bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bispecific antibody targeting of lipid nanoparticles
Authors: Amabile Angelo , Phelan Matthew , Yu Zhixin , Silva Pedro , Marks Adam , Morla-Folch Judit , Sohn Moah , Mollaoglu Gurkan , Falcomata Chiara , Teunissen Abraham J P , Brody Joshua D , Dong Yizhou , Brown Brian D. 
Published: December 2024

AbstractLipid nanoparticles (LNP) are the most clinically advanced non-viral gene delivery system. While progress has been made for enhancing delivery, cell specific targeting remains a challenge. Targeting moieties such as antibodies can be chemically-conjugated to LNPs however, this approach is complex and has challenges for scaling up. Here, we developed an approach to generate antibody-conjugated LNPs that utilizes a bispecific antibody (bsAb) as the targeting bridge. As a docking site for the bsAb, we generated LNPs with a short epitope, derived from hemagglutinin antigen (HA), embedded in the PEG component of the particle (LNPHA). We generated bsAb in which one domain binds HA and the other binds different cell surface proteins, including PD-L1, CD4, CD5, and SunTag. Non-chemical conjugation of the bsAb and LNP resulted in a major increase in the efficiency and specificity of transfecting cells expressing the cognate target. LNP/bsAb mediated a 4-fold increase inin vivotransfection of PD-L1 expressing cancer cells, and a 26-fold increase in ex vivo transfection of quiescent primary human T cells. Additionally, we created a universal bsAb recognizing HA and anti-rat IgG2, enabling LNP tethering to off-the-shelf antibodies such as CD4, CD8, CD20, CD45, and CD3. By utilizing a molecular dock and bsAb technology, these studies demonstrate a simple and effective strategy to generate antibody-conjugated LNPs, enabling precise and efficient mRNA delivery.
Identifying the Brain Circuits that Regulate Pain-Induced Sleep Disturbances
Authors: Lynch Nicole , De Luca Roberto , Spinieli Richard L , Rillosi Enrico , Thomas Renner C , Sailesh Samuel , Gangeddula Nishta , Lima Janayna D , Bandaru Sathyajit , Arrigoni Elda , Burstein Rami , Thankachan Stephen , Kaur Satvinder 
Published: December 2024

AbstractPain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours. This relationship is facilitated by the transmission of nociceptive signals through the spino-parabrachial pathways, converging at the wake-active PBelCGRP(parabrachial nucleus expressing Calcitonin Gene-Related Peptide) neurons, known to gate aversive stimuli. However, it has never been tested whether the targeted blocking of this wake pathway can alleviate pain-induced sleep disturbances without increasing sleepiness. Therefore, we next used selective ablations or optogenetic silencing and identified the key role played by the glutamatergic PBelCGRPin pain-induced sleep disturbances. Inactivating the PBelCGRPneurons by genetic deletion or optogenetic silencing prevented these sleep disturbances in both pain models. Furthermore, to understand the wake pathways underlying the pain-induced sleep disturbances, we silenced the PBelCGRPterminals at four key sites in the substantia innominata of the basal forebrain (SI-BF), the central nucleus of Amygdala (CeA), the bed nucleus of stria terminalis (BNST), or the lateral hypothalamus (LH). Silencing of the SI-BF and CeA also significantly reversed pain-induced sleep loss, specifically through the action on the CGRP and NMDA receptors. This was also confirmed by site-specific blockade of these receptors pharmacologically. Our results highlight the significant potential for selectively targeting the wake pathway to effectively treat pain and sleep disturbances, which will minimize risks associated with traditional analgesics.One sentence summaryParabrachial CGRP neurons regulate awakenings to pain.
A cytochrome P450 involved in apocarotenoid signaling enhances plant photosynthetic capacity and photooxidative stress tolerance
Authors: Tiwari Madhu , Ksas Brigitte , Légeret Betrand , Caffarri Stefano , Havaux Michel 
Published: December 2024

Abstractβ-cyclocitric acid and its precursor β-cyclocitral are signaling apocarotenoids which trigger defense and detoxification mechanisms enhancing plant tolerance to abiotic stresses. From a transcriptomic analysis of Arabidopsis plants exposed to each apocarotenoid over several exposure times, we identified a gene (CYP81D11) encoding a cytochrome P450 that is strongly induced under all conditions and is under the control of the TGAII-SCL14 transcription regulator. Overexpressing theCYP81D11gene in Arabidopsis led to a very tolerant phenotype to high light stress while aCYP81D11- deficient mutant was photosensitive. The transcriptomic profile of theCYP81D11overexpressor revealed a selective upregulation of genes related to photosynthesis and the response to high light stress. Photosynthetic electron transport, CO2fixation and biomass production were noticeably improved by high expression levels ofCYP81D11. These effects occurred in high light, not in low light, and were associated with a noticeable reduction of singlet oxygen photoproduction. These findings indicate that CYP81D11 is a key component of β-cyclocitral-induced stress tolerance, acting through enhancement of the photosynthetic capacity of leaves. This gene could be a new target for improving photosynthesis, particularly in sunny environments.
Long-Term Colonization Dynamics of ProbioticAliivibriospp. in Atlantic Salmon (Salmo salar) Following Bath Administration
Authors: Steen Dobloug Marius , Iakhno Stanislav , Foyn Nørstebø Simen , Evensen Øystein , Sørum Henning 
Published: December 2024

AbstractUlcerative conditions present a major challenge in Norwegian salmon farming. Probiotic Aliivibrio species have previously been demonstrated to provide health benefits in both Atlantic salmon and lumpfish, although the underlying mechanisms and the host-bacteria interactions remain unclear. This study aimed to investigate whether these bacteria could colonize Atlantic salmon following bath administration, determine the tissue tropism, and assess the duration of colonization. We examined the host microbiota using culture-based methods, qPCR and immunohistochemistry techniques specifically designed to target the applied Aliivibrio strains. Our findings reveal that the probiotic bacteria can successfully colonize Atlantic salmon and persist for at least nine months post-administration. We identified the administered strains in the skin and underlying tissue with all three methods. The probiotics were also identified in the distal intestine and the visceral organs. Additionally, we isolated the probiotic Aliivibrio species from mixed cultures in ulcerated areas. While viable bacteria were recoverable from recently euthanized fish, tissue decay promoted bacterial recovery of the administered species across all experiments. Given prior evidence on ulcer reduction associated with these probiotics, competitive exclusion appears to be a plausible mechanism of action, though further investigation is warranted.
The IQGAP1-Claudin Cell Junction Axis in Cisplatin-induced Kidney Damage
Authors: Barudi Yusuf , Fan Xiuzhen , Jenkins Kenneth W. , Dey Shubhra Kanti , Yakirevich Evgeny , Osman Mahasin A 
Published: December 2024

AbstractKidney damage resulting from nephrotoxicity is a major side effect of chemotherapy. Cisplatin is an effective antineoplastic agent broadly used in oncology where it interferes with DNA replication in dividing cells, however, its mechanism in kidney damage remains unclear. We tested the hypothesis that cisplatin displaces cell-contact proteins such as IQGAP1-claudin complex in the kidney tubules, causing epithelial cell dissociation and kidney damage. Employing a multifaceted approach, using mutant analyses and optimal cisplatin dose, this hypothesis was tested in cell culture andiqgap1−/-mouse models. Cisplatin inhibited cell proliferation and migration in an IQGAP1-dependent manner, displaced IQGAP1 from cell junctions and altered the expression level of key junctional markers, including claudins 2/4/8 and nephrin. Similar effects were observed in animal models where cisplatin treatment and loss of IQGAP1 had additive effects. These functional outcomes are accounted for by suppression of Akt1/PKB survival and ERK1/2 proliferation signals and activation of JNK-GSK3αβ stress and inflammatory signal, widely implicated in kidney injury. These findings present IQGAP1-claudin axis as biomarkers and therapeutic targets in kidney damage and pave the way for formulating new analogs that eliminate cisplatin adverse side effects while preserving its antineoplastic efficacy.
Shape-constrained, changepoint additive models for time series omics data with cpam
Authors: Yates Luke A. , Humphreys Jazmine L. , Charleston Michael A. , Smith Steven M. 
Published: December 2024

AbstractTime series omics experiments are critical for the study of a wide range of biological processes such as cell differentiation and developmental programs or responses to pathogens and environmental cues. While statistical tools for differential analysis across static conditions have matured, comparable comprehensive methodology is lacking for time series data. Here, we introducecpam, a novel time series method and user-friendly software that performs temporal differential analysis of omics data for case-only or case-control time series, incorporating quantification uncertainty. Powerful features ofcpaminclude changepoint detection and shape-constrained temporal trend estimation to allocate omics data into similar clusters. Performance evaluation shows thatcpamoutperforms existing time series methods in terms of control of the false discovery rate versus power to detect temporal changes and accurate changepoint estimation. In particular, we find that trend-based models provide superior performance compared to pairwise comparisons, even with as few as six time points. The software provides an interactive interface with modern customizable visualisations, offering both graphical and statistical insight into complex molecular processes. Application to published transcriptome data illustrates RNA isoform-level modelling together with high resolution clustering during human embryogenesis and the identification of 910 novel genes differentially expressed in response to excess light in Arabidopsis. This method has the potential for application to a range of omics data, including single-cell analyses via pseudobulked data, providing the analytical power to reveal complex temporal patterns of gene expression in any biological system.
Leveraging metaverse knowledge in the gig economy: a social cognitive perspective on freelancer engagement and performance
Authors: Akhtar Maria , Abbas Khan Naseer , Khan Azmat Yar , Khan Asfand Yar 
Published: December 2024

Purpose
This study explores the impact of metaverse knowledge on freelancer engagement and performance within the gig economy, drawing upon the theoretical framework of social cognitive theory. The authors investigate the mediating role of freelancer engagement in the relationship between metaverse knowledge and performance, further examining the moderating influence of freelancer experience on these relationships.

Design/methodology/approach
Using a convenient sampling technique, data was collected through questionnaire from 301 freelancers working on various virtual platforms in Pakistan using a five-point Likert scale. Smart PLS 4.0 was used to analyze the data.

Findings
The findings reveal positive direct effect of metaverse knowledge on both freelancer engagement and performance. In addition, freelancer engagement significantly mediates the relationship between metaverse knowledge and performance. Furthermore, the findings affirm that the freelancers experience serves as a moderating factor in the relationship between metaverse knowledge, engagement and performance by indicating positive impact.

Originality/value
This study contributes a novel perspective to the gig economy literature by elucidating the underlying mechanisms through which metaverse knowledge drives freelancer performance via engagement. By examining the unique role of the metaverse in the gig context, the study offers valuable theoretical and practical implications for both scholars and practitioners seeking to understand and enhance freelancer engagement and performance in this evolving digital landscape.
Barriers to the adoption of sustainable construction materials in Zimbabwe
Authors: Moyo Tirivavi , Mudombo Mable Vongai , Omer Mazen M. , Moyo Cynthia 
Published: December 2024

PurposeThe built environment contributes to environmental concerns, including carbon emissions, with traditional construction materials being problematic. Adopting sustainable construction materials (SCMs) is envisaged; however, barriers exist. Hence, this study sought to determine significant barriers to adopting SCMs in Zimbabwe.Design/methodology/approachAn online questionnaire survey of construction professionals in consultancy firms and semi-structured interviews with key informants in Zimbabwe and Africa were instituted. Mean score analysis, normalisation values and exploratory factor analysis were quantitatively used to determine significant barriers. Content analysis of qualitative data from key informants was used to triangulate the findings.FindingsFrom the normalisation (with values > 0.90) and thematic analysis, a lack of incentives, training and government support were exposed as the most critical barriers. The factor analysis revealed seven significant components: governmental policy, finance and research support-related; sustainable construction material supply chain-related; green building policy and capacitation-related; change and trust-related; cost and complexity-related; project execution and investment-related and awareness and demand-related.Research limitations/implicationsThe insights of construction professionals from construction companies were not solicited. However, construction consultancy professionals who have a more significant influence on adopting SCMs were included. The government and clients are most critical in promoting the adoption of SCMs through enacting relevant policies and establishing buy-in.Originality/valueAccording to the authors’ knowledge, this is the first study to determine barriers to adopting SCMs through the contribution of key informants from various countries within the African continent.
The role of work engagement and psychological safety in how socially responsible human resources management affects employee voice behaviour
Authors: Silva Vítor Hugo , Duarte Ana Patrícia 
Published: December 2024

Purpose
This study aims to explore the role of socially responsible human resource management (SRHRM) as a key driver of employee voice behaviour. The hypotheses included that these human resources management (HRM) practices strengthen employees’ motivation to voice their opinions by increasing their work engagement (WE), thereby encouraging them to share their ideas and concerns about their organization more actively. The hypotheses also proposed that this effect is especially pronounced when employees experience a heightened sense of psychological safety.

Design/methodology/approach
A survey-based correlational study was conducted with a sample of 289 participants to analyse the proposed relationships between the selected variables.

Findings
The results indicate that SRHRM and WE are significantly associated with both promotive and prohibitive voice behaviour among employees. In addition, the moderated mediation model revealed that employees who perceive their organization as adopting SRHRM practices display higher levels of WE, which in turn increases these individuals’ likelihood of engaging in both types of voice behaviour. This relationship is particularly strong for promotive voice when employees experience high levels of organizational psychological safety.

Research limitations/implications
The findings are limited by the cross-sectional research design, which restricts causal inference.

Practical implications
By adopting people-centred HRM practices, organizations can foster psychologically safe environments that enhance employees’ willingness to engage in behaviour beneficial to their organization, such as WE and voice behaviours.

Originality/value
The results highlight the critical role of SRHRM and offer evidence-based insights into how interventions can foster positive employee behaviours and attitudes, including WE and voice behaviour.
Two secretory T2 RNases from a fungal pathogen target distinct insect cell transmembrane proteins to cause cytotoxicity
Authors: Yue Yong , Zhao Xin , Lu Zhuoyue , Dou Wei , Luo Zhibing , Lei Kangmin , Xu Dan , Zhang Yongjun 
Published: December 2024

AbstractFungal pathogens produce secretory ribonuclease (RNase) T2 proteins during infection, which contribute to fungal virulence via their enzyme functions in degradation of host cell RNA. However, the details of those proteins entering the host cells are unclear. Our previous study demonstrated that the two secretory RNase T2 members, BbRNT2 and BbTrv, produced by the insect fungal pathogen Beauveria bassiana, caused cytotoxic damage to insect cells and contributed to fungal virulence. Here, the Spodoptera frugiperda ovarian epithelial cells (sf9 cells) were used as models to investigate the interactions of the two fungus‐produced RNase T2 proteins with the insect cells. Two transmembrane proteins, an ABC transporter (SfABCG) and an Innexin 7‐like protein (Sfinx), were identified from the sf9 cells as interacting with BbRNT2 and BbTrv, respectively, through protein immunoprecipitation, yeast‐two hybrid tests and protein pull‐down assays. Although a slight decrease in the sf9 cell viability was examined by transfection of RNA interference of SfABCG or Sfinx, the transfected cells displayed a dramatically decreased sensitivity to BbRNT2 or BbTrv, suggesting the requirement of the two transmembrane proteins for BbRNT2 and BbTrv to enter the insect cells. These results reveal a mechanism of the cytotoxic molecules, T2 RNases, produced by the fungal pathogen, entering the insect cells via interaction with specific insect cell transmembrane proteins and causing cytotoxic damage.
The Future of China‐Gulf Solar and Wind Supply Chains
Authors: Sim Li‐Chen , Griffiths Steven 
Published: December 2024

ABSTRACTThis paper examines the medium‐term trajectory of China‐Gulf renewable energy supply chains amid growing global trade restrictions on China. The research explores how the Arab Gulf states, key collaborators in China's renewable energy sector, navigate these challenges, focusing on the dominance of China in global supply chains for solar and wind components. Using a demand‐pull, supply‐push framework, qualitative analysis assesses two potential scenarios: ‘Blue Sky’, where China‐Gulf supply chains grow stronger through ambitious renewable energy targets and expanded foreign direct investment, and ‘Sand Storm’, where geopolitical tensions and export restrictions could weaken these ties. The findings indicate that while supply chain engagement with China has risks, on balance China‐Gulf supply solar and wind technology supply chains are currently robust and projected to remain so in the future. The study concludes with policy recommendations for strengthening China's engagement with the broader Global South, highlighting opportunities for countries as they scale up domestic renewable energy deployment.
Identification and characterisation of Zucchini yellow fleck virus and a novel Nepovirus from next‐generation sequencing of mixed virus infections in cucumbers (Cucumis sativus) from Crete
Authors: James Anthony , Kryovrysanaki Nikoleta , Andronis Christos , Pappi Polyxeni G. , Kalantidis Kriton , Katsarou Konstantina 
Published: December 2024

AbstractCucumbers are susceptible to infections with many characterised virus species. In some cases, mixed virus infections occur and produce novel symptoms. In Greece, routine screening is carried out when virus infection is suspected, or novel symptoms are observed in the field. To identify the viruses associated with distinct symptoms observed in samples from commercial cucumber production areas on the island of Crete, Greece, we carried out high‐throughput sequencing (HTS) from a pool of six samples. Following assembly and BLAST analysis, we identified at least seven viruses based on similarity to published sequences. Two of these sequences represented novel, near‐complete genomes of a putative new nepovirus and of zucchini yellow fleck virus (ZYFV). To confirm the HTS results, the six samples were screened for all identified viruses, and their presence was confirmed through Sanger sequencing of PCR products. The full‐length genomes of both the nepovirus and ZYFV were amplified by PCR and confirmed by Sanger sequencing. We have generated the complete genome of a novel nepovirus from cucumber as well as the first complete genome sequence of a cucumber‐infecting ZYFV isolate from Crete. The nepovirus was mechanically transmissible to Nicotiana benthamiana and induced typical cytopathological modifications consistent with virus infection, as revealed by TEM studies. We propose to name this new virus Cucumber nepovirus A (CuNVA).
Rare but relevant: Nitrous oxide and peripheral neurotoxicity, what do we know?
Authors: Brunt Tibor M. , van den Brink Wim , van Amsterdam Jan 
Published: December 2024

AbstractNitrous oxide (N2O), used medically as an anaesthetic, has gained popularity as a recreational drug, with rising prevalence particularly among young adults. While its reinforcing and addictive potential remains debated, N2O is proven to be neurotoxic, especially with prolonged, heavy use, which is often unexpected for users. The neurotoxicological mechanism underlying N2O‐induced neurotoxicity involves inactivation of vitamin B12 (cobalamin), which disrupts methionine synthesis, essential for maintaining the myelin sheath. This can result in demyelinating diseases, including generalized demyelinating polyneuropathy (GDP). Clinical incidence of N2O‐induced peripheral neuropathy is largely unknown, although some research suggests it is not uncommon. Treatment includes immediate cessation of N2O use and vitamin B12 supplementation. Although this treatment often reverses damage, residual symptoms such as limb weakness may persist. Additionally, genetic and dietary factors, such as vitamin B12 deficiency, may heighten individual vulnerability for N2O's detrimental effects.
Non‐daily contraception: Reinforcing the choice of users and addressing unmet needs of reproductive health
Authors: Kopp Kallner Helena , Lindh Ingela , Gemzell‐Danielsson Kristina 
Published: December 2024

AbstractDespite great societal efforts promoting female autonomy, Sweden still faces unmet contraceptive needs, with abortion rates being the highest in the Nordic countries. In this commentary, we discuss using non‐daily contraception options to combat these unmet needs. Non‐daily methods include transdermal (i.e., patch), ring, injectables, and long‐acting reversible contraception (LARC). Numerous studies have revealed that users prefer non‐daily methods, and studies implementing structured counseling have revealed an increase in non‐daily methods. Relative to LARC, the patch and the ring are non‐daily parenteral methods that offer the possibility for self‐management. Ultimately, client‐centered counseling and shared decision‐making are crucial for increasing awareness of all methods and enhancing method utilization and adherence. Finally, dispelling myths surrounding reversible hormonal contraception is essential for empowering women to make informed choices and improving overall reproductive health outcomes.