bluuebunny/crossref_metadata_2025 huggingface dataset:
Yeast DNA Polymerase δ Proofreading Nuclease Suppresses Translesion Synthesis and Facilitates Recombination in DNA Lesion Bypass
Authors: Che Jun , Wang Quan , He Jiapeng , Zhang Zhao , Chung Jee Min , Gallagher Danielle N. , Hong Xin , Rao Hai , Shim Eun , Haber James E. , Niu Hengyao , Lee Sang Eun
Published: January 2025

Translesion synthesis (TLS) employs specialized polymerases to incorporate nucleotides opposite DNA lesions, allowing replication to continue temporarily without repairing the lesions, while sacrificing replication fidelity (1). TLS depends on a ubiquitin molecule attached to the clamp PCNA at residue Lys164(2, 3); the precise biochemical and molecular basis how PCNA modification stimulates TLS is still elusive (4-10). In this study, we discovered that DNA polymerase δ (Pol δ) 3’ to 5’ “proofreading” exonuclease degrades nascent TLS synthesis opposite pyrimidine dimers and inhibits TLS on both leading and lagging strands. Rad18 E3 ligase and PCNA ubiquitylation become dispensable for TLS when Pol δ exonuclease is inactive. Biochemical reconstitution showed that the major UV lesion bypass polymerase Rad30 is intrinsically inefficient at bypassing thymidine dimers and requires multiple turnovers. Pol δ exonuclease impedes Rad30 activity both catalytically and non-catalytically during and post-lesion bypass. Importantly, PCNA and PCNA ubiquitylation enhance processivity of Rad30 after thymidine dimer bypass, a critical step for further DNA synthesis extension and overcoming Pol δ inhibition. Our study reveals a new paradigm how PCNA ubiquitylation facilitates TLS and the new role of Pol δ nuclease in lesion bypass pathway choice and replication fidelity at fork-blocking DNA lesions.
Exploring the Pathogen Profiles of Ancient Feces
Authors: Capone Drew , Holcomb David , Lai Amanda , Reinhard Karl , Brown Joe
Published: January 2025

Analysis of ancient desiccated feces – termed paleofeces or coprolites – can unlock insights into the lives of ancient people. We collected desiccated feces from caves in the Rio Zape Valley in Mexico (725-920 CE). First, we extracted DNA with methods previously optimized for paleofeces. Then, we applied highly sensitive modern molecular tools (i.e., PCR pre-amplification followed by multi-parallel qPCR) to assess the presence of 30 enteric pathogens. We detected ≥1 pathogen associated gene in each of the ten samples and a mean of 3.9 pathogens per sample. The targets detected includedBlastocystisspp. (n=7), atypical enteropathogenicE. coli(n=7),Enterobius vermicularis(n=6),Entamoebaspp. (n=5), enterotoxigenicE. coli(n=5),Shigellaspp./enteroinvasiveE. coli(n=3),Giardiaspp. (n=2), andE. coliO157:H7 (n=1). The protozoan pathogens we detected (i.e.,Giardiaspp. andEntamoebaspp.) have been previously detected in paleofeces via enzyme-linked immunoassay (ELISA), but have not via PCR. This work represents the first detection ofBlastocystisspp. atypical enteropathogenicE. coli, enterotoxigenicE. coli, Shigellaspp./enteroinvasiveE. coli, andE. coliO157:H7 in paleofeces. These results suggest that sensitive modern molecular tools, such as PCR, can be used to evaluate ancient materials for genes of interest.
Deciphering the Host-Pathogen Interface in COVID-19: The precision molecular insight into epitranscriptomic modifications of high-impact transcripts
Authors: Maździarz Mateusz , Krawczyk Katarzyna , Lepiarczyk Ewa , Paukszto Łukasz , Makowczenko Karol G. , Moczulska Beata , Iwanowicz Piotr , Kocbach Piotr , Sawicki Jakub , Gromadziński Leszek , Majewska Marta
Published: January 2025

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact since its emergence in late 2019. Characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to severe respiratory distress and death, COVID-19 has necessitated extensive research into the host-pathogen interactions that drive disease progression. Understanding the molecular mechanisms underlying the host response to SARS-CoV-2 infection is crucial for the development of effective therapeutic interventions and preventative strategies. This study employed a multi-omic approach that combined direct RNA sequencing (DRS) and Illumina cDNA sequencing to investigate whole blood transcriptomic profiles in COVID-19 patients. By leveraging the unique capabilities of Nanopore DRS, which provides long-read sequencing data, we were able to capture not only gene expression levels but also crucial RNA modifications, including poly(A) tail length, non-adenine residue (non-A), pseudouridylation (psU), and 5-methylcytosine (m5C) methylation. This comprehensive analysis allowed us to identify differentially expressed genes (DEGs) and explore the impact of these RNA modifications on gene expression and function within the context of COVID-19. Our findings reveal significant alterations in gene expression patterns, poly(A) tail lengths, non-A and the prevalence of psU and m5C modifications in COVID-19 patients compared to healthy controls. These results provide valuable insights into the complex interplay between viral infection, host immune response, and RNA processing, contributing to a deeper understanding of COVID-19 pathogenesis.
Deciphering landscape-scale plant cover and biodiversity from soil eDNA
Authors: Goodall Tim , Griffiths Robert I. , Gweon Hyun S. , Norton Lisa , Busi Susheel Bhanu , Read Daniel S.
Published: January 2025

Biodiversity surveys are critical for detecting environmental change; however, undertaking them at scale and capturing all available diversity through observation is challenging and costly. This study evaluated the potential of soil-extracted eDNA to describe plant communities and compared these findings to traditional, observation-based, field surveys. We analysed 789 soil samples using high-throughput amplicon sequencing and compared DNA-based diversity metrics, indicator taxa, predicted vegetation class, and plant cover in a comparison with co-located field survey data. The results indicated that taxonomically aggregated (genus) eDNA-derived data, while showing slightly reduced Shannon’s diversity scores, yielded remarkably similar overall richness and composition estimates. However, the DNA indicator taxa and predictive power for vegetation community classification were also lower overall than those recorded by the field survey. However, in many cases plant cover could be inferred from amplicon abundance data with some accuracy despite widely differing scales of sampling – 0.25 g crumb of soil versus a 1 m2quadrat. Overall, results from eDNA demonstrated lower sensitivity but were broadly in accordance with traditional surveys, with our findings revealing comparable taxonomic resolution at the genus level. We demonstrate the potential and limitations of a simple molecular method to inform landscape-scale plant biodiversity surveys, a vital tool in the monitoring of land use and environmental change.
Convergent molecular evolution associated with repeated transitions to gregarious larval behaviour in Heliconiini
Authors: Cicconardi Francesco , McLellan Callum F. , Seguret Alice , McMillan W. Owen , Montgomery Stephen H.
Published: January 2025

Collective behaviour forms the basis for many anti-predator strategies. Within Lepidoptera, larval gregariousness has evolved convergently across many phylogenetically disparate lineages. While the selection pressures shaping variation in larval social behaviours are well investigated, much less is known about the mechanisms that control social attraction and behavioural coordination. Similarly, little is known about how secondary selection pressures associated with social living shape genome evolution. Here, using genomic data for over 60 species from an adaptive radiation of Neotropical butterflies, the Heliconiini, in which gregarious behaviour has evolved repeatedly, we explore the molecular basis of repeated convergent shifts towards gregarious larvae. We focus on three main areas of genomic evolution: differential selection on homologous genes, accelerated rates of evolution on non-coding regions of key genes, and differential gene expression in the brains of solitary and gregarious larvae. We identify strong signatures of convergent molecular evolution, on both coding and non-coding loci, in Heliconiini lineages which evolved gregarious behaviour. Molecular convergence is also detected at the transcriptomic level in larval brains, suggesting convergent shifts in gene regulation in neural tissue. Among loci showing strong signals of convergent evolution in gregarious lineages, we identify several strong candidates linked to neural activity, feeding behaviour, and immune pathways. Our results suggest sociality profoundly changes the selection pressures acting on multiple physiological, immunological and behavioural traits.
A Simple, Low-Cost, and Efficient Protocol for Rapid Isolation of Pathogenic Bacteria from Human Blood
Authors: Coskun Fatma S. , Quick Joshua , Toprak Erdal
Published: January 2025

Bacteremia is a serious clinical condition in which pathogenic bacteria enter the bloodstream, putting patients at risk of septic shock and necessitating antibiotic treatment. Choosing the most effective antibiotic is crucial not only for resolving the infection but also for minimizing side effects, such as dysbiosis in the healthy microbiome and reducing the selection pressure for antibiotic resistance. This requires prompt identification of the pathogen and antibiotic susceptibility testing, yet these processes are inherently slow in standard clinical microbiology labs due to reliance on growth-based assays. Although alternative methods exist, they are rarely adopted in clinical settings because they involve complex protocols and high costs for training and infrastructure. Here, we present an optimized, simple protocol for rapidly and efficiently isolating bacterial pathogens from blood without altering typical laboratory workflows. Our method is cost-effective and compatible with commonly available laboratory instruments, offering the advantage of isolating bacterial cells directly, which bypasses the delays associated with traditional blood culture methods and enables faster diagnostic results. The protocol achieved over 70% efficiency within 30 minutes, remained effective at low bacterial concentrations (1–10 bacteria/0.3 mL blood), and preserved bacterial viability with no notable change in growth lag times. We validated the protocol on several clinically relevant bacterial strains, includingEscherichia coli, Klebsiella pneumoniae, andStaphylococcus aureus. These findings highlight our protocol’s potential utility in clinical and research settings, facilitating timely cultures and minimizing diagnostic delays.
Resetting public adherence: iterative strategies to counteract pandemic fatigue
Authors: Rikani Albano , Di Domenico Laura , Sabbatini Chiara E. , Navarro Victor , Ferres Leo , Raude Jocelyn , Colizza Vittoria
Published: January 2025

Non-pharmaceutical interventions (NPIs) are essential for controlling infectious diseases during pre-vaccine periods, yet their success hinges on sustained public adherence. This study investigates adherence dynamics to tiered restriction systems implemented during COVID-19 in six geographical regions across Europe, North America, Africa, and South America. Using daily mobility data and linear-mixed models, we assessed three types of fatigue: overall fatigue (linked to cumulative time under restrictions), tier fatigue (linked to time spent under a specific tier), and iteration fatigue (linked to repeated implementation of the same tier). Tier fatigue caused the most rapid adherence loss, producing effects within days that overall fatigue required months of restrictions to achieve. Iterative application of shorter NPIs, interspersed with temporary relaxation, helped reset adherence, mitigating fatigue and sometimes even improving compliance. Psychological relief and a sense of regained autonomy during relaxation periods may renew public willingness to comply when restrictions are reintroduced. These findings emphasize the dual benefits of short, strategic NPIs for epidemic control and public resilience, offering actionable insights for designing more sustainable pandemic interventions.
The effects of antibiotic prescribing for respiratory tract infection on future consultations in primary care: a systematic review and meta-analysis
Authors: Adamu Ibrahim , Lambert Amanda , Bello Safiyya , Abdulmalik Fatima Aminu , Marshall Tom
Published: January 2025

Objectives

Prescribing antibiotics may reinforce patients’ beliefs antibiotics are needed and increase future consultations for similar symptoms. This review determines the effect of antibiotic prescribing for respiratory infections in primary care on future reattendance.

Design, setting and participants

A systematic review and meta-analysis of randomised controlled trials and cohort studies, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Participants were adults or children presenting with respiratory infection in primary care.

Interventions

Prescription of antibiotics.

Primary outcome measure

Reattendance at least 28 days after initial consultation.

Method

Eligible studies included open-label randomised controlled trials (RCT) or cohort studies of antibiotics compared to no antibiotics in adults or children with respiratory infections. MEDLINE (Ovid), PubMed, Embase, the Cochrane Central Register of Controlled Trials, clinical trial registries and grey literature sources were searched from inception until 6thFebruary 2024. Two reviewers independently screened, selected, assessed quality and extracted data. Separate meta-analyses were presented for RCT and cohort studies.

Results

We identified 2128 records and reviewed 48 full texts, of which five met inclusion criteria. These reported three RCTs (1207 randomised to antibiotics, 672 controls) and three cohort studies (209,138 exposed to antibiotics, 46,469 controls). In the meta-analysis of randomised trials, relative risk (RR) of reattendance with antibiotics was 1.10 (95%CI: 0.99 to 1.23) and in the cohort studies RR was 1.21 (95%CI: 0.94 to 1.49). An important limitation is that most studies were in UK primary care.

Conclusion

Evidence suggests prescribing antibiotics for acute respiratory tract infections in primary care probably modestly increases future reattendance for similar conditions. Reducing antibiotic prescribing may help reduce demand for primary care.

PROSPERO registration number

CRD42023470731

Article summary

This systematic review of antibiotic prescribing for uncomplicated upper respiratory tract infections finds that antibiotics probably increase future consultations.

Strengths and limitations

This is the first systematic review of the effects of antibiotic prescribing for upper respiratory tract infections.

The finding that antibiotic prescribing increases future consultations for upper respiratory tract infections is consistent with other evidence.

The effect just fails to meet statistical significance.

Almost all the studies were undertaken in the UK, which may limit the generalisability.
DNA-encoded Library Screening Uncovers Potent DNMT2 Inhibitors Targeting a Cryptic Allosteric Binding Site
Authors: Frey Ariane F. , Schwan Merlin , Weldert Annabelle C. , Kadenbach Valerie , Kopp Jürgen , Nidoieva Zarina , Zimmermann Robert A. , Gleue Lukas , Zimmer Collin , Jörg Marko , Friedland Kristina , Helm Mark , Sinning Irmgard , Barthels Fabian
Published: January 2025

The human RNA methyltransferase DNMT2 is thought to be involved in various pathophysiological processes, yet, a major challenge in drug targeting DNMT2 is given by the fact that current SAH-derived inhibitors have poor target selectivity and limited cellular permeability. In this study, we have performed a DNA-encoded library (DEL) screening on DNMT2 yielding five non-SAH-like hit structures, three of which feature a peptidomimetic scaffold. All DEL hits could be validated by orthogonal biophysical and biochemical assays for DNMT2 binding. At the same time, the lead structure did not interact with related methyltransferases from the DNMT and NSUN families highlighting an unmatched DNMT2-targeting selectivity profile. Subsequent crystallographic studies revealed the unique ligand binding mode including an active site loop rearrangement and the formation of a cryptic allosteric binding pocket able to modulate the enzymatic activity by non-covalent DNMT2 dimerization. Based on the crystallographic results, we performed a structure-activity relationship study around the inhibitor lead structure resulting in an optimized DNMT2 inhibitor (KD=3.04 µM), which was able to reduce m5C levels in MOLM-13 tRNA.

GRAPHICAL ABSTRACT
m3C is a mitochondrial mRNA modification which promotes tumor progression
Authors: Penning Audrey , Wang Kun , Célérier Margot , Collignon Evelyne , Primac Irina , Van der Linden Louis , Bizet Martin , Calonne Emilie , Hassabi Bouchra , Hubert Céline , Putmans Pascale , Murisier Frédéric , Larbanoix Lionel , Achouri Younes , Lan Jie , Nemazanyy Ivan , Laurent Sophie , Jacquemin Patrick , Yi Chengqi , Deplus Rachel , Fuks François
Published: January 2025

Mitochondrial mRNA modifications are suggested to play a role in fine-tuning mitochondrial gene expression and function. However, the epitranscriptomic landscape of mitochondrial mRNA (mt-mRNA) remains poorly explored. Here, we uncover N3-methylcytosine (m3C) as a novel mt-mRNA that is catalyzed by METTL8, an enzyme previously known to modify mt-tRNA. Transcriptome-wide mapping reveals that METTL8-dependent m3C is enriched in mt-mRNAs encoding complex I subunits of the respiratory chain. Additionally, METTL8 is highly expressed in various cancers, notably in cervical cancer. METTL8 depletion impairs cell migrationin vitroand reduces tumor growth in mouse xenografts. Finally, transcriptomic analyses further link METTL8 expression to oncogenic pathways, mitochondrial functions and complex I activity. Together, our results reveal a novel mitochondrial mRNA modification that promotes cancer progression.
Identifying memory gene expression from single sample scRNA-seq data using power law signatures
Authors: Ghosh Suvranil , Chakrabarti Shaon , Raju Archishman
Published: January 2025

1

Genes with expression levels that fluctuate on time scales longer than cell division times are associated with cancer drug tolerance. However, current methods for identifying such ‘memory’ genes rely on variants of the Luria-Delbrück experiment and require either multiple replicates or lineage information, limiting their use to model systems orin-vitrosettings. We develop a new conceptual approach using recent results in Random Matrix Theory to demonstrate that the existence of memory genes results in a power-law signature in the cell covariance matrix eigenspectrum. Utilizing this theoretical framework, we develop Power-Seek, an algorithm to discover memory genes from a single time point scRNA-seq dataset. Without using prior information on lineages or cell-cycle times, Power-Seek correctly identifies memory genes in a melanoma cell line. Our results open up the possibility of identifying expression states driving drug tolerance in real-world scenarios, as we demonstrate using data from a human breast cancer tissue sample.
The histone modification regulator, SIN3, plays a role in the cellular response to changes in glycolytic flux
Authors: Soukar Imad , Mitra Anindita , Vo Linh , Rofoo Melanie , Greenberg Miriam L. , Pile Lori A.
Published: January 2025

Epigenetic regulation and metabolism are connected. Epigenetic regulators, like the SIN3 complex, affect the expression of a wide range of genes, including those encoding metabolic enzymes essential for central carbon metabolism. The idea that epigenetic modifiers can sense and respond to metabolic flux by regulating gene expression has long been proposed. In support of this cross-talk, we provide data linking SIN3 regulatory action on a subset of metabolic genes with the cellular response to changes in metabolic flux. Furthermore, we show that loss of SIN3 is linked to decreases in mitochondrial respiration and the cellular response to mitochondrial and glycolytic stress. Data presented here provide evidence that SIN3 is important for the cellular response to metabolic flux change.
Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation
Authors: Weagley James , Makimaa Heyde , Cárdenas Luis Alberto Chica , Romani Ana , Sullender Meagan , Aggarwal Somya , Hogarty Michael , Rodgers Rachel , Kennedy Elizabeth , Foster Lynne , Schriefer Lawrence A. , Baldridge Megan T.
Published: January 2025

Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored microbial populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.
ER-associated degradation relying on protein O-mannosylation
Authors: Lemus Leticia , Meyer Hadar , Rodriguez Ana , Schuldiner Maya , Goder Veit
Published: January 2025

Protein quality control in the secretory pathway, whose dysfunction is linked to various human diseases, begins in the endoplasmic reticulum (ER) and involves ER-associated degradation (ERAD) of terminally misfolded species. We have addressed the roles of protein O-mannosylation in ERAD using complementary genome-wide screens in yeast. Our findings reveal that protein O-mannosylation by the conserved ER-resident O-mannosyltransferase complex Pbn1-Gpi14 generates ERAD cues. This mechanism participates in regulating ERAD of substrates that contain serine-rich regions and provides a fail-safe mechanism for the degradation of non-N-glycosylated misfolded proteins. Our data suggest that thede novosynthesis of ERAD cues through protein O-mannosylation is an essential component of ER quality control.
Defining the networks that connect RNase III and RNase J-mediated regulation of primary and specialized metabolism inStreptomyces venezuelae
Authors: Pepler Meghan A.D. , Mulholland Emma L. , Montague Freddie R. , Elliot Marie A.
Published: January 2025

RNA metabolism involves coordinating RNA synthesis with RNA processing and degradation. Ribonucleases play fundamental roles within the cell, contributing to the cleavage, modification, and degradation of RNA molecules, with these actions ensuring appropriate gene regulation and cellular homeostasis. Here, we employed RNA-sequencing to explore the impact of RNase III and RNase J on the transcriptome ofStreptomyces venezuelae. Differential expression analysis comparing wild type and RNase mutant strains at distinct developmental stages revealed significant changes in transcript abundance, particularly in pathways related to multicellular development, nutrient acquisition, and specialized metabolism. Both RNase mutants exhibited dysregulation of the BldD regulon, including altered expression of many cyclic-di-GMP-associated enzymes. We also observed precocious chloramphenicol production in these RNase mutants and found that in the RNase III mutant, this was associated with PhoP-mediated regulation. We further found that RNase III directly targeted members of the PhoP regulon, suggesting a link between RNA metabolism and a regulator that bridges primary and specialized metabolism. We connected RNase J function with translation through the observation that RNase J directly targets multiple ribosomal protein transcripts for degradation. These findings establish distinct, but complementary roles for RNase III and RNase J in coordinating the gene expression dynamics critical forS. venezuelaedevelopment and specialized metabolism.
Development of a replication competent murine norovirus reporter system
Authors: Olson Mikayla C. , Orchard Robert C.
Published: January 2025

Caliciviruses are significant agricultural and human pathogens that are poorly understood due to the dearth of molecular tools, including reporter systems. We report the development of a stable, faithful, and robust luciferase-based reporter system for a model calicivirus, murine norovirus (MNoV). Genetic insertion of a HiBiT tag, an 11 amino acid fragment of nanolucifersase, at the junction of the nonstructural proteins NS4 and NS5 yields infectious virus. The resultant MNoV-HiBiT produces robust signal that is detected early in infection and occurs only in cells susceptible to MNoV infection. As proof of principle, we used this tool to characterize two unappreciated host directed anti-MNoV compounds. The use of the MNoV-HiBiT virus enables new mechanistic studies by a rapid and quantitative means of measuring MNoV replication. Furthermore, the HiBiT insertion strategy we describe may be useful for the generation of other calicivirus reporters.

Author Summary

Colloquially known as “the stomach bug,” human norovirus is a leading cause of foodborne illness worldwide. Despite its prevalence, there are no approved therapeutics or vaccines against norovirus owing to the challenges in cultivation of the virus and a lack of a small animal model of human norovirus. Murine Norovirus (MNoV) has emerged as a tractable model due to its similarity to human norovirus and the ability to grow the virus in laboratory strains of mice and immortalized cells in vitro. Reporter viruses, which include enzymatic or fluorescent reporter genes in the viral genome, are invaluable tools that expedite viral research. Unfortunately, there are no MNoV reporter systems available. Here we developed a novel reporter MNoV using a complimentary nanoluciferase. Specifically, we inserted a HiBiT tag into the MNoV genome that is functionalized into a full nanoluciferase protein and emits light in the presence of LgBiT. We demonstrated that MNoV-HiBiT is a faithful and sensitive reporter of viral replication across MNoV strains and cell types. We used the reporter virus to screen novel anti-viral compounds, demonstrating that the MNoV-HiBiT system is a powerful tool to enhance norovirus research.
High-Resolution Structures of Tobacco Mosaic Virus Disks from Cryo-Electron Microscopy
Authors: Abu-Baker Ismael , Biela Artur P. , Shah Sachin N. , Heddle Jonathan G. , Lomonossoff George P. , Blum Amy Szuchmacher
Published: January 2025

Tobacco mosaic virus has been involved in many important developments in virology, structural biology, and biotechnology. Despite decades of study, several key aspects of the viral assembly mechanism remain unclear, particularly the structure of the coat protein disk that initiates virus assembly by interacting with the viral RNA. Here we report the first cryo-electron microscopy structures of the coat protein disk under conditions typically used forin vitrovirus assembly. We identify 1-, 2-, and 3-layered disks, all of which differ significantly from previous structures obtained by X-ray crystallography. These new models lead to a revised viral assembly mechanism. We also compare coat proteins produced in bacteria and plants to better understand the effect of N-terminal acetylation.
Current gaps in survey design and analysis for molecular xenomonitoring of vector-borne neglected tropical diseases: a systematic review
Authors: McLure Angus , Alamnia Tilahun , Xu Zhiwei , Lau Colleen L. , Mayfield Helen J.
Published: January 2025

Objectives

Molecular Xenomonitoring (MX) is a surveillance method for vector-borne diseases where vectors are tested for molecular pathogen markers. Testing is typically on pools (groups) of vectors. MX is a sensitive and efficient complement to human based surveillance. However, there is limited guidance about the appropriate design and analysis of MX surveys. We reviewed the literature to understand the common objectives, survey designs, and analysis methods for MX surveys for two vector-borne neglected tropical diseases: lymphatic filariasis (LF) and onchocerciasis.

Methods

We searched peer-reviewed literature for studies published between 1999 and 2022 that presented the results of surveys that collected vectors in field surveys and used a molecular test for the presence of the causative pathogens for LF and onchocerciasis.

Results

A total of 76 studies (LF: 45; onchocerciasis: 31) across 30 countries were included in the review. The five most common objectives were determination of elimination status after mass drug administration, comparison of vector and human infection indicators, evaluation of an intervention, comparison of vector collection methods, and comparison of laboratory techniques. Nearly all studies used a cluster or hierarchical sampling frame to collect vectors (72/76), but very few studies accounted for this in their designs (2/76) or analysis (1/76). While few studies justified the number of vectors included in each pool (5/76), nearly all studies accounted for pooled testing when calculating pathogen prevalence from results (69/76). Few studies justified the number or selection of sampling sites or total sample size (16/76).

Conclusions

Published MX surveys for LF and onchocerciasis had varied objectives, study designs and analysis methods, but proper consideration of survey design was frequently missing from the analysis. There is a need for statistical tools and guidance to enable appropriate design and analysis of MX surveys while accounting for disease, objective, and context-specific considerations.
“Boats need water and tigers need jungle” - Locally constructed corporate social responsibility in Thailand
Authors: Kuasirikun Nooch , Constable Philip
Published: January 2025

Purpose

This paper explores corporate social responsibility (CSR) in Thailand and analyses how CSR practice is informed by local values rather than merely driven by CSR practices designed in developed countries.

Design/methodology/approach

The analysis is based on a comparative series of interviews of Thai business leaders in 2009–10 and 2019–20 within the conceptual context of Thai CSR discourse/practice, especially Buddhist Economics.

Findings

This paper argues that CSR practice in Thailand is substantially informed by local socio-economic context, particularly Buddhist Economics, including the concepts of suffering (dukkha), the Eightfold Path of the Middle Way, and gifting and reciprocal exchange.

Research limitations/implications

Local contexts are crucial not only for understanding local models of CSR but also for challenging what has been perceived as an imperialistic neo-liberal agenda in western-originating CSR.

Practical implications

The wider practical implications of this paper are that, like Thailand, CSR practices in other developing economies and emerging markets (DEEMs) may also have their own distinctive ‘local’ origins, contexts and developments which need to be considered.

Social implications

The social implications of this paper are that local context is determinant in the development of CSR practice, especially in DEEMs.

Originality/value

This paper contributes to the CSR literature by highlighting the often-marginalised existence of local CSR context and practice in DEEMs and questions CSR based solely on western theorisations.
A matrixed nonlinear grey Bernoulli model for interval number prediction of power generation in East China
Authors: Zeng Linglai , Gao Mingyun , Cang Haoze
Published: January 2025

Purpose

The interval number prediction of power generation can provide a reference for the rational planning of the power system. For the nonlinearity, uncertainty and complex trends of power generation in East China, a matrixed nonlinear grey Bernoulli model combined with the weighted conformable fractional accumulation generating operator (MWCFNGBM(1,1,tα)) is proposed.

Design/methodology/approach

First, the original sequence fluctuations are smoothed with the weighted conformable fractional accumulation generating operator. The time power term is introduced into the nonlinear grey Bernoulli model to enhance the flexibility and adaptability of predicting nonlinear and complex sequences. The model parameters are further matrixed so that the interval number sequences can be modeled directly. The improved MPA is chosen to optimize the nonlinear parameters through the algorithm comparison. Finally, the Cramer rule is used to derive the time recursive formula.

Findings

The validity and superiority of the MWCFNGBM(1,1,tα) is verified by the model comparison experiment. The total power generation in East China is predicted and analyzed from 2024 to 2027. The prediction shows that it will grow steadily over the next four years.

Originality/value

The trend of power generation in East China is complex in the short term. It is of research significance to use the grey model for short-term interval prediction of power generation. For the data characteristics of power generation, a grey interval number prediction model for power generation prediction is proposed.
Exploring co-participation in health: strategies and initiatives towards inclusive well-being
Authors: Traub Carolina , Kovacevic Rialda
Published: January 2025

Purpose

This article explores the main elements of co-participation in health, examining how community engagement can improve health outcomes and health services’ overall efficiency. It aims to discuss and identify key features that facilitate co-participation strategies in service delivery and health program implementation.

Design/methodology/approach

The authors conducted a general literature review to comprehensively explore the role of co-participation in health, drawing on scientific literature and real-world examples to identify key factors that contribute to successful health interventions. A total of 50 published resources were included, and a descriptive analysis was performed, focusing on summarizing existing literature and highlighting key themes and practical strategies. Documents were selected from publications dated between 2004 and 2024.

Findings

Community participation is presented as a critical factor in improving population health outcomes. The examined initiatives promote the idea that community integration into the design and implementation of health programs increases treatment adherence, users' health perception and improved health outcomes. Several strategies and approaches are presented as key tools to adequately integrate community engagement such as community empowerment, government decentralization and incorporation of technology, among others.

Practical implications

Coparticipation in health improves health outcomes and promotes greater equity and social justice. Involving citizens in health decision-making contributes to improving the quality of life and well-being of the community. Empowering patients’ decision-making not only builds one’s self-agency in health decision-making but also simultaneously facilitates closing the gaps in healthcare service delivery due to large shortages in the health workforce around the world. This has further implications for overall health systems’ financing, efficiency and sustainability.

Social implications

This research has social implications as it underscores how community participation is essential for fostering equity, justice and inclusivity within health systems.

Originality/value

This article offers an innovative perspective on the role of partnership in achieving good health outcomes, highlighting the importance of adapting interventions to local contexts, the need for sustainable financing and the inclusion of a wide range of actions toward participation.
Mobilization for collective market shaping: interplay of innovation and issue networks
Authors: Mehtälä Mari , Lehtimäki Tuula , Komulainen Hanna , Salmi Asta
Published: January 2025

Purpose

The purpose of this paper is to investigate network mobilization for collective market shaping. The authors focus on sustainable innovations that require broad cross-sectoral mobilization to create collective action among network actors. By drawing on insights from mobilization in innovation and issue networks, the authors shed light on the role of these two different networks in mobilizing collective action and triggering collective market shaping for sustainable innovations.

Design/methodology/approach

This paper presents a qualitative case study on the commercialization of a new low-carbon eco-concrete. The eco-concrete faces significant challenges in entering the market, due to the construction industry’s entrenched practices and institutional arrangements. These challenges emphasize the critical need for mobilizing collective action to generate the momentum for market change.

Findings

The findings reveal four types of interplay between mobilization in innovation and issue networks: synergistic and complementary mobilization that can reinforce collective market shaping and conflicting and diluting mobilization that can impede collective action and hinder the market shaping for sustainable innovations.

Originality/value

This paper contributes to a more comprehensive understanding of the role of mobilization in triggering collective market shaping. In particular, this research sheds light on the early stages of market shaping for sustainable innovations where broad mobilization for collective action is critical.
Implementing the Uganda lower secondary competence-based curriculum: the equity question
Authors: Barasa Mercy Chemutai , Ssentamu Proscovia Namubiru , Chang’ach John Koskey , Kurgat Susan Jepkoech
Published: January 2025

Purpose

This paper aims to explore the extent to which the Uganda lower secondary curriculum (LSC) reform, instituted in January 2020, has ensured equitable educational opportunities for secondary school learners considering school and learner socio-economic status.

Design/methodology/approach

A qualitative approach was adopted in which the experiences and perceptions of both facilitators and implementers of the reform were gathered using interviews and lesson observations.

Findings

Data revealed disparities among high and low socio-economic-status schools in their preparedness and capacity to implement the reform, with the consequence of divergent educational opportunities for learners in these contexts.

Research limitations/implications

The sample was limited to government-aided secondary schools and thus excluded private schools; the majority in Uganda. This means that the findings may be limited in generalizability. However, the majority of private schools serve the lower socio-economic demographic, so the study findings and implications may extend to them as well.

Practical implications

The findings suggest that unless the government intervenes with measures to boost the capacity of schools in low socio-economic contexts to implement the reform, the outcome of the curriculum may be a society further stratified along socio-economic lines.

Social implications

The findings indicate that the new LSC may contribute greatly to social stratification through disparate educational opportunities for different sections of the Ugandan populace. This could work against national socio-economic ambitions and also lead to non-achievement of the UN SDG4 of quality, equitable, inclusive education for all.

Originality/value

This paper demonstrates how Uganda, a developing nation, is faring in the achievement of the global educational policy goal of equity in the implementation of its competence-based LSC reform. It highlights key policy and research gaps that should be addressed to promote equitable learning opportunities for all learners.
Parametric simulation of piezoelectric transducer based on finite element method
Authors: Chen Jin , Wang Junwei , Zhu RuiYun , Zhang Wenyue , Teng Duo
Published: January 2025

Purpose

Finite element analysis of underwater transducers typically requires a high level of expertise, and the iterative process of testing various sizes, material parameters and other factors is often inefficient. To address this challenge, this paper aims to introduce underwater transducer parametric simulation (UTPS) software to streamline the design and optimization process.

Design/methodology/approach

The design methodology integrates the strengths of ANSYS Parametric Design Language (APDL) for parametric design with the Qt Creator framework for developing a visual interface. C++ is used to encapsulate complex, hard-to-master APDL macros and interact with ANSYS software to execute the relevant APDL macros, performing finite element analysis on the underwater transducer in the background. The results are then processed and displayed on the visual interface.

Findings

UTPS enables parametric modeling, modal analysis, harmonic response analysis and directivity analysis of underwater transducers. Users only need to input parameters into the software interface to obtain the transducer’s performance, significantly improving work efficiency and lowering the professional threshold. A prototype transducer was fabricated and tested based on UTPS results, which confirmed the accuracy of the software.

Originality/value

This paper presents an innovative parametric simulation tool for underwater transducers, combining finite element analysis and APDL to simplify and expedite the design process. UTPS reduces the need for specialized knowledge, cutting down on training costs, while its parametric design capabilities accelerate the design process, saving resources.
Development of a Recombinant Omicron BA.1 Subunit Vaccine Candidate in Pichia pastoris
Authors: Kalyoncu Sibel , Sayili Dogu , Kuyucu Ayca Zeybek , Soyturk Hakan , Gullu Seyda , Ersayan Busra , Tarman Ibrahim Oguzhan , Avci Mehmet Ender , Mert Olcay , Haskok Umut , Tekin Ege , Akinturk Huseyin , Orkut Ridvan , Demirtas Aysegul , Tilmensagir Idil , Ulker Ceren , Gungor Bilgi , Inan Mehmet
Published: January 2025

Low‐cost and safe vaccines are needed to fill the vaccine inequity gap for future pandemics. Pichia pastoris is an ideal expression system for recombinant protein production due to its cost‐effective and easy‐to‐scale‐up process. Here, we developed a next‐generation SARS‐CoV2 Omicron BA.1‐based recombinant vaccine candidate expressed in P. pastoris. The receptor binding domain of Omicron BA.1 spike protein (RBD‐Omicron) was produced at 0.35 g/L in supernatant. With a 60% recovery after two‐step purification, RBD‐Omicron showed 99% purity. After in vitro characterisation of purified RBD‐Omicron via chromatography, mass spectrometry, calorimetry and surface plasmon resonance‐based methods, it was injected into mice for immunization studies. Three different doses of Alum and CpG adjuvanted RBD‐Omicron were investigated and 10 μg RBD‐Omicron gave the highest antigenicity. After two doses of vaccination, IgG titers in mice serum reached to more than 106. These serum antibodies also recognized earlier (Delta Plus: B.1.617.2) and later (Eris: EG.5, Pirola: BA.2.86) SARS‐CoV2 variants. The long‐term immunological response in mice was measured by analyzing serum antibody titers and T‐cell response of splenocytes after 60 weeks. Interestingly, IgG titers and Th1 response were significantly high even after a year. Omicron subvariants are dominantly circulating in the world, so Omicron sub‐lineage‐based vaccines can be used for future pandemics. The RBD‐Omicron‐based vaccine candidate developed in this study is suitable for technology transfer and transition into the clinic.
Precision Psychobiotics for Gut–Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy
Authors: Slykerman Rebecca F. , Davies Naomi , Vlckova Klara , O'Riordan Kenneth J. , Bassett Shalome A. , Dekker James , Schellekens Harriët , Hyland Niall P. , Clarke Gerard , Patterson Elaine
Published: January 2025

Advancing microbiome–gut–brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo. For the therapeutic application of live microbial psychobiotics, consensus on their application as adjunct treatments to conventional neuromodulators, use in unmedicated populations or in at‐risk cohorts with sub‐clinical symptomatology is warranted. This missing information on both sides of the therapeutic equation when treating central nervous system (CNS) conditions makes psychobiotic research challenging, especially when compared to other pharmaceutical or functional food approaches. Expediting the transition from positive preclinical data to proven benefits in humans includes interpreting the promises and pitfalls of animal behavioural assays, as well as navigating mechanism‐informed decision making to select the right microbe(s) for the job. In this review, we consider how these decisions can be supported in light of information accrued from a range of clinical studies across healthy, at‐risk and pathological study populations, where specific strains have been evaluated in the context of gastrointestinal physiology, brain function and behaviour. Examples of successful, partial and unsuccessful translation from bench to bedside are considered. We also discuss the developments in in silico analyses that have enhanced our understanding of the gut microbiome and that have moved research towards pinpointing the host–microbe interactions most important for optimal gut–brain axis function. Combining this information with knowledge from functional assays across in vitro and ex vivo domains and incorporating model organisms can prime the discovery pipelines with the most promising and rationally selected psychobiotic candidates.