bluuebunny/crossref_metadata_2025 huggingface dataset:
Survivin modulates stiffness-induced vascular smooth muscle cell motility
Authors: Mousso Thomas , Rice Kalina , Tumenbayar Bat-Ider , Pham Khanh , Heo Yuna , Heo Su Chin , Lee Kwonmoo , Lombardo Andrew T , Bae Yongho
Published: December 2024

Arterial stiffness is a key contributor to cardiovascular diseases, including atherosclerosis, restenosis, and coronary artery disease, it has been characterized to be associated with the aberrant migration of vascular smooth muscle cells (VSMCs). However, the underlying molecular mechanisms driving VSMC migration in stiff environments remain incompletely understood. We recently demonstrated that survivin, a member of the inhibitor of apoptosis protein family, is highly expressed in both mouse and human VSMCs cultured on stiff polyacrylamide hydrogels, where it modulates stiffness-mediated cell cycle progression and proliferation. However, its role in stiffness-dependent VSMC migration remains unknown. To assess its impact on migration, we performed time-lapse video microscopy on VSMCs seeded on fibronectin-coated soft and stiff polyacrylamide hydrogels, mimicking the physiological stiffness of normal and diseased arteries, with either survivin inhibition or overexpression. We observed that VSMC motility increased under stiff conditions, while pharmacologic or siRNA-mediated inhibition of survivin reduced stiffness-stimulated migration to rates similar to those observed under soft conditions. Further investigation revealed that cells on stiff hydrogels exhibited greater directional movement and robust lamellipodial protrusion compared to those on soft hydrogels. Interestingly, survivin-inhibited cells on stiff hydrogels showed reduced directional persistence and lamellipodial protrusion compared to control cells. We also examined whether survivin overexpression alone is sufficient to induce cell migration on soft hydrogels, and found that survivin overexpression modestly increased cell motility and partially rescued the lack of directional persistence compared to GFP-expressing control VSMCs on soft hydrogels. In conclusion, our findings demonstrate that survivin plays a key role in regulating stiffness-induced VSMC migration, suggesting that targeting survivin and its signaling pathways could offer therapeutic strategies for addressing arterial stiffness in cardiovascular diseases.
Long-read genomics reveal extensive nuclear-specific evolution and allele-specific expression in a dikaryotic fungus
Authors: Tam Rita , Möller Mareike , Luo Runpeng , Luo Zhenyan , Jones Ashley , Periyannan Sambasivam , Rathjen John P. , Schwessinger Benjamin
Published: December 2024

Phased telomere to telomere (T2T) genome assemblies are revolutionising our understanding of long hidden genome biology “dark matter” such as centromeres, rDNA repeats, inter-haplotype variation, and allele specific expression (ASE). Yet insights into dikaryotic fungi that separate their haploid genomes into distinct nuclei is limited. Here we explore the impact of dikaryotism on the genome biology of a long-term asexual clone of the wheat pathogenic fungusPuccinia striiformisf. sp.tritici. We use Oxford Nanopore (ONT) duplex sequencing combined with Hi-C to generate a T2T nuclear-phased assembly with >99.999% consensus accuracy. We show that this fungus has large regional centromeres enriched in LTR retrotransposons, with a single centromeric dip in methylation that suggests one kinetochore attachment site per chromosomes. The centromeres of chromosomes pairs are most often highly diverse in sequence and kinetochore attachment sites are not always positionally conserved. Each nucleus carries a unique array of rDNAs with >200 copies that harbour nucleus-specific sequence variations. The inter-haplotype diversity between the two nuclear genomes is caused by large-scale structural variations linked to transposable elements. Nanopore long-read cDNA analysis across distinct infection conditions revealed pervasive allele specific expression for nearly 20% of all heterozygous gene pairs. Genes involved in plant infection were significantly enriched in ASE genes which appears to be mediated by elevated CpG gene body methylation of the lower expressed pair. This suggests that epigenetically regulated ASE is likely a previously overlooked mechanism facilitating plant infection. Overall, our study reveals how dikaryotism uniquely shapes key eukaryotic genome features.
NFAT2 drives both Orai3 transcription and protein degradation by harnessing the differences in epigenetic landscape
Authors: Raju Sharon , Sharma Akshay , Ranjan Gyan , Motiani Rajender K
Published: December 2024

The functional significance of any protein in physiological processes and pathological conditions is largely dependent on its expression profile. Therefore, nature has evolved several autonomous mechanisms to regulate protein expression such as transcription, translation, post-translational modifications and epigenetic changes. These processes are typically controlled by distinct molecular players with no overlapping roles. Here, we reveal that same transcription factor, NFAT2 regulates both transcription and lysosomal degradation of Orai3 oncochannel in a context dependent manner. We demonstrate that NFAT2 drives Orai3 transcription and thereby increases Orai3 levels in non-metastatic cancerous cells. While in invasive and metastatic cancerous cells, NFAT2 induces Orai3 lysosomal degradation by transcriptionally enhancing the levels of MARCH8 E3 ubiquitin ligase. Our biochemical and super-resolution microscopy data show that MARCH8 physically interacts with Orai3 eventually resulting in its degradation. Mechanistically, the dichotomy in regulation of Orai3 expression emerges from the differences in the epigenetic landscape of MARCH8. We uncover that the MARCH8 promoter is highly methylated in non-metastatic cancerous cells and hence NFAT2 does not induce MARCH8 mediated Orai3 degradation in these cells. Importantly, we demonstrate that MARCH8 restricts pancreatic cancer metastasis by targeting Orai3 degradation thereby highlighting pathophysiological importance of this signaling module. Taken together, we report a unique and clinically relevant scenario wherein nature has commissioned the same transcription factor to both enhance and curtail the expression of a target protein.

Highlights

➢ NFAT2 transcriptionally upregulates Orai3 Ca2+channel in non-metastatic cells

➢ NFAT2 induces Orai3 lysosomal degradation via MARCH8 E3 ubiquitin ligase in metastatic cells

➢ The dichotomy in NFAT2’s function is an outcome of differences in the methylation status of MARCH8 promoter

➢ MARCH8 inhibits pancreatic cancer metastasis by driving Orai3 degradation

Graphical Abstract
Effect of peer-group participation on Knowledge about condoms among adolescent girls in rural Eastern Ethiopia: a community-based repeated cross-sectional study
Authors: Fasil Nebiyou , Worku Alemayehu , Oljira Lemessa , Tadesse Amare Worku , Berhane Yemane
Published: December 2024

Adolescent girls are at high risk of acquiring sexually transmitted infections (STIs), including the human immunodeficiency virus (HIV). Global evidence indicates significance of comprehensive sexual education in empowering adolescents with accurate knowledge regarding safe sexual practices. Adolescents living in rural areas, particularly have inadequately developed life skills; limited health promotion knowledge and are at risk of being coerced into sexual relationships. The study aimed to assess the effect of peer group participation on improving knowledge about condoms among adolescent girls in rural eastern Ethiopia. The study analyzed data from a repeated cross-sectional study involving 3186 and 3290 adolescent girls during the baseline period (2016) and the endline period (2019), respectively. The respondents were adolescent girls aged 13–17 years old. The study’s outcome was knowledge about condoms, which was assessed using 3-item questions. A weighted multivariable logistic regression analysis was used to examine the effect of peer group participation on improving knowledge about condoms by controlling for potential confounders. Statistical significance was set at a p-value <0.05. The magnitude of good knowledge about condoms among peer-group participants was 23% higher in the endline compared to the baseline. The odds of having good knowledge about condoms among girls who participated in an organized peer group were 2.15 times higher than those who didn’t participate (AOR: 2.15, 95% CI: 1.42, 3.26). Moreover, the odds of having good knowledge about condoms among those who reported high confidence in perceived communication skills were 1.68 times higher than those who reported no or little confidence (AOR: 1.68, 95% CI: 1.33, 2.13). Peer-group participation improved knowledge about condoms. Girls with high confidence in their perceived communication skills also had better knowledge about condoms. Peer-group education interventions have the potential to improve condom knowledge and thus improve sexual and reproductive health outcomes of adolescent girls. Further studies are needed in other contexts to inform intervention scale-up.
Complexity of the neutrophil transcriptome in early and severe rheumatoid arthritis. A role for microRNAs?
Authors: Alarcon Michele Fresneda , Abdullah Genna Ali , Beggs John Alexander , Kynoch Isobel , Sellin Andrew , Cross Andrew , Haldenby Sam , Antczak Philipp , Gutiérrez Eva Caamaño , Wright Helen Louise
Published: December 2024

Neutrophils are innate immune cells that drive the progression of rheumatoid arthritis (RA) through the release of reactive oxygen species (ROS), neutrophil extracellular traps (NETs) and proteases that damage host tissues. Neutrophil activation is regulated, in part, by dynamic changes in gene expression. In this study we have used RNAseq to measure the transcriptomes of neutrophils from people with severe, methotrexate-refractory RA and healthy controls. We identified a dynamic gene expression profile in people with severe RA. This is dominated by a type-I interferon-induced gene expression signature as well as activation of genes regulating neutrophil degranulation, NET production, response to ROS and oxidative stress. Whilst we did not detect significantly elevated levels of interferon-alpha in RA blood sera, we identified increased expression in RA neutrophils of miR-96- 5p and miR-183-5p which regulate activation of the interferon pathway as members of the miR-183C cluster. We also detected significantly elevated NET debris in RA blood sera (p<0.05). Using gene set variation analysis we explored the heterogeneity of neutrophil gene expression in RA and identified subsets of patients with gene expression profiles reflecting enhanced neutrophil degranulation and cytotoxicity, tissue inflammation or activation by interferons. Comparison with published single-cell RNAseq datasets identified RA transcriptomes where neutrophils were polarised by genes relating to early or late cell maturity, with significant genes in each polarised state being regulated by miR-146a- 5p, miR-155-5p, miR-183-5p or miR-96-5p. Overall our study demonstrates the heterogeneity of the RA neutrophil transcriptome and proposes miRNA-driven mechanisms for regulating the activated neutrophil phenotype in RA.
Closing Gaps in Evidence-Based Care for Acute Myocardial Infarction in northern Tanzania: Insights from a Prospective Study
Authors: Adisa Olanrewaju , Brown Erin E , Sakita Francis M , Temu Gloria , Rugakingira Anzibert , Lameck Godfrey , Shayo Frida M , Mmbaga Blandina T , Thielman Nathan M , Bloomfield Gerald S , Bettger Janet P , Hertz Julian T
Published: December 2024

Background

The burden of Acute Myocardial Infarction (AMI) is growing in sub-Saharan Africa. In Tanzania, uptake of diagnostic testing and evidence-based therapy for AMI is suboptimal. We aimed to describe current gaps in evidence-based AMI care in a Tanzanian emergency department (ED) and estimate the potential benefit of closing key performance gaps.

Methods

Adults presenting with chest pain or dyspnea to the Kilimanjaro Christian Medical Centre (KCMC) ED were prospectively enrolled from February to September 2023 and their diagnostic tests and treatments were recorded. Thirty days following enrollment, a follow-up telephone survey was administered to assess mortality and medication use. Key performance metrics included the proportion of participants receiving both electrocardiography (ECG) and cardiac biomarker testing, as well as the proportion of participants with AMI receiving evidence-based therapies. To estimate the benefits of closing performance gaps, the the annualized number of participants not receiving each element evidence-based therapy was divided by published numbers needed to treat (NNTs) for each intervention. An exploratory analysis was conducted using performance metrics at KCMC and published national incidence data to estimate the potential benefits of closing performance gaps in AMI care at scale across Tanzania.

Results

Of 275 enrolled participants, 41 (14.9%) met criteria for AMI. Of participants, 91 (33.1%) received both ECG and cardiac biomarker testing. Of participants with AMI, 14 (34%) received aspirin, 11 (27%) received clopidogrel, and 2 (5%) received heparin. At 30-day follow-up, 25 (61%) participants with AMI were still alive, of whom 3 (12%) were taking dual antiplatelet therapy. Closing the diagnostic gap at KCMC could lead to the identification of an estimated 121 additional AMI cases annually. Aggregate estimated total benefit for closing gaps in uptake of aspirin, clopidogrel, heparin, and dual-antiplatelet therapy would result in approximately 6 deaths prevented and 33 serious cardiovascular events prevented at KCMC annually. Closing performance gaps at scale across Tanzania would result in approximately 69,206 additional AMI cases identified, 3,003 deaths prevented, and 11,405 serious cardiovascular events prevented annually.

Conclusions

Closing diagnostic and treatment gaps in AMI care in northern Tanzania presents an opportunity to increase case identification, save lives, and prevent cardiovascular events and rehospitalizations.
COVID-19 Vaccine Acceptance and Hesitancy in Cameroon: A Systematic Review and Meta-analysis
Authors: Cheuyem Fabrice Zobel Lekeumo , Amani Adidja , Nkodo Iyawa Clarisse Alma , Boukeng Lionel Bethold Keubou , Edzamba Michel Franck , Nouko Ariane , Guissana Edwige Omona , Ngos Christelle Sandrine , Achangwa Chabeja , Mouangue Christian
Published: December 2024

Background

The development of effective vaccines was a promising tool for ending the pandemic. However, the success of a vaccination programme depends heavily on achieving significant community acceptance. In Cameroon, numerous studies have investigated the level of acceptance, hesitancy and perception of COVID-19 vaccines, with mixed results. To provide a comprehensive understanding of these parameters, this meta-analysis aimed to estimate the pooled proportion of COVID-19 vaccine acceptance, hesitancy and perception in Cameroon.

Methods

A systematic search of online databases, including PubMed, Google Scholar, and ScienceDirect, was conducted to identify relevant research articles. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The extracted data were compiled in a Microsoft Excel spreadsheet and analyzed using R statistical software (version 4.3.3). The pooled proportion of COVID-19 vaccine acceptance, hesitancy, and perception was calculated using random effects meta-analysis. Funnel plots, Egger’s and Begg’s tests were used to assess publication bias.

Results

Of the 1243 records identified through the database search, 20 research articles were included in the systematic review and meta-analysis. The random-effects model showed that the that approximately 31.21% (95% CI: 23.49-38.94) of the Cameroonian population was willing to accept the COVID-19 vaccine. More than two-thirds of the population (68.49%; 95% CI: 60.65-76.34) were vaccine hesitant. Half of the participants (51.81%; 95% CI: 42.70-60.93), had a negative perception of the COVID-19 vaccine. The acceptance rate progressed from the first semester of 2021 (27.21%; 95% CI: 10.38-44.05) to the first semester of 2022 (45.56%; 95% CI: 25-66.12). The pooled vaccine acceptance rate was 29.29% (95% CI: 19.86-38.72) for the general population and 39.24% (95% CI: 22.84-55.64) for healthcare workers. The pooled vaccine hesitancy rate was 70.39% (95% CI: 61.30-79.80) for the general population and 57.42 % (95% CI: 4.05-71.80) for healthcare workers

Conclusion

Despite progress in vaccine acceptance, targeted interventions are still needed to address vaccine hesitancy in the country. Strategies such as improving access to accurate information, building trust in institutions, and strengthening community engagement are crucial to increasing COVID-19 vaccine uptake.
Coral anthozoan-specific opsins employ a novel chloride counterion for spectral tuning
Authors: Sakai Yusuke , Sen Saumik , Sugihara Tomohiro , Kakeyama Yukiya , Iwasaki Makoto , Schertler Gebhard F.X. , Deupi Xavier , Koyanagi Mitsumasa , Terakita Akihisa
Published: December 2024

Animal opsins are G protein coupled receptors that have evolved to sense light by covalently binding a retinal chromophore via a protonated (positively charged) Schiff base. A negatively charged amino acid in the opsin, acting as a counterion, stabilises the proton on the Schiff base, which is essential for sensitivity to visible light. In this study, we investigate the spectroscopic properties of a unique class of opsins from a reef-building coral belonging to the anthozoan-specific opsin II group (ASO-II opsins), which intriguingly lack a counterion residue at any of established sites. Our findings reveal that, unlike other known animal opsins, the protonated state of the Schiff base in visible light-sensitive ASO-II opsins is highly dependent on exogenously supplied chloride ions (Cl−). By using structural modelling and QM/MM calculations to interpret spectroscopy data, we conclude that, in the dark state, ASO-II opsins employ environmental Cl−as their native counterion, while a nearby polar residue, Glu292 in its protonated neutral form, facilitates Cl−binding. In contrast, Glu292 plays a crucial role in maintaining the protonation state of the Schiff base in the light-activated protein, serving as the counterion in the photoproduct. Furthermore, Glu292 is involved in G protein activation of the ASO-II opsin, suggesting that this novel counterion system coordinates multiple functional properties.
Notch signaling stabilizes lengths of motile cilia in multiciliated cells in the lung
Authors: Joy Neenu , Deshpande Aditya , Lingamallu Sai Manoz , Prabantu Vasam Manjveekar , Naveenkumar CN , Bharathkumar K , Bhat Sukanya , Alvarado-Martinez Zabdiel , Livraghi-Butrico Alessandra , Hagood James S. , Boucher Richard C. , Lafkas Daniel , Byrd Kevin M. , Narayanan Shridhar , Shandil R.K. , Guha Arjun
Published: December 2024

Airway multiciliated cells (MCs) maintain respiratory health by clearing mucus and trapped particles through the beating of motile cilia. While it is known that ciliary lengths decrease along the proximal-distal (P-D) axis of the tracheobronchial tree, how this is regulated is unclear. Here, we demonstrate that canonical Notch signaling in MCs plays a critical role in stabilizing ciliary length. Inhibition of Notch signaling in MCs results in ciliary shortening in the trachea, lengthening in the distal airway, and to region-specific alterations in gene expression. We probe how environmental challenges impact MC homeostasis using germ-free andMycobacterium tuberculosis(M. tb) infection models. While germ-free conditions do not perturb ciliary lengths,M. tbinfection leads to lengthening of distal airway cilia, correlating with a downregulation of Notch signaling. These findings reveal that ciliary length and the P-D gradient in the airways are actively regulated, with Notch signaling serving as a stabilizing mechanism.
Mycobacterial EsxG·EsxH (TB9.8·TB10.4) peptides as a subunit vaccine to booster BCG vaccination in an experimental model of pulmonary Tuberculosis
Authors: Martínez-Olivares Constanza Estefania , Lozano-Ordaz Vasti , Mata-Espinosa Dulce , Barrios-Payán Jorge Alberto , Ortiz-Cabrera Ángel Elías , Rodríguez-Miguez Yadira Rocio , Hernández-Pando Rogelio
Published: December 2024

The attenuatedMycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine is currently the only validated vaccine against tuberculosis (TB). In a previous study, we conducted anin-silicoselection of four peptides (G1, G2, H1, and H2) derived from the mycobacterial protein antigens TB10.9·TB10.4 (EsxG·EsxH). Bioinformatic analysis and molecular dynamic simulations predicted these epitopes could be loaded into a MHC-II complex, inducing T and B cell activation. The present study aimed to experimentally validate these peptides as subunit vaccines by determining their cytotoxicity, immunogenicity, and protective efficacy againstMycobacterium tuberculosis(Mtb) in mice when administered as a booster to BCG vaccination. Mice were vaccinated with BCG and, two months later, were subcutaneously immunized with either peptide G1, G2, H1, or H2. One-month post-immunization, mice were challenged with the reference strain H37Rv of moderate virulence or the hypervirulent clinical isolate 09005186. After vaccination and before the challenge, the spleen and lung cells were harvested and stimulatedin vitrowith the corresponding peptide to measure cytokine expression in CD4+, and CD8+T cells, as well as the phenotypes of activated effector T cells, proliferative senescence, central and periphery memory CD4+and CD8+cells. Additionally, specific IgG antibody titers elicited by each peptide were measured using ELISA. Compared with animals vaccinated only with BCG, boosting BCG vaccination with these peptides provided enhanced protection by significantly prolonging the mice survival, reducing the bacillary load, and decreasing tissue damage (pneumonia). These findings contribute to the broader understanding of peptide-based subunit vaccines and highlight the potential for tailored approaches to enhance protective immunity.
SalmonellaTyphimurium Manipulates Syntaxin 7 to Navigate Endo-Lysosomal Trafficking in Host Cells
Authors: Vij Rhea , Chatterjee Ritika , Nair Abhilash Vijay , Singh Anmol , Hajra Dipasree , Gangi Setty Subba Rao , Chakravortty Dipshikha
Published: December 2024

Intracellular pathogens rely on manipulating host endocytic pathways to ensure survival.LegionellaandChlamydiaexploit host SNARE proteins, withLegionellacleaving syntaxin 17 (STX17) andChlamydiainteracting with VAMP8 and VAMP7. Similarly,Salmonellatargets the host’s endosomal fusion machinery, using SPI effectors like SipC and SipA to interact with syntaxin 6 (STX6) and syntaxin 8 (STX8), respectively, maintaining its vacuolar niche. Recent evidence highlights syntaxin 7 (STX7), a Qa-SNARE involved in endo-lysosomal fusion, as a potentialSalmonellatarget. BioID screening revealed STX7 interactions with SPI-2 effectors SifA and SopD2, suggesting a critical role inSalmonellapathogenesis. We investigated the role of STX7 inSalmonella-containing vacuole (SCV) biogenesis and pathogenesis in macrophages and epithelial cells. Our findings indicate that STX7 levels and localization differ between these cell types during infection, reflecting the distinct survival strategies ofSalmonella. Live cell imaging showed that STX7 is recruited to SCVs at different infection stages, with significantly altered distribution in HeLa cells at the late stage of infection. STX7 knockdown resulted in reduced bacterial survival, which was rescued upon overexpression of STX7 in both HeLa and RAW264.7 cells, suggestingSalmonellahijacks STX7 to evade lysosomal fusion and secure nutrients for intracellular replication. These results underscore the essential role of STX7 in maintaining SCVs and facilitatingSalmonellasurvival. Further, the temporal expression of STX7 adaptor/binding partners in macrophages showed dynamic interactions with STX7 facilitatingSalmonellainfection and survival in host cells. Together, our study highlights STX7 as a critical host factor exploited bySalmonella, providing insights into the molecular mechanisms underlying its pathogenesis in macrophages and epithelial cells. These findings may in form strategies for targeting host-pathogen interactions to combatSalmonellainfections.
A novel membrane stress-response that blocks chromosomal replication by targeting the DnaA initiator via the ClpP protease
Authors: Gbolahan Alabi , Li Tong , Saxena Rishit , Wolcott Karen , Sohail Aamna , Ahmad Ishika , Chattoraj Dhruba K. , Crooke Elliott , Saxena Rahul
Published: December 2024

InEscherichia coli, membrane-stress due to interrupted lipoprotein (Lpp) maturation impairs DNA replication and arrests cell growth. How the two disparate processes of Lpp maturation and DNA replication are connected remains unclear. We demonstrate that upon membrane-stress the Rcs stress-response pathway is activated and the replication initiator DnaA is lost, which explains the replication block. However, the Lon protease, a key regulator of the Rcs pathway, is not required for the DnaA loss. We further ruled out the involvement of (p)ppGpp, one of the major mediators of stress-response in bacteria. However, upon deletion of the ClpP protease gene, DnaA was stable, replication initiated, and there was no cell-growth arrest. In wildtype cells, overexpression of DnaA was lethal even without the membrane-stress apparently from hyper-initiation. The hyper-initiation was restrained in Δcrpcells, and overexpression of DnaA was able to overcome the growth-arrest. Δfiscells, which were earlier found resistant to the membrane-stress, showed DnaA stability and normal replication upon induction of the membrane-stress. We conclude that DnaA loss suffices to explain the growth-arrest upon the membrane-stress. The stress-response pathway described here appears novel because of its independence from Lon and (p)ppGpp, which have been implicated in other stress-responses that block DNA replication.

Significance

The seminal observation that DNA replication-stress can block cell division inE. coli(SOS response), introduced the concept of checkpoint control in the cell cycle. Here, we describe a novel checkpoint control that functions in the opposite direction: membrane-stress causing replication block. We show how two apparently unrelated outcomes of reducing a membrane phospholipid, accumulation of a precursor lipoprotein (pLpp) and block of replication initiation, could be linked. The pLpp accumulation stresses the membrane that causes a response culminating in activating the ClpP protease that blocks replication by targeting the initiator DnaA. DnaA being vital and highly conserved, the detail understanding of the response pathway is likely to open new avenues to treat bacterial infection.
Paratope mapping of tilvestamab, an anti-AXL function blocking antibody, using high-throughput bacterial expression of secreted scFv-ompY fusion proteins
Authors: Christakou Eleni , Kursula Petri , Micklem David
Published: December 2024

Targeting AXL with a highly selective antibody presents a promising approach for inhibiting AXL and potentially improving cancer treatment. An essential step in antibody optimisation is the mapping of paratope residues to epitope residues. In this study, we identify the residues of tilvestamab, a function-blocking anti-AXL monoclonal antibody (mAb), that are essential for its binding to the extracellular domain of AXL. A single-chain variable fragment (scFv) fused to osmotically inducible protein Y (osmY) was designed to enable the secretion of soluble scFv-osmY mutants, which could be directly subjected to high-throughput biolayer interferometry (BLI) screening for binding to the AXL Ig1 domain. Each CDR residue of scFv was mutated to Ala, while additional mutations were made on the basis of predicted contribution to binding. We generated Alphafold3 predictions for the scFv(tilvestamab)-AXL Ig1 complex to gain insights into the molecular interactions of the essential residues, as determined by the experimental data. Our study reveals that tilvestamab binds to the Ig1 domain of AXL, with twelve residues on scFv (tilvestamab) contributing most to binding. Glu2 near the N terminus of AXL is essential for binding. The data give a structural view into the AXL-tilvestamab complex and allow for further optimisation of the binding interface.
Genes and pathways determining flowering time variation in temperate adapted sorghum
Authors: Mangal Harshita , Linders Kyle , Turkus Jonathan , Shrestha Nikee , Long Blake , Cebert Ernst , Kuang Xianyan , Torres-Rodriguez J. Vladimir , Schnable James C.
Published: December 2024

The timing of the transition from vegetative to reproductive growth is determined by a complex genetic architecture integrating signals from a diverse set of external and internal stimuli and plays a key role in determining plant fitness and adaptation. However, significant divergence in the identities and functions of many flowering time pathway components has been reported among plant species. Here we employ a combination of genome and transcriptome wide association studies to identify genetic determinants of variation in flowering time across multiple environments in a large panel of primarily photoperiod-insensitive sorghum (Sorghum bicolor), a major crop that has, to date, been the subject of substantially less genetic investigation than its relatives. Gene families that form core components of the flowering time pathway in other species, FT-like and SOC1-like genes, appear to play similar roles in sorghum, but the genes identified are not orthologous to the primary FT-like or SOC1-like genes which play similar roles in related species. The aging pathway appears to play a significant role in determining non-photoperiod determined variation in flowering time in sorghum. Two components of this pathway were identified in a transcriptome wide association study, while a third was identified via genome wide association. Our results demonstrate that, while the functions of larger gene families are conserved, functional data from even closely related species is not a reliable guide to which gene copies will play roles in determining natural variation in flowering time.
Vacuum stability in the Standard Model and beyond
Authors: Hiller Gudrun , Höhne Tim , Litim Daniel F. , Steudtner Tom
Published: December 2024

We revisit the stability of the Standard Model vacuum and investigate its quantum effective potential using the highest available orders in perturbation theory and the most accurate determination of input parameters to date. We observe that the stability of the electroweak vacuum centrally depends on the values of the top mass and the strong coupling constant. We estimate that reducing their uncertainties by a factor of 2–3 is sufficient to establish or refute Standard Model vacuum stability at the 5σ level. We further investigate vacuum stability for a variety of singlet scalar field extensions with and without flavor using the Higgs portal mechanism. We identify the beyond Standard Model parameter spaces for stability and find sizable room for new physics. We further study the phenomenology of Planck-safe models at colliders and determine the impact on the Higgs trilinear, the Higgs-to-electroweak-boson, and the Higgs quartic couplings, some of which can be significant. The former two can be probed at the HL-LHC; the latter requires a future collider with sufficient energy and precision such as the FCC-hh.

Published by the American Physical Society
2024
Unified origin of inflation, baryon asymmetry, and neutrino mass
Authors: Kaladharan Ajay , Saad Shaikh
Published: December 2024

In this work, we present a unified theoretical framework that simultaneously addresses some of the most intriguing puzzles in particle physics and cosmology, namely the origins of neutrino mass, baryon asymmetry, and cosmic inflation. In our model, inflation is driven by a combination of the Standard Model Higgs, the type II seesaw Higgs responsible for neutrino mass generation, and the unified symmetry-breaking Higgs field. During inflation, nonzero values of the latter field ensure the absence of the monopole problem. The baryon asymmetry is generated through the Affleck-Dine mechanism, facilitated by the nonzero angular motion in the phase of a complex scalar field, which is part of the inflaton. We find that the successful parameter region for generating baryon asymmetry through a renormalizable term in the scalar potential requires a rather heavy type II seesaw triplet, with a mass well beyond the TeV scale. Inflationary observables, in particular, the spectral index is in excellent agree with experimental observation, whereas tensor-to scalar ratio is expected to be probed by the future LiteBIRD and CMB-S4 missions.

Published by the American Physical Society
2024
Generalization of the Gauss map: A jump into chaos with universal features
Authors: Beck Christian , Tirnakli Ugur , Tsallis Constantino
Published: December 2024

The Gauss map (or continued fraction map) is an important dissipative one-dimensional discrete-time dynamical system that exhibits chaotic behavior, and it generates a symbolic dynamics consisting of infinitely many different symbols. Here we introduce a generalization of the Gauss map, which is given by xt+1=1xtα−1xtα where α≥0 is a parameter and xt∈[0,1] (t=0,1,2,3,...). The symbol [⋯] denotes the integer part. This map reduces to the ordinary Gauss map for α=1. The system exhibits a sudden “jump into chaos” at the critical parameter value α=αc≡0.241485141808811⋯ which we analyze in detail in this paper. Several analytical and numerical results are established for this new map as a function of the parameter α. In particular, we show that, at the critical point, the invariant density approaches a q-Gaussian with q=2 (i.e., the Cauchy distribution), which becomes infinitely narrow as α→αc+. Moreover, in the chaotic region for large values of the parameter α we analytically derive approximate formulas for the invariant density, by solving the corresponding Perron-Frobenius equation. For α→∞ the uniform density is approached. We provide arguments that some features of this transition scenario are universal and are relevant for other, more general systems as well.

Published by the American Physical Society
2024
How does financial reporting quality mediate ESG performance to investment efficiency?
Authors: Maiyarni Reka , Utama Sidharta , Djakman Chaerul D. , Mita Aria Farah
Published: December 2024

Purpose

This study aims to assess the direct and indirect effects of environmental, social and governance (ESG) performance on investment efficiency by investigating the role of financial reporting quality in mediating this relationship.

Design/methodology/approach

To obtain a more comprehensive measurement of ESG performance, this study used both Refinitiv Eikon and Bloomberg ESG scores, while previous studies typically used one ESG score measurement. The test was conducted on cross-country samples of 5,980 observations over 2016–2023. The mediation effect was tested using the three-stage least squares method developed by Baron and Kenny (1986). The Oster test was done to address endogeneity issues that become a matter of concern in determining the estimation model used in this study.

Findings

Empirical results show that ESG performance positively affects investment efficiency, and financial reporting quality mediates the positive effects of ESG performance on investment efficiency. The results of this study indicate that ESG performance will reduce agency problems, thus increasing investment efficiency. This implies that high ESG performance and good financial reporting quality are determining factors for companies to invest more efficiently.

Originality/value

This study reveals how ESG performance affects investment efficiency mediated by financial reporting quality, which has never been discussed in other studies. ESG performance was measured by using the average of Bloomberg ESG score and Refinitiv Eikon ESG score to complement previous studies that generally used one ESG score measurement.
Ethical banking practices: a comparative analysis of Islamic and conventional banks in GCC countries
Authors: Abu ALHaija Elias , Lataifeh Amjed , Al-Haraizah Ahed , Meqdade Mohammad , Yousef Nadia
Published: December 2024

Purpose

This study aims to present insights for the preparation of ethical practices in the banking industry of gulf cooperation council (GCC) countries for profit maximization. This study presented information regarding ethical banking practices to determine to which extent banks in GCC countries practiced ethics.

Design/methodology/approach

This study followed a mixed-method approach, including both qualitative and quantitative data. For quantitative, data were collected from senior managers employed in 52 leading Islamic and conventional banks across the GCC countries, including the banks in the Kingdom of Bahrain and also from the banks in Kuwait. However, for qualitative analysis, an interview with an Islamic banking specialist was conducted.

Findings

The findings of both, qualitative and results from answer of respondents and quantitative results, that is, 91% of respondents strongly agreed that Islamic banks are more committed to ethical investments of projects, revealed that Islamic banks follow more ethical practices than conventional banks. Therefore, the mean score for EBP4 is 4.55 with moderate SD of 1.267. This statistical evidence is in favor that Islamic banks follow more ethical principles.

Research limitations/implications

Respondents were recruited randomly, and the samples consisted of only senior executives and not customers. Because of time and resource limitations, these executives were a sample of conventional and Islamic banks in the GCC only and not from other regions.

Practical implications

The results of this study provided valuable insights to conventional financial institutions, enabling them to enhance their operations as Islamic banks align with more ethical standards.

Originality/value

The research originality lies in its contribution for GCC countries by presenting a comparative view. This study defined and compared similarities and differences of Islamic and conventional banks to indicate how Islamic banks particularly implement more ethical standards than conventional banks.
An overview of the expected public values arising from blockchain adoption in the European public sector
Authors: Rodriguez Müller A. Paula , Martin Bosch Jaume , Tangi Luca
Published: December 2024

Purpose

This study aims to systematically explore the anticipated realisation of public values through blockchain technology (BCT) within the European public sector. Its purpose is to offer a comprehensive analysis of BCT implementations, focusing on the various expected public values and understanding how these expectations shape the adoption of BCT in public administration across Europe.

Design/methodology/approach

This research involves a qualitative analysis of 165 BCT use cases across European governments at the national, regional and local levels. The study employs a public values lens, categorising the expected public values into three clusters: internal, external and relational.

Findings

The results indicate that most cases focus on external transformation, aiming to improve public service provision and enhance citizen satisfaction and engagement by increasing public trust, efficiency, accountability and transparency. For the internal dimension, the results emphasise security, efficiency and cooperativeness as expected public values in adopting BCT. Finally, fewer cases highlight expectations related to relational public values, such as citizen involvement and democratic participation.

Originality/value

This research offers new insights into BCT in the public sector through a public values lens within the European context. It examines the expected public values arising from BCT adoption, providing insights for policymakers and practitioners considering BCT integration in daily operations. This study emphasises the need for further empirical research to explore BCT’s potential in realising these expected public values and to evaluate the trade-offs and disruptive impacts on public administrations.
Dynamic characteristics of hybrid water-lubricated herringbone groove journal bearing
Authors: Xu Ge , Jiang Shuyun , Zhang Chibin , Lin Xiaohui
Published: December 2024

Purpose

The water-lubricated hydrodynamic herringbone groove journal bearing (HGJB) is capable of running at high speed. However, when running at a low speed, it suffers from a low load-carrying capacity due to the weak hydrodynamic effect. To overcome this problem, this study proposes a hybrid water-lubricated HGJB and aims to investigate its dynamic characteristics.

Design/methodology/approach

A hybrid lubrication model applicable to the hybrid water-lubricated HGJB is established based on the boundary fitted coordinate system, which considers the turbulent, thermal and tilting effects, and the finite difference method is used to calculate the dynamic characteristics of the hybrid water-lubricated HGJB.

Findings

The result shows that the hybrid HGJB has larger dynamic coefficients and better system stability compared with the hydrodynamic HGJB when running at low speed. Furthermore, the stiffness of hybrid HGJB are mainly governed by the hydrodynamic effect rather than the hydrostatic effect when running at high speed.

Originality/value

The proposed hybrid water-lubricated HGJB shows excellent dynamic characteristics at either low speed or high speed; and the hybrid water-lubricated HGJB has a large load-carrying capacity when running at low speed and has a good dynamic stability when running at high speed.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-06-2024-0233/
Expected cross-sectional stock return idiosyncratic volatility and stock delistings
Authors: Khovansky Serguey , Zhylyevskyy Oleksandr
Published: December 2024

Purpose

We estimate expected cross-sectional idiosyncratic stock return volatility (expected IVOL), explore its dynamics and attempt to link it to the characteristics related to the real economy.

Design/methodology/approach

We estimate expected cross-sectional idiosyncratic stock return volatility at the annual frequency in the setting of an Inter-temporal Capital Asset Pricing Model model by applying a Generalized Method of Moments with a Common Shock.

Findings

We find that the number of stock issues delisted from exchanges have a significant effect on expected IVOL. The discovered relationship is robust to controlling for aggregate financial and economic variables previously found in the literature to contribute to average IVOL.

Originality/value

Our empirical findings are supported by a formal model. Firms’ stock delistings are mainly associated with mergers and stock drops, which effect on expected IVOL (across the firms’ surviving rivals) and is explained in the context of Bayesian Cournot-Nash equilibrium.
Price risk transfer from futures to spot prices in energy commodities: measuring the effects of the Covid-19 pandemic and of the Russo–Ukrainian conflict
Authors: Panagiotou Dimitrios , Karamanis Konstantinos
Published: December 2024

Purpose

The purpose of this paper is to measure price risk transfer from futures prices to spot prices in the markets of energy commodities.

Design/methodology/approach

To this end, it estimates CoVaR functions for five futures-spot prices pairs of energy commodities. To account for the effects of the Covid-19 pandemic as well as for the effects of the Russo−Ukrainian conflict, the total sample has been split into three sub-samples. The first one contains observations from 01/01/2010–3/11/2020, which marks the official declaration of the coronavirus as a global pandemic. The second sub-sample uses observations from 3/12/2020–2/24/2022, which marks the beginning of the Russo−Ukrainian conflict, and the third one includes observations from 2/25/2022 up to 8/31/2023.

Findings

Results indicate that the effect of the coronavirus pandemic was to increase the risk of price transfer from futures markets to spot markets, in all of the energy commodities examined. On the other hand, the effect of the escalation of the Russo−Ukrainian conflict was to significantly reduce the price risk transfer from the futures markets to the spot markets, in all five energy commodities.

Originality/value

To the best of the authors’ knowledge, this is the first study to use CoVaR functions to estimate risk transfer among the energy commodities. In addition, it separates and estimates the effects of the Covid-19 pandemic as well as the effects of the Russo−Ukrainian conflict.
Discrete choice modelling of willingness to pay for facility retrofitting: a multinomial logit model approach
Authors: Aguome Njideka Maryclara , Ewurum Nonso Izuchukwu , Emoh Fidelis Ifeanyi
Published: December 2024

Purpose

The global imperative for sustainable infrastructure management has intensified the focus on facility retrofitting as a key strategy for reducing environmental impact and enhancing operational efficiency. However, the complex interplay of factors influencing stakeholders’ willingness to pay (WTP) for such interventions remains inadequately understood, impeding effective policy formulation and resource allocation. This study aims to examine the motivational factors influencing the adoption of green retrofits in Lagos, Nigeria.

Design/methodology/approach

This study used a stated preference discrete choice experiment conducted with 425 decision-makers of corporate facilities in Lagos, Nigeria. A multinomial logit model was used to compare retrofitting choice sets and a status quo option.

Findings

The study revealed that education level, reputation concerns, income, incentives and corporate social responsibility awareness significantly predicted WTP for basic heating ventilation air-conditioning, and lighting upgrades. Regulatory compliance, awareness, education, income and reputation emerged as key drivers for more comprehensive retrofits incorporating renewables.

Practical implications

The research findings, by revealing which motivators resonate strongest, offer an evidence-based roadmap that directs practitioners to look beyond price incentives and emphasize complementary non-price interventions integrated with policy. The study’s emphasis on the significance of noneconomic WTP drivers equips program administrators with actionable strategies to optimize the uptake of retrofits based on individuals’ motivational structures.

Originality/value

This is one of the very few studies that have investigated the motivational factors influencing the adoption of green facility retrofitting in emerging markets, focusing on Lagos, Nigeria.