bluuebunny/crossref_metadata_2025 huggingface dataset:
Rewilding alters mouse epigenetic aging
Authors: Zipple Matthew N , Zhao Ivan , Kuo Daniel Chang , Lee Sol Moe , Sheehan Michael J , Zhou Wanding
Published: September 2024

The aging of mammalian epigenomes fundamentally alters cellular functions, and such changes are the focus of many healthspan and lifespan studies. However, studies of this process typically use mouse models living under standardized laboratory conditions and neglect the impact of variation in social, physical, microbial, and other aspects of the living environment on age-related changes. We examined differences in age-associated methylation changes between traditionally lab-reared and “rewilded” C57BL6/J mice, which lived in an outdoor field environment with enhanced ecological realism. Systematic analysis of age-associated methylation dynamics in the liver indicates a genomic region-conditioned, faster epigenetic aging rate in mice living in the field than those living in the lab, implicating perturbed 3D genome conformation and liver function. Altered epigenetic aging rates were more pronounced in sites that gain methylation with age, including sites enriched for transcription factor binding related to DNA repair. These observations underscore the overlooked role of the social and physical environment in epigenetic aging with implications for both basic and applied aging research.
A genetically encoded fluorescent sensor enables sensitive and specific detection of IDH mutant associated oncometabolite D-2-hydroxyglutarate
Authors: Choate Kristian A. , Konickson Wren W.L. , Jennings Matthew J. , Mann Paul B. , Winn Robert J. , Kamson David O. , Pratt Evan P.S.
Published: September 2024

D-2-hydroxyglutarate (D-2-HG) is an oncometabolite that accumulates due to mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2). D-2-HG may be used as a surrogate marker forIDH1/2mutant cancers, yet simple and specific methods for D-2-HG detection are limited. Here, we present the development and characterization of a genetically encoded fluorescent sensor of D-2-HG (D2HGlo). D2HGlo responds to clinically relevant concentrations of D-2-HG, demonstrates exceptional selectivity and can quantify D-2-HG in various body fluids and glioma tumor supernatants. Additionally, analysis of tumor lysates using D2HGlo accurately predicted the IDH mutational status of gliomas. Collectively, these results suggest that D2HGlo may be anin vitrodiagnostic device for the detection and monitoring of IDH mutant cancers through liquid biopsies. In addition to D2HGlo’s clinical utility, we also present preliminary findings for its adaptation to the cellular environment. To assess D-2-HG production in living immortalized glioma cells, we engineered D2HGlo sensors that localize to subcellular compartments, which yielded findings of elevated D-2-HG in the cytosol, mitochondria, and nucleus ofIDH1mutant cells.
Development of multi-species qPCR assays for a stress transcriptional profiling (STP) Chip to assess the resilience of salmonids to changing environments
Authors: Islam Shahinur S. , Heath Daniel D. , Dixon Brian , Karpowicz Phillip , Vuu Kelvin , LeBlanc Jonathon , Bernier Nicholas J. , Jeffries Kenneth M.
Published: September 2024

Ecologically and socio-economically important salmonid fishes in Canada are threatened by diverse environmental stressors. However, predicting species’ responses to environmental change requires understanding the underlying molecular mechanisms governing environmental stress tolerance. Developing advanced molecular genetic tools will provide opportunities to predict how salmonid fishes will respond to environmental stressors and assess their adaptive potential and vulnerability into the future. Here, we developed a panel of Taqman quantitative PCR (qPCR) assays designed to measure mRNA transcript abundance at selected candidate loci for use across salmonids. We designed and applied those assays for use in a high-throughput nanofluidic OpenArray Stress Transcriptional Profiling Chip (STP-Chip) capable of 2688 simultaneous qPCR at multiple gene loci (112 targets for 12 samples in duplicate). Using the nanofluidic STP-Chip, we tested these 112 multi-species qPCR assays using gill, liver and muscle tissue from eight species of salmonids across four genera. Of the selected 112 assays, 69 assays showed amplification in gill, 64 in liver, and 67 in muscle across all eight salmonid species. The percentage of assays that showed amplification across three tissues varied between genera: In general,Salmo,Oncorhynchus, andSalvelinusspecies showed a higher success rate thanCoregonusspecies. Stress, circadian rhythm, apoptosis, growth-metabolism, and detoxification-relevant assays showed high success rates for amplification across all salmonid species for all three tissues. In contrast, neural plasticity, appetite regulation, osmoregulation, immune function, endocrine disruption, and hypoxia-relevant assays showed low success. Not surprisingly, we observed tissue-specific variation among qPCR amplification patterns. There were significant differences in mRNA transcript abundance among species across the four genera, but we did not see variation between species from the same genus. These qPCR assays can be used to design custom STP-Chips that can be used for quantifying stress in salmonid fish, improving health through more accurate diagnostic tests for disease, and monitoring adaptation to accelerated climate change regionally and globally.
Different signaling interpretations by PKC eta and theta control T cell function and exhaustion
Authors: Mann Thomas H. , Knox Hannah M. , Ma Shixin , Furgiuele Jesse , Globig Anna-Maria , LaPorta Michael , Chung Hokyung K. , McDonald Bryan , Ghassemian Majid , Zhao Steven , Tseng Hubert , Farsakoglu Yagmur , Tripple Victoria , Koo Johnny , Newton Alexandra C. , Kaech Susan M.
Published: September 2024

Chronic antigen signaling drives CD8+T cell exhaustion (TEX) in cancer and chronic infection. However, how the kinase cascades downstream of the T cell receptor drive exhaustion is not understood. We found that continuous agonism of protein kinase C (PKC) causes degradation of PKC theta, but not PKC eta, and induces terminal TEXcells. During chronic infection, PKC theta is necessary to maintain the progenitor exhausted (TEX-PROG) cells, and thus the antigen-specific T cell response, while agonism of PKC eta promotes terminal exhaustion (TEX-TERM)in vitroandin vivo. The cascades downstream of these kinases are distinct, with PKC theta promoting activity of canonical PKC targets in the MAPK and CDK families, while eta promotes activity of other targets, including casein kinase I G2 (CK1G2). Expression of an engineered, degradation-resistant PKC theta, or deletion of the gene encoding CK1G2, improves T cell function and tumor control. Our illustration of multiple therapeutic avenues arising from targeting PKC highlights its centrality in TEXdifferentiation and its clinical potential in cancer immunotherapy.

Highlights

PKC theta sustains T cell function while PKC eta promotes terminal exhaustion

PKC theta and eta drive distinct phospho-cascades to oppose each other’s differentiation instructions

An engineered, degradation-resistant PKC theta improves T cell responses in chronic infection and cancer

Ablation of kinase CK1G2 downstream of PKC eta improves anti-tumor T cell responses
Increases in Arctic extreme climatic events are linked to negative fitness effects on the local biota
Authors: Lemaire M , Bokhorst S. , Witheford A. , Macias-Fauria M. , Salguero-Gomez R.
Published: September 2024

1.

The Arctic harbours uniquely adapted biodiversity and plays an important role in climate regulation. Strong warming trends in the terrestrial Arctic have been linked to an increase in aboveground biomass (Arctic greening) and community-wide shifts such as the northwards-expansion of boreal species (borealisation). Whilst considerable efforts have been made to understand the effects of warming trends in average temperatures on Arctic biota, far fewer studies have focused on trends in extreme climate events and their biotic effects, which have been suggested to be particularly impactful during the Arctic winter months. Here, we present an analysis of trends in two ecologically-relevant winter extreme events –extreme winter warming and rain-on-snow, followed by a meta-analysis on the evidence base for their effects on Arctic biota. We show a strong increase in extreme winter warming across the entire Arctic and high variability in rain-on-snow trends, with some regions recently experiencing rain-on-snow for the first time whilst others seeing a decrease in these events. Ultimately, both extreme events show significant changes in their characteristics and patterns of emergence. Our meta-analysis –encompassing 178 effect sizes across 17 studies and 49 species– demonstrates that extreme winter warming and rain-on-snow induce negative impacts on Arctic biota, with certain taxonomic groups –notably angiosperms and chordates (mostly vertebrates)– exhibiting higher sensitivity than others. Our study provides evidence for both emerging trends in Arctic winter extreme climate events and significant negative biotic effects of such events –which calls for attention to winter weather variability under climate change in the conservation of Arctic biodiversity, whilst highlighting important knowledge gaps.
SEISMICgraph: a web-based tool for RNA structure data visualization
Authors: Fuchs Wightman Federico , Yang Grant , Martin des Taillades Yves J. , L’Esperance-Kerckhoff Casper , Grote Scott , Allan Matthew F. , Herschlag Daniel , Rouskin Silvi , Hagler Lauren D.
Published: September 2024

In recent years, RNA has been increasingly recognized for its essential roles in biology, functioning not only as a carrier of genetic information but also as a dynamic regulator of gene expression through its interactions with other RNAs, proteins, and itself. Advances in chemical probing techniques have significantly enhanced our ability to identify RNA secondary structures and understand their regulatory roles. These developments, alongside improvements in experimental design and data processing, have greatly increased the resolution and throughput of structural analyses. Here, we introduce SEISMICgraph, a web-based tool designed to support RNA structure research by offering data visualization and analysis capabilities for a variety of chemical probing modalities. SEISMICgraph enables simultaneous comparison of data across different sequences and experimental conditions through a user-friendly interface that requires no programming expertise. We demonstrate its utility by investigating known and putative riboswitches and exploring how RNA modifications influence their structure and binding. SEISMICgraph’s ability to rapidly visualize adenine-dependent structural changes and assess the impact of pseudouridylation on these transitions provides novel insights and establishes a roadmap for numerous future applications.

GRAPHICAL ABSTRACT
LRRC8 complexes are adenosine nucleotide release channels regulating platelet activation and arterial thrombosis
Authors: Tranter John D. , Mikami Ryan T. , Kumar Ashutosh , Brown Gavriel , Abd El-Aziz Tarek M. , Zhao Yonghui , Abraham Nihil , Meyer Chloe , Ajanel Abigail , Xie Litao , Ashworth Katrina , Hong Juan , Zhang Haixia , Kumari Tripti , Balutowski Adam , Liu Alice , Bark David , Nair Vinayak K. , Lasky Nina M. , Feng Yongmei , Stitziel Nathan O. , Lerner Daniel J. , Campbell Robert A. , Paola Jorge Di , Cho Jaehyung , Sah Rajan
Published: September 2024

Platelet shape and volume changes are early mechanical events contributing to platelet activation and thrombosis. Here, we identify single-nucleotide polymorphisms in Leucine-Rich Repeat Containing 8 (LRRC8) protein subunits that form the Volume-Regulated Anion Channel (VRAC) which are independently associated with altered mean platelet volume. LRRC8A is required for functional VRAC in megakaryocytes (MKs) and regulates platelet volume, adhesion, and agonist-stimulated activation, aggregation, ATP secretion and calcium mobilization. MK-specific LRRC8A cKO mice have reduced arteriolar thrombus formation and prolonged arterial thrombosis without affecting bleeding times. Mechanistically, platelet LRRC8A mediates swell-induced ATP/ADP release to amplify agonist-stimulated calcium and PI3K-AKT signaling via P2X1, P2Y1and P2Y12receptors. Small-molecule LRRC8 channel inhibitors recapitulate defects observed in LRRC8A-null plateletsin vitroandin vivo. These studies identify the mechanoresponsive LRRC8 channel complex as an ATP/ADP release channel in platelets which regulates platelet function and thrombosis, providing a proof-of-concept for a novel anti-thrombotic drug target.
Pancreatic cancer cells overexpressing interleukin 6 induce T-cell-mediated tumor clearance and durable anti-tumor immune response
Authors: Arneson-Wissink Paige C. , Bartlett Alexandra Q. , Mendez Heike , Zhu Xinxia , Dickie Jessica , McWhorter Matthew , Levasseur Peter R. , Diba Parham , Byrne Katelyn T. , Scott Gregory D. , Eil Robert , Grossberg Aaron J.
Published: September 2024

Tumor immune resistance is recognized as a contributor to low survivorship in pancreatic ductal adenocarcinoma (PDAC). We developed a novel murine model of spontaneous PDAC clearance, generated by overexpressing interleukin-6 (IL-6) in orthotopically implanted PDAC cancer cells (OT-PDACIL6). Circulating IL-6 was 100-fold higher in OT-PDACIL6than in OT-PDACparentalmice. OT-PDACIL6tumors were present at 5 days post-implantation, and undetectable by 10 days post implantation. Flow cytometry revealed increased T cells and NK cells, and decreased T regulatory cells in OT-PDACIL6as compared to OT-PDACparentaltumors. Increased lymphoid aggregates were apparent by histological assessment and may account for elevated T cell content. Antibody-based depletion of CD4+and CD8+T cells prevented tumor clearance and significantly reduced survival of OT-PDACIL6mice. The anti-tumor immune response to OT-PDACIL6rendered mice immune to re-challenge with OT-PDACparentaltumors. In high concentrations, IL-6 acts in opposition to previously described pro-tumorigenic effects by enhancing the T cell-mediated anti-tumor response to PDAC.

Statement of Significance

Interleukin 6 overexpression in pancreatic ductal adenocarcinoma cells induces T cell-driven tumor clearance that is rapid and durable. Supraphysiologic levels of interleukin 6 are sufficient to drive an anti-tumor immune microenvironment hallmarked by increased lymphoid aggregate formation, increased CD4 T cell abundance, and decreased Treg abundance.
Screen Cauchy–Riemann (SCR)-lightlike submanifolds of metallic semi-Riemannian manifolds
Authors: Shanker Gauree , Yadav Ankit , Kaur Ramandeep
Published: September 2024

Purpose

The screen Cauchy–Riemann (SCR)-lightlike submanifold is an important class of submanifolds of semi-Riemannian manifolds. It contains various other classes of submanifolds as its sub-cases. It has been studied under various ambient space. The purpose of this research is to study the geometry of SCR-lightlike submanifolds of metallic semi-Riemannian manifolds.

Design/methodology/approach

The article is divided into five sections. The first section is introductory section which represents brief overview of the conducted research of this article. The second section outlines the key results that are utilized throughout the paper. In section three, the definition of SCR-lightlike submanifold is constructed with one non-trivial example. In section four and five, the important results on integrability, totally geodesic foliations and warped product are given.

Findings

The SCR-lightlike submanifold is introduced. One non-trivial example is constructed which helps to understand the given structure. The necessary and sufficient conditions for the integrability and to be totally geodesic for various distributions are obtained. The necessary and sufficient conditions for induced connection on totally umbilical SCR-lightlike submanifolds to be a metric connection are discussed. Various results are found on totally umbilical SCR-lightlike submanifolds. Finally, the existence of the warped product lightlike submanifold of the type N⊥×λNT is studied.

Originality/value

SCR-lightlike submanifolds have been explored within ambient manifolds possessing various structures, such as Kaehler, Sasakian and Kenmotsu structures. In this article, we investigate this structure on submanifolds of metallic semi-Riemannian manifolds. This original and authentic research will aid researchers in advancing the study of semi-Riemannian manifolds.
Supply chain resilience during COVID-19 pandemic: role of market orientation, knowledge management orientation and innovative capability
Authors: Tukamuhabwa Benjamin , Makepu Ngobi Joel , Mutebi Henry , Tumukunde Ivan
Published: September 2024

Purpose

This paper explores the direct relationships between market orientation (MO), knowledge management orientation (KMO), innovative capability (IC) and supply chain resilience (SCRES). Moreover, the indirect effects of both MO and KMO on SCRES through IC are also examined.

Design/methodology/approach

A theoretical model developed from the extant literature was empirically validated through a cross-sectional survey of 195 manufacturing firms in Uganda during the COVID-19 pandemic. The data were analysed using partial least squares structural equation modelling (PLS-SEM).

Findings

The study found that there are positive and significant direct effects of MO and KMO on IC. KMO and IC have positive and significant effects on SCRES, while the positive relationship between MO and SCRES is non-significant. Furthermore, the results indicate that the effects of both MO and KMO on SCRES are partially mediated by IC.

Originality/value

Empirical evidence is provided on the antecedents of SCRES in a developing economy in the context of COVID-19. Moreover, a multidisciplinary model incorporating marketing, knowledge management and innovation literature to explain the SCRES phenomenon is validated. Further, the partial mediating role of IC is examined and confirmed.
Aeron dilemma of market selection
Authors: Kumar Anuj , Pujari Purvi , Gupta Nimit
Published: September 2024

Learning outcomes

This case study would enable the learners to identify and evaluate the factors impacting the strategic decision to enter international markets. The learners would be able to identify parameters such as level of competition, perception regarding foreign entrants and demand factors that are crucial for the form to consider while taking such an important decision. The case study will also allow learners to understand the challenges of an entrepreneurial journey.

Case overview/synopsis

This case study is an interesting story of two entrepreneurs’ dilemma of internationalization strategy of their firm Aeron. Their firm’s product Tilt Switch had a good international demand and both partners wished to capture this opportunity, post the COVID-19 pandemic. This case study shows how the firm looked into factors to study new international markets, balancing risk and opportunity. The case study highlights the important role of strategic planning in achieving successful internationalization by analysing various approaches to market entry and adaptation. The firm had a choice of either developing their domestic market India or going for international markets of the USA or European Union.

Complexity academic level

This case study is suitable for graduation and postgraduation courses.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 5: International Business.
The contest for workplace employee representation: still seeking answers?
Authors: Snook Jereme , Whittall Michael
Published: September 2024

Purpose

The purpose of this paper is to demonstrate union and non-union’s mechanisms ability to “contest” the realm of workplace employee representation at two UK sites. The paper directly compares one union and one non-union mechanism of employee representation at separate sites by employing three “dilemmas” of employee representation: confidentiality, challenge and trust. The paper contributes to enduring debates about the efficacy of employee voice in UK organisations.

Design/methodology/approach

The paper uses a qualitative and inductive case study approach in two organisations, drawing upon semi-structured interviews, archival documentation, company meetings and a trade union officer diary to record the employee representatives use of voice to influence company decision-making.

Findings

The paper shows how the union achieved improved pay and a more trusting relationship with managers in comparison to the non-union mechanism, which failed to influence managers’ decisions at the site and fell into demise.

Research limitations/implications

Limitations are that the paper covers one geographical area and interviews were made with employee representatives and HR and management. The access was limited by the respective case study management regime/s. The data are acknowledged as now historical but remain relevant as a means of understanding wider debates on employee representation and voice. These limitations are now acknowledged in the revised edition of the manuscript, as suggested by the reviewers.

Practical implications

The practical implications are that the paper shows how employee representatives face similar dilemmas in their operational roles and activities. If these dilemmas are managed with efficacy for members, then this can result in good outcomes for those members and legitimacy for the workplace employee representatives. We also suggest that the use of employee voice as a practical concept is seen here – the practical use of the factors comprising voice in the literature is used to show representatives' abilities to influence management decision-making.

Social implications

The significance of having a voice at work that raises the profile of employee representatives and their members emerges from this paper. An effective voice mechanism can promote improved employment relations in a workplace setting.

Originality/value

This paper develops knowledge about dilemmas as important and enduring issues for employee representatives, which, when inconsistently managed, can lose them the support of the workforce or, alternatively, empower them to challenge and sometimes alter management decisions.
Digital influencers in different cultural contexts: effects of authenticity and value perceptions
Authors: Gadekar Mahesh , Diallo Mbaye Fall , Osburg Victoria-Sophie
Published: September 2024

Purpose

Brands can build meaningful, effective connections with consumers through digital influencers. This paper aims to understand the factors determining digital influencers’ success concerning brand-related (i.e. intention to follow influencer advice) and influencer-related (i.e. intention to recommend the influencer) outcomes. We present a conceptual model derived from established theories and psychological reasoning, identifying influencer authenticity and perceived value as important antecedents. We present satisfaction with the influencer and influencer credibility as the psychological mechanism explaining why antecedents transform into favorable outcomes.

Design/methodology/approach

With structural equation modeling and two studies (N1 = 814; N2 = 685) relying on active followers from two countries (the UK and India), this paper examines the direct and indirect effects of the value and authenticity of digital influencers on followers’ behavioral outcomes and the cultural context’s potential moderating effect.

Findings

Authenticity and value of digital influencers positively affect intention to follow influencer advice and recommend the influencer. Such effects are mediated by follower satisfaction and influencer credibility. The effects of influencer authenticity and value on intentions to follow and recommend are not stronger in India than in the UK.

Originality/value

We contribute to the literature by presenting a theoretically informed framework capturing the antecedents of successful influencers and the importance of differentiating brand-related and influencer-related outcomes. Furthermore, our studies highlight that research findings about influencers’ impact may not be generalizable to other cultural contexts.
Implementing outsourcing strategies under a pandemic: the case of the nursing service industry
Authors: Wang Xiaoxiao , Liang Changyong , Chen Jingxian
Published: September 2024

Purpose

The pandemic has caused severe disruptions and significant losses in various industries. In particular, the nursing service industry has been greatly affected, leading to increased service costs and attrition of nursing service provider (NSP) residents. Although prior studies suggest that outsourcing may mitigate losses from disruptions, there still lacks a detailed analysis of whether and when to adopt such a disruption solution.

Design/methodology/approach

This study develops a two-period game-theoretical model to explore the impacts of demand and cost disruptions caused by the pandemic on NSPs’ operational strategies, suppliers’ strategy choices and equilibrium prices and demand.

Findings

The results present several novel managerial insights. First, we suggest that higher demand and cost disruptions decrease service demand, but do not necessarily prompt an NSP to outsource nursing services. Interestingly, we find that even when the service cost of the outsourcing strategy is low, the NSP may still insist on the in-house strategy. Additionally, the equilibrium strategy does not always result in lower prices and higher demand.

Originality/value

Our findings provide insightful takeaways for NSPs to cope with the pandemic in the nursing service industry. The results also offer theoretical support for other industries to recover from demand and cost disruptions.
Divergence in disability reporting: assessing SDG alignment in corporate sustainability disclosures
Authors: Ligorio Lorenzo , Palazzo Giampiero , Marchetti Simona
Published: September 2024

Purpose

This study aims to evaluate the contribution of companies on disability through sustainability reporting. In particular, the analysis evaluates the content of Sustainable Development Goals (SDGs) contribution on disability.

Design/methodology/approach

This study adopts the most recent Global Reporting Initiative (GRI) guidelines and the Agenda 2030 framework to measure corporate contribution on disability challenges via their disclosures. Next, a quality content analysis was conducted on the disability-related information disclosed.

Findings

Evidence revealed that while appearing compliant with the GRI indicators on disability, companies still struggle to effectively disclose and engage with disability-related topics, presenting a strong misalignment between quantity of information and quality of the information on the SDGs related challenges.

Originality/value

To the best of authors’ knowledge, this is the first study to explore corporate transparency on social inclusivity regarding disability-affected subjects by considering the divergence between reporting guidelines compliance and information quality.
Digital twins for enhanced construction project management
Authors: Aktürk Berkay , Irlayıcı Çakmak Pınar
Published: September 2024

Purpose

This paper aims to fill the research gap on digital twin technology and its broad applicability during construction by shedding light on its interaction with Building Information Modeling (BIM) from a construction project management perspective. It presented the true potential of the digital twins in the construction phase of the project lifecycle.

Design/methodology/approach

The paper employed a two-step methodology that included a comprehensive synthesis of the literature on digital twins through the construction management lens and a questionnaire survey to assess the impact of digital twin services brought to light on parallel BIM uses.

Findings

The paper provides validated applications and many advantages of the digital twin on construction project management. It suggests that the industry should take advantage of 10 digital twin services introduced to eliminate the low efficiency and lack of productivity that the construction industry is still facing.

Research limitations/implications

The paper is one of the rare and pioneering studies that addresses the interaction between the digital twin and BIM from a construction management perspective with a quantitative approach examining the reflection of academic publications on the industry and their reception among industry professionals.

Practical implications

The paper provides a meaningful definition for the industry by grounding the concept of digital twin in existing technologies and their practical applications. This provides a roadmap for managers to approach the problems and BIM limitations they need to overcome in their companies or projects with tailor-made solutions.

Originality/value

The paper is one of the pioneering quantitative studies that fulfills an identified need to investigate digital twin technology for construction management and its extensive applicability for quickly evolving construction sites.
Sir Walter Ralegh and the Art of War by Sea: Military Humanism and the Uses of the Early Modern Soldier‐Scholar
Authors: WOODCOCK MATTHEW
Published: September 2024

This article establishes the intellectual origins and underpinnings of the early modern soldier‐scholar in order to better understand the military humanist tradition within which Sir Walter Ralegh's writings on naval warfare and logistics were conceived and composed. By locating Ralegh within this tradition, the article provides a new critical framework for examining his dual identification with both the military and scholarly spheres. After discussing how the soldier‐scholar figure is indebted to the early modern intellectualisation of the art of war as an object of humanist discourse, this article examines how Ralegh adopts this figure as a means to seek preferment at court, beginning in the mid‐1590s following his fall from royal favour. Focusing on three distinct groups of naval writings, it argues that Ralegh positioned himself as an expert in the art of war by sea as a means of effacing differences in social status between himself and his contemporaries at court. It discusses his relationship with contemporary soldier‐scholars—including Sir Humphrey Gilbert, Robert Devereux, earl of Essex, and Henry Percy, earl of Northumberland—and demonstrates how Ralegh's expertise in naval matters combined personal experience, first‐hand information from well‐travelled mariners and extensive reading in classical and early modern military science.
IMPROVISING COVID RELIEF IN NEW DELHI: Rehearsal and Improvisational Capacity in Informal Student Networks
Authors: Dasgupta Anushka , van den Berg Marguerite
Published: September 2024

Building on qualitative interviews, this article brings into view how New Delhi university students organized improvised forms of Covid relief during the Delta coronavirus wave in the spring of 2021. Responding to a lack of care due to state negligence and a breakdown of public and private healthcare infrastructure, students coordinated access to crucial resources such as masks, other personal protective equipment and even oxygen through the use of social media, existing social networks, and practices developed in earlier moments of organizing. Using the lenses of improvisation, rehearsal and repair, this article documents how students improvised informal Covid relief. Conceptually, the article offers the framework of transposition to look at how improvisational capacity in a social network was shifted from one crisis to the next.
Synergistic effect of drying methods and ultrasonication on natural deep eutectic solvent extraction of phytochemicals from African spinach (Amaranthus hybridus) stem
Authors: Okonkwo Clinton E. , Olaniran Abiola F. , Esua Okon Johnson , Elijah Adeoye O. , Erinle Oluwakemi C. , Afolabi Yemisi Tokunbo , Olajide Olasunkanmi Peter , Iranloye Yetunde Mary , Zhou Cunshan
Published: September 2024

The study evaluated the combined effects of drying methods (air drying [AD], hot AD [HAD], microwave drying [MD], and freeze‐drying [FD]) and ultrasonication parameters (sonication temperature [STemp]: 40, 50, and 60°C) and heating time (STime: 60 and 120 min) on natural deep eutectic solvent (NADES) extraction of phytochemicals from Amaranthus hybridus stem. Increasing the STemp increased the extraction yield (ECY) of the phytochemicals for all drying methods but increase in the heating time reduced the ECY slightly. MD combined with 60°C ST showed the highest ECY (53%), whereas HAD combined with 40°C ST had the lowest ECY (18%). At 60 min heating time, increasing the ST from 40 to 50°C increased the total phenolic content (TPC) in the extract for most drying methods except MD, and a sonication time of 120 min showed a slightly higher TPC, especially for MD samples. At 60 min sonication, total flavonoid content (TFC, 800 mgQE/g) was highest for AD plus 50°C ST and lowest for AD combined with 60°C (100 mgQE/g), whereas for 120 min sonication, MD and AD with 50°C showed the highest TFC (690 mgQE/g). FD retained better some of the vitamins (thiamine, riboflavin, niacin) but MD retained better vitamin C. The antioxidant capacity was not so much different among the drying methods except for FD, which showed lower values. These results provide a theoretical basis for the synergistic applications of drying and ultrasonication during NADES extraction of phytochemicals from Amaranthus hybridus.
Egypt's position in the Russia–Ukraine war
Authors: Ragab Eman
Published: September 2024

This paper argues that Egypt's balancing position on the war on Ukraine is shaped by a combination of a rational analysis of the consequences of the war and a pre‐war vision of its role in the ongoing global transformation. The paper employs the framework of varied consequentialism to identify the main factors driving Egypt's balancing position. The first factor relates to Egypt's dependence on external partners, contributing to the vulnerability of its national security, which leaves minimal room for maneuvering in responding to external crises, including the war in Ukraine. The second factor relates to the negative implications of the war on Egypt's national food security. The third factor is the need for external support to contain the war's negative consequences, which raises questions about the reliability of the international partners. The paper also discusses how this balancing position has defined Egypt's response to the American and Russian visions of the new world order in the post‐Ukraine war period.
Russia's invasion of Ukraine: Nigeria's value‐driven and pragmatic indifferent stance
Authors: Ayodele Bonnie
Published: September 2024

Nigeria's response to the Russian invasion of Ukraine carried significant geopolitical weight within the Global South. Despite Western pressure, Nigeria adopted a carefully calibrated, value‐driven, pragmatic indifferent stance that avoided overtly condemning Russia. While denouncing the violation of Ukraine's territorial integrity, Nigeria emphasised the need for dialogue and diplomacy. This reflected Nigeria's pursuit of strategic domestic value‐driven foreign policy that has embedded non‐alignment principles and its Afrocentric worldview. Nigeria's position highlighted the challenge many Global South nations face in being caught between the West and Russia. Overtly backing either side could jeopardise their interests and economic ties. Nigeria aimed to uphold foreign policy principles and support international norms like sovereignty while keeping channels open with the West and Russian power blocs. Its position, which reflects Afrocentricism, bolstered its credentials as a leader representing the perspectives of the Global South. Its value‐driven and pragmatic indifferent stance provided a model for global order‐making, and its deft geopolitical balancing act allowed it to protect its interests while reinforcing its status as an influential force shaping the Global South's stance(s) on major international issues.
Endogenous technologies and productivity in rice production: Roles of social instability in Myanmar since 2021
Authors: Takeshima Hiroyuki , Aung Zin Wai , Masias Ian , Minten Bart
Published: September 2024

Despite technologies' critical roles in agricultural productivity, evidence is scarce on how conflict affects technology adoption and consequent agricultural productivity, often due to a lack of data in fragile states. Our study contributes to filling this knowledge gap by using unique large‐scale data on rice producers before and after a military coup in Myanmar in 2021 that led to a significant increase in conflicts in the country. We find that the increase in violent events including those in adjacent townships significantly changed the rice production function in both factor‐neutral and non‐neutral ways. Specifically, increased violent events have been generally associated with downward factor‐neutral shift in production function, and more importantly, increased output elasticity to agricultural capital (equipment) owned (in other words, reduced output resilience against capital ownership shocks). Our evidence also suggests that this has been led partly through reduced access to agricultural extension services, which would otherwise help farmers maintain productivity even with limited capital ownership by substituting it with human capital and skills. Our results consistently hold for both panel and cross‐sectional production functions across various specifications and particularly in Lower Myanmar. Results also indicate that lower mechanization service fees partly mitigate these effects.
Ascorbic acid 2‐glucoside improves survival, quality, and fertility of frozen‐thawed C57Bl/6J and C57Bl/6N mouse spermatozoa
Authors: Raspa Marcello , Paoletti Renata , Scavizzi Ferdinando
Published: September 2024

Background

Ascorbic acid 2‐glucoside (AA2G) is a stabilized form of ascorbic acid and a potent antioxidant. Ascorbic acid is present in the testes and epididymis and helps maintain the physiological integrity of reproductive organs. Its properties have been utilized to protect spermatozoa of different species from oxidative stress.

Materials and methods

Spermatozoa of C57Bl/6J and C57Bl/6N strains were frozen and analyzed, after thawing, by supplementing the capacitation medium with AA2G, both in the presence and absence of methyl‐β‐cyclodextrin (MBCD). The effect of treatment was evaluated by SCA System (Microptic) analyzing the velocity, vitality, morphology, and the DNA fragmentation. We also examined sperm capacitation (CTC), acrosome reaction (Coomassie Brillant Blue), and fertility (in vitro fertilization) of treated spermatozoa.

Results

AA2G improved sperm quality and fertility particularly in association with MBCD. We observed a significant increase of sperm motility, velocity, and vitality associated with an enhanced capacitation and acrosome reaction. These improvements resulted in a marked increase in in vitro fertilization success. Embryos obtained were cultured and reached normally the blastocyst stage.

Discussion

This study aimed to determine if AA2G could safeguard mouse spermatozoa during cryopreservation. We found a protective effect of AA2G that increased sperm survivability resulting in higher fertilization rate.

Conclusion

This newly improved protocol shows potential for reanimating cryopreserved GEMMs stored in mouse biobanks and international repositories, such as the European Mouse Mutant Archive (EMMA).

This can serve as a pivotal tool in fulfilling the 3Rs mission (replacement, reduction, and refinement), promoting ethical and humane research practices.
Interplay of leucocyte–platelet complexes and clinical response to eltrombopag in immune thrombocytopenia patients
Authors: Osuna‐Gómez Rubén , Zamora Carlos , Novelli Silvana , Garcia‐Pallarols Francesc , Rodriguez Yva , Domingo Abel , Canet Marta , Olivera Pavel , Mulet Maria , Cantó Elisabet , Valcarcel David , Sanchez‐Gonzalez Blanca , Vidal Silvia
Published: September 2024

Eltrombopag (ELT) is a thrombopoietin‐receptor agonist that stimulates platelet (PLT) production in patients with primary immune thrombocytopenia (ITP). One potential mechanism of ELT is modulating the inflammatory response by increasing PLTs binding to leucocytes. This study examined the effect of ELT on leucocyte–PLTs complexes in 38 ITP patients. Patients, predominantly females with a mean age of 59 years, underwent treatments like corticosteroids, intravenous immunoglobulin and splenectomy. Compared to healthy donors, ITP patients exhibited lower percentages of lymphocyte with bound PLTs, but similar monocyte‐ or neutrophil with bound PLTs. ELT treatment increased PLTs counts and all types of leucocyte with bound PLTs. Network analysis showed dynamic changes in leucocyte with bound PLTs relationships due to ELT. Machine learning indicated that higher percentages of monocytes with bound PLTs were linked to a better clinical response to ELT. A possible mechanism was an increased IL‐10 production in monocytes with bound PLTs from responder patients. This study provides insights into the immunological changes in ITP patients undergoing ELT and suggests potential predictive biomarkers for treatment response and disease monitoring.
The flavonoid resokaempferol improves insulin secretion from healthy and dysfunctional pancreatic β‐cells
Authors: Gautheron Guillaume , Péraldi‐Roux Sylvie , Vaillé Justine , Belhadj Sahla , Patyra Andrzej , Bayle Morgane , Youl Estelle , Omhmmed Soufiyan , Guyot Mélanie , Cros Gérard , Guichou Jean‐Francois , Uzan Benjamin , Movassat Jamileh , Quignard Jean‐François , Neasta Jérémie , Oiry Catherine
Published: September 2024

Background and Purpose

The pharmacology of flavonoids on β‐cell function is largely undefined especially in the context of defective secretion of insulin. We sought to identify flavonoids that increased the insulin‐secreting function of β‐cells and to explore the underlying mechanisms.

Experimental Approach

INS‐1 β‐cells in culture and islets of Langerhans isolated from control and diabetic male rats were used for insulin secretion experiments. Pharmacological and electrophysiological approaches were used for mechanistic studies.

Key Results

Among a set of flavonoids, exposure of INS‐1 β‐cells to resokaempferol (ResoK) enhanced glucose‐stimulated insulin secretion and therefore we further characterised its activity and its pharmacological mechanism. ResoK glucose‐dependently enhanced insulin secretion in INS‐1 β‐cells and pancreatic islets isolated from rats. Mechanistically, whole cell patch clamp recordings in INS‐1 cells showed that ResoK rapidly and dose‐dependently enhanced the L‐type Ca2+ current whereas it was inactive towards T‐type Ca2+ current. Accordingly, pharmacological inhibition of L‐type Ca2+ current but not T‐type Ca2+ current blocked the effects of ResoK on glucose‐stimulated insulin secretion. ResoK was still active on dysfunctional β‐cells as it ameliorated glucose‐stimulated insulin secretion in glucotoxicity‐induced dysfunctional INS‐1 cells and in pancreatic islets isolated from diabetic rats.

Conclusion and Implications

ResoK is a glucose‐dependent activator of insulin secretion. Our results indicated that the effects of ResoK on insulin secretion involved its capacity to stimulate L‐type Ca2+ currents in cultured β‐cells. As ResoK was also effective on dysfunctional β‐cells, our work provides a new approach to stimulating insulin secretion, using compounds based on the structure of ResoK.
Protection of the genome and the central exome by peripheral non‐coding DNA against DNA damage in health, ageing and age‐related diseases
Authors: Qiu Guo‐Hua , Fu Mingjun , Zheng Xintian , Huang Cuiqin
Published: September 2024

DNA in eukaryotic genomes is under constant assault from both exogenous and endogenous sources, leading to DNA damage, which is considered a major molecular driver of ageing. Fortunately, the genome and the central exome are safeguarded against these attacks by abundant peripheral non‐coding DNA. Non‐coding DNA codes for small non‐coding RNAs that inactivate foreign nucleic acids in the cytoplasm and physically blocks these attacks in the nucleus. Damage to non‐coding DNA produced during such blockage is removed in the form of extrachromosomal circular DNA (eccDNA) through nucleic pore complexes. Consequently, non‐coding DNA serves as a line of defence for the exome against DNA damage. The total amount of non‐coding DNA/heterochromatin declines with age, resulting in a decrease in both physical blockage and eccDNA exclusion, and thus an increase in the accumulation of DNA damage in the nucleus during ageing and in age‐related diseases. Here, we summarize recent evidence supporting a protective role of non‐coding DNA in healthy and pathological states and argue that DNA damage is the proximate cause of ageing and age‐related genetic diseases. Strategies aimed at strengthening the protective role of non‐coding DNA/heterochromatin could potentially offer better systematic protection for the dynamic genome and the exome against diverse assaults, reduce the burden of DNA damage to the exome, and thus slow ageing, counteract age‐related genetic diseases and promote a healthier life for individuals.
Impact of glucagon‐like peptide‐1 receptor agonists on diabetic retinopathy: A meta‐analysis of clinical studies emphasising retinal changes as a primary outcome
Authors: Kapoor Ishani , Sarvepalli Swara M. , D'Alessio David A. , Hadziahmetovic Majda
Published: September 2024

Background

To determine if glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are associated with the development and progression of diabetic retinopathy (DR).

Methods

A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP‐1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta‐analysis was pooled using a random‐effects model.

Results

Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP‐1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP‐1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01).

Conclusion

Our findings indicate no elevated risk of incidence of DR linked to GLP‐1RA compared to insulin. In fact, GLP‐1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP‐1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c – a phenomenon not specific to GLP‐1RA and warrants further investigation.