein activity
Authors: Chang Meng , Min Yuan-Qin , Xu Zhao , Deng Fei , Wang Hualin , Ning Yun-Jia
Published: December 2023

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case mortality rates, which is caused by Dabie bandavirus (DBV), a novel pathogen also termed as SFTS virus (SFTSV). Currently, no specific therapeutic drugs or vaccines are available for SFTS. Myxovirus resistance protein A (MxA) has been shown to inhibit multiple viral pathogens; however, the role of MxA in DBV infection is unknown. Here, we demonstrated that DBV stimulates MxA expression which, in turn, restricts DBV infection. Mechanistic target analysis revealed that MxA specifically interacts with the viral nucleocapsid protein (NP) in a manner independent of RNA. Minigenome reporter assay showed that in agreement with its targeting of NP, MxA inhibits DBV ribonucleoprotein (RNP) activity. In detail, MxA interacts with the NP N-terminal and disrupts the interaction of NP with the viral RNA-dependent RNA polymerase (RdRp) but not NP multimerization, the critical activities of NP for RNP formation and function. Furthermore, MxA N-terminal domain was identified as the functional domain inhibiting DBV infection, and, consistently, then was shown to interact with NP and obstruct the NP-RdRp interaction. Additionally, threonine 103 within the N-terminal domain is important for MxA inhibition to DBV, and its mutation (T103A) attenuates MxA binding to NP and obstruction of the NP-RdRp interaction. This study uncovers MxA inhibition of DBV with a series of functional and mechanistical analyses, providing insights into the virus−host interactions and probably helping inform the development of antiviral agents in the future.

IMPORTANCE

DBV/SFTSV is an emerging high-pathogenic virus. Since its first identification in China in 2009, cases of DBV infection have been reported in many other countries, posing a significant threat to public health. Uncovering the mechanisms of DBV-host interactions is necessary to understand the viral pathogenesis and host response and may advance the development of antiviral therapeutics. Here, we found that host factor MxA whose expression is induced by DBV restricts the virus infection. Mechanistically, MxA specifically interacts with the viral NP and blocks the NP-RdRp interaction, inhibiting the viral RNP activity. Further studies identified the key domain and amino acid residue required for MxA inhibition to DBV. Consistently, they were then shown to be important for MxA targeting of NP and obstruction of the NP-RdRp association. These findings unravel the restrictive role of MxA in DBV infection and the underlying mechanism, expanding our knowledge of the virus-host interactions.