bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of Nomograms for predicting Coronary Artery Calcification and Severe Coronary Artery Calcification: a retrospective cross-sectional study
Authors: Xue Peng , Lin Ling , Li Peishan , Deng Zhengting , Chen Xiaohu , Zhuang Yanshuang 
Published: September 2024

AbstractIntroductionThere is a significant lack of effective pharmaceutical interventions for treating coronary artery calcification (CAC). Severe CAC (sCAC) poses a formidable challenge to interventional surgery and exhibits robust associations with adverse cardiovascular outcomes. Therefore, it is imperative to develop tools capable of early-stage detection and risk assessment for both CAC and sCAC. This study aims to develop and validate nomograms for the accurate prediction of CAC and sCAC.MethodsThis retrospective cross-sectional study was conducted in Taizhou, Jiangsu Province, China. CAC assessment was performed using non-gated thoracic CT scans. Demographic data and clinical information were collected from patients who were then randomly divided into a training set (70%) or a validation set (30%). Least absolute shrinkage and selection operator (LASSO) regression as well as multiple logistic regression analyses were utilized to identify predictive factors for both CAC and sCAC development. Nomograms were developed to predict the occurrence of CAC or sCAC events. The models’ performance was evaluated through discrimination analysis, calibration analysis, as well as assessment of their clinical utility.ResultsThis study included 666 patients with an average age of 75 years, of whom 56% were male. 391 patients had CAC, with sCAC in 134 cases. Through LASSO and multiple logistic regression analysis, age increase, hypertension, carotid artery calcification, CHD, and CHADS2score were identified for the CAC risk predictive nomogram with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.845(95%CI 0.809-0.881) in the training set and 0.810(95%CI 0.751-0.870) in the validation set. Serum calcium level, carotid artery calcification, and CHD were identified for the sCAC risk predictive nomogram with an AUC of 0.863(95%CI 0.825-0.901) in the training set and 0.817(95%CI 0.744-0.890) in the validation set. Calibration plots indicated that two models exhibited good calibration ability. According to the decision curve analysis (DCA) results, both models have demonstrated a positive net benefit within a wide range of risks.ConclusionsThe present study has successfully developed and validated two nomograms to accurately predict CAC and sCAC, both of which have demonstrated robust predictive capabilities.
Neutrophil NADPH oxidase breaks the inflammatory IL-1β/IL-17A circuit to enhance pathogen clearance during respiratory virus infections
Authors: Sofoluwe Aderonke , Petropoulos Angelos , Goomanee Abhilesh Salil , Ali-Khan Zehra Fatima , Warnatsch Annika 
Published: September 2024

SummaryRespiratory virus infections are invariably accompanied by an increase in oxidative stress, characterised by elevated production of Reactive Oxygen Species (ROS) in the lung, which plays a pivotal role in both pathogenesis and host defence. Using a mouse model, neutrophil NADPH Oxidase 2 (Nox2) emerges as a key player, primarily responsible for generation of ROS during the early phases of Influenza A Virus (IAV) infection. Neutrophil Nox2-derived ROS display a multifaceted role, not only unleashing oxidative stress but in turn curbing neutrophil-derived IL-1β signalling. Absence of neutrophil Nox2 triggered heightened production of IL-1β, promoting the proliferation of IL-17-producing gamma delta (γδ) T cells. This early self-amplified augmentation of the IL-β/IL-17 axis counteracted the antiviral interferon response against IAV infection in mice. We extended our findings to humans. Similar patterns of ROS production and cytokine regulation were observed in human neutrophils when exposed to virus analogue poly(I:C) and SARS-CoV-2. Our discovery highlights that ROS, often associated with harm, play a dual role by regulating cytokine signalling and thus influencing the immune response against respiratory viruses.HighlightsNeutrophil NADPH oxidase 2 is the predominant source of ROS production early after influenza A virus infection.Neutrophil Nox2-derived ROS uniquely suppress IL-1β, influencing γδ17T cell proliferation.In absence of neutrophil Nox2, increased neutrophil-derived IL-1β drives proliferation of γδ17T cells.Early amplification of the IL-β/IL-17 axis counteracts the antiviral interferon response in IAV-infected mice.Virus infection induces a self-perpetuating loop between human blood-derived IL-1β-producing neutrophils and IL-17-secreting γδ T cells.
CLIMATE BRAIN - Questionnaires, Tasks and the Neuroimaging Dataset
Authors: Zaremba Dominika , Kossowski Bartosz , Wypych Marek , Jednoróg Katarzyna , Michałowski Jarosław M. , Klöckner Christian A. , Wierzba Małgorzata , Marchewka Artur 
Published: September 2024

AbstractClimate change presents a fundamental threat to human populations and ecosystems across the globe. Neuroscience researchers have recently started developing ways to advance research on this topic. However, validated questionnaires, experimental stimuli, and fMRI tasks are still needed. Here we describe the CLIMATE BRAIN dataset, a multimodal collection of questionnaire, behavioural, and neuroimaging data related to climate change, acquired from 160 healthy individuals. In particular, it includes data from (1) various questionnaire measures, including the Inventory of Climate Emotions (ICE); (2) a neuroimaging task for measuring emotional reactions to standardized Emotional Climate Change Stories (ECCS); and (3) a neuroimaging task based on Carbon Emission Task (CET) to measure climate action-taking. For technical validation, we provide image quality metrics and show the evidence for the effectiveness of tasks consistent with prior studies. To our knowledge, the proposed dataset is currently the only publicly available resource specifically designed to investigate human brain responses to climate change.
Comprehensive intra-host infection kinetics reveals high arbo-flavivirus transmission potential by neglected vector species,Aedes scutellaris
Authors: Samung Yudthana , Pengon Jutharat , Pethrak Chatpong , Pakparnich Phonchanan , Thaiudomsup Saranya , Suksirisawat Kittitat , Phayakkaphol Anon , Eiamsam-ang Songpol , Phanitchat Thipruethai , Sartsanga Channarong , Jantra Tararat , Sriwichai Patchara , Jupatanakul Natapong 
Published: September 2024

AbstractBackgroundDengue virus (DENV) and Zika virus (ZIKV) are primarily transmitted byAedesmosquitoes. As most studies on vector competence have focused onAedes aegyptiandAedes albopictuswhile neglecting otherAedesspecies, it is possible that the transmission risks might be underestimated. it is necessary to examine additional species that could potentially serve as competent vectors. This is particularly important considering the potential expansion of their geographical range due to climate change or species-specific vector reduction interventions.Methodology/Principal FindingsIn this study, we examined the infection kinetics and transmission potential ofAedes scutellarisfrom Thailand, comparing toAe. aegyptiandAe. albopictus. Our findings demonstrated thatAe. scutellarisandAe. albopictushad lower rates of midgut infection compared toAe. aegyptidue to smaller blood meal sizes during feeding. However, once the infection has establishedAe. scutellarisexhibited efficient replication of ZIKV and DENV1-4 in the midguts, secondary organs, and salivary glands. Notably,Ae. scutellarishad a low salivary gland escape barrier, with comparable transmissibility asAe. aegyptiwhen inoculated with the same viral load.ConclusionThis study highlights the potential ofAe. scutellarisas a vector for DENV and ZIKV and emphasizes the importance of considering neglected mosquito species in arbovirus transmission and surveillance efforts.Author SummaryDengue and Zika are viral infections caused by arthropod-borne flaviviruses, and spread primarily through the bite of infectedAedesmosquitoes. Most research on DENV and ZIKV transmission has primarily focused onAedes aegyptiandAedes albopictuswhile otherAedesspecies are overlooked, thus the epidemiology of the transmission might be underestimated. With climate change together with species-specific mosquito population reduction interventions these neglectedAedesspecies could become increasingly important in sustaining virus transmission. In this study, we examinedAedes scutellaris, a mosquito species that co-habitats withAe. aegyptiandAe. albopictus, to assess its ability to transmit DENV and ZIKV using a combination of blood feeding and intrathoracic injection methods. Our findings show that althoughAe. scutellarishad lower initial infection rates due to smaller blood meals, DENV and ZIKV were able to replicate and transmit at levels comparable toAe. aegyptiwhen exposed to similar virus loads. This highlights the need to study a broader range of species to improve virus control and outbreak prevention strategies.
Both competition and frequency-dependence determine community dynamics in a dune heath ecosystem
Authors: Damgaard Christian , Kaae Mathias Emil , Bak Jesper Leth 
Published: September 2024

AbstractTo investigate community dynamics in a dune heath ecosystem, plant growth was measured in a five-block manipulated experiment with four nitrogen levels using the pin-point method. It was demonstrated that both Lotka-Volterra type interspecific competition and frequency-dependency play significant roles in determining plant growth. For modelling simplicity, plant taxa were divided into heather, wavy hair-grass, and all other vascular species. Significant interspecific competition was observed among all species, except wavy hair-grass on the growth of all other vascular species, and nitrogen addition was found to increase the competitive effect of heather on the growth of all other vascular species. Both heather and wavy hair-grass showed positive feedback dynamics on growth when they were relatively dominant at the plot scale and the effect increased with added nitrogen. Such positive feedback dynamics may lead to the formation of patches, which are a characteristic feature of heath ecosystems. Oppositely, there was a beneficial effect of being relatively rare on the growth of all other vascular species in plots with added nitrogen. The study highlights the importance of the combined effects of interspecific competition and frequency-dependency in regulating plant communities and, consequently, undermines both theoretical and empirical conclusions of modern coexistence theory.
The epitranscriptomic m6A RNA modification modulates synaptic function in ageing and in a mouse model of synucleinopathy
Authors: Chopra Avika , Xylaki Mary , Yin Fanzheng , Castro-Hernández Ricardo , Merghani Madiha , Grande Valentina , Mollenhauer Brit , Fischer André , Outeiro Tgiago F. 
Published: September 2024

AbstractN6-methyladenosine (m6A) is the most abundant and conserved transcriptional modification in eukaryotic RNA, regulating RNA fate. While the functions of m6A in the development of the mammalian brain have been extensively studied, its roles in synaptic plasticity, cognitive decline, motor function, or other brain circuits remain underexplored. To date, the role of this modification in Parkinson’s disease (PD) and other synucleinopathies has been largely unknown. Here, we investigated the m6A epitranscriptome in a mouse model of synucleinopathy. We performed m6A RNA immunoprecipitation sequencing (meRIP-seq) to obtain the m6A epitranscriptome of the midbrain in young (3 mo) and aged (15 mo) A30P-aSyn transgenic mice (aSyn Tg) and C57BL6 control wild type (Wt) mice. We observed hypermethylation of synaptic genes in 3 mo aSyn Tg mice compared to age-matched Wt mice. This methylation was reduced during ageing, with synaptic genes becoming increasingly hypomethylated. Using immunofluorescence imaging alongside biochemical analysis, we further investigated the expression of m6A regulatory enzymes — writer, N6-Adenosine-Methyltransferase Complex Catalytic Subunit (METTL3); reader, YTH N6-methyladenosine RNA-binding protein (YTHDF1); and eraser, fat mass and obesity-associated protein (FTO) — in the cortex, striatum, hippocampus, and cerebellum of Wt and aSyn Tg mice, as well as in primary cortical neuronal cultures. We observed that the levels of METTL3, YTHDF1 and FTO were similar between Wt and aSyn Tg mice. Interestingly, the writer protein METTL3 was found in both the nucleus and in the post-synaptic compartment in neuronal cultures. Our findings suggest that alterations in the regulation of m6A RNA methylation may be associated with neurodegeneration and ageing and that this level of epitranscriptomic regulation plays a significant role at the synapse.
“Mitotic” kinesin-5 is a dynamic brake for axonal growth
Authors: Lu Wen , Lee Brad S. , Ying Deng Helen Xue , Lakonishok Margot , Martin-Blanco Enrique , Gelfand Vladimir I. 
Published: September 2024

During neuronal development, neurons undergo significant microtubule reorganization to shape axons and dendrites, establishing the framework for efficient wiring of the nervous system. Previous studies from our laboratory demonstrated the key role of kinesin-1 in driving microtubule-microtubule sliding, which provides the mechanical forces necessary for early axon outgrowth and regeneration inDrosophila melanogaster. In this study, we reveal the critical role of kinesin-5, a mitotic motor, in modulating the development of postmitotic neurons.Kinesin-5, a conserved homotetrameric motor, typically functions in mitosis by sliding antiparallel microtubules apart in the spindle. Here, we demonstrate that theDrosophilakinesin-5 homolog, Klp61F, is expressed in larval brain neurons, with high levels in ventral nerve cord (VNC) neurons. Knockdown ofKlp61Fusing a pan-neuronal driver leads to severe locomotion defects and complete lethality in adult flies, mainly due to the absence of kinesin-5 in VNC motor neurons during early larval development.Klp61Fdepletion results in significant axon growth defects, both in cultured andin vivoneurons. By imaging individual microtubules, we observe a significant increase in microtubule motility, and excessive penetration of microtubules into the axon growth cone inKlp61F-depleted neurons. Adult lethality and axon growth defects are fully rescued by a chimeric human-Drosophilakinesin-5 motor, which accumulates at the axon tips, suggesting a conserved role of kinesin-5 in neuronal development.Altogether, our findings show that at the growth cone, kinesin-5 acts as a brake on kinesin-1-driven microtubule sliding, preventing premature microtubule entry into the growth cone. This regulatory role of kinesin-5 is essential for precise axon pathfinding during nervous system development.
ADPKD variants in the PKD2 pore helix cause structural collapse of the gate and distinct forms of channel dysfunction
Authors: Palomero Orhi Estarte , DeCaen Paul G. 
Published: September 2024

ABSTRACTPKD2 is a member of the polycystin subfamily of transient receptor potential (TRP) ion channel subunits which traffic and function in primary cilia organelle membranes. Millions of individuals carry pathogenic genetic variants in PKD2 that cause a life-threatening condition called autosomal dominant polycystic kidney disease (ADPKD). Although ADPKD is a common monogenetic disorder, there is no drug cure or available therapeutics which address the underlying channel dysregulation. Furthermore, the structural and mechanistic impact of most disease-causing variants are uncharacterized. Using direct cilia electrophysiology, cryogenic electron microscopy (cryo-EM), and super resolution imaging, we have discovered mechanistic differences in channel dysregulation caused by three germline missense variants located in PKD2’s pore helix 1. Variant C632R reduces protein thermal stability, resulting in impaired channel assembly and abolishes primary cilia trafficking. In contrast, variants F629S and R638C retain native cilia trafficking, but exhibit gating defects. Resolved cryo-EM structures (2.7-3.2Å) of the variants indicate loss of critical pore helix interactions and precipitate allosteric collapse of the channels inner gate. Results demonstrate how ADPKD-causing these mutations have divergent and ranging impacts on PKD2 function, despite their shared structural proximity. These unexpected findings underscore the need for mechanistic characterization of polycystin variants, which may guide rational drug development of ADPKD therapeutics.Regarding polycystin nomenclatureThe revised and current IUPHAR/BPS nomenclature creates ambiguity regarding the genetic identity of the polycystin family members of transient receptor potential ion channels (TRPP), especially when cross-referencing manuscripts that describe subunits using the former system1. Traditionally, the products of polycystin genes (e.g., PKD2) are referred to as polycystin proteins (e.g., polycystin-2). For simplicity and to prevent confusion, we will refer to the polycystin gene name rather than differentiating gene and protein with separate names— a nomenclature we have recently outlined (Annual Reviews in Physiology, Esarte Palomero et al. 2023)2
Context-Seq: CRISPR-Cas9 Targeted Nanopore Sequencing for Transmission Dynamics of Antimicrobial Resistance
Authors: Fuhrmeister Erica R. , Kim Sooyeol , Mairal Shruteek A. , McCormack Caroline , Chieng Benard , Swarthout Jenna M. , Paulos Abigail Harvey , Njenga Sammy M. , Pickering Amy J. 
Published: September 2024

AbstractAntimicrobial resistance (AMR) aligns with a One Health framework in that resistant bacteria and antibiotic resistance genes (ARGs) can be transmitted between humans, animals, and the environment. However, there is a critical need to more precisely understand how and to what extent AMR is exchanged between animals and humans. Metagenomic sequencing has low detection for rare targets such as ARGs, while whole genome sequencing of isolates is burdensome and misses exchange between uncultured bacterial species. We developed a novel, targeted sequencing assay using CRISPR-Cas9 to selectively sequence ARGs and their genomic context with long-read sequencing. Using this method, termed Context-Seq, we investigated overlapping AMR elements containing the ARGsblaCTX-MandblaTEMbetween adults, children, poultry, and dogs in animal-owning households in Nairobi, Kenya. We identified 22 genetically distinct clusters (> 80%ID over ≥ 3000 bp) containingblaTEMand one cluster containingblaCTX-Mthat were shared within and between households. Half of the clusters were shared between humans and animals, while the other half were shared only between animals (poultry-poultry, dog-dog, and dog-poultry). We identified potentially pathogenic hosts of ARGs includingEscherichia coli, Klebsiella pneumonia, andHaemophilus influenzaeacross sample types. Context-Seq complements conventional methods to obtain an additional view of bacterial and mammalian hosts in the proliferation of AMR.
Analysis of polyclonal and monoclonal antibody to the influenza virus nucleoprotein in different oligomeric states
Authors: Myers Mallory L. , Conlon Michael T. , Gallagher John R. , Woolfork De’Marcus D. , Khorrami Noah D. , Park William B. , Stradtman-Carvalho Regan K. , Harris Audray K. 
Published: September 2024

AbstractInfluenza virus nucleoprotein (NP) is one of the most conserved influenza proteins. Both NP antigen and anti-NP antibodies are used as reagents in influenza diagnostic kits, with applications in both clinical practice, and influenza zoonotic surveillance programs. Despite this, studies on the biochemical basis of NP diagnostic serology and NP epitopes are not as developed as for hemagglutinin (HA), the fast-evolving antigen which has been the critical component of current influenza vaccines. Here, we characterized the NP serology of mice, ferret, and human sera and the immunogenic effects of NP antigen presented as different structural complexes. Furthermore, we show that a classical anti-NP mouse mAb HB65 could detect NP in some commercial influenza vaccines. MAb HB65 bound a linear epitope with nanomolar affinity. Our analysis suggests that linear NP epitopes paired with their corresponding characterized detection antibodies could aid in designing and improving diagnostic technologies for influenza virus.
Completing the BASEL phage collection to unlock hidden diversity for systematic exploration of phage-host interactions
Authors: Humolli Dorentina , Piel Damien , Maffei Enea , Heyer Yannik , Agustoni Elia , Shaidullina Aisylu , Willi Luc , Imwinkelried Patrick , Estermann Fabienne , Cuénod Aline , Buser Dominik P. , Alampi Carola , Chami Mohamed , Egli Adrian , Hiller Sebastian , Dunne Matthew , Harms Alexander 
Published: September 2024

AbstractResearch on bacteriophages, the viruses infecting bacteria, has fueled the development of modern molecular biology and inspired their therapeutic application to combat bacterial multidrug resistance. However, most work has so far focused on a few model phages which impedes direct applications of these findings in clinics and suggests that a vast potential of powerful molecular biology has remained untapped. We have therefore recently composed the BASEL collection of Escherichia coli phages (BActeriophage SElection for your Laboratory) which made a relevant diversity of phages infecting the E. coli K-12 laboratory strain accessible to the community. These phages are widely used, but their assorted diversity had remained limited by the E. coli K-12 host. We have therefore now genetically overcome the two major limitations of E. coli K-12, its lack of O-antigen glycans and the presence of resident bacterial immunity. Restoring O-antigen expression resulted in the isolation of diverse additional viral groups like Kagunavirus, Nonanavirus, Gordonclarkvirinae, and Gamaleyavirus, while eliminating all known antiviral defenses of E. coli K-12 additionally enabled us to isolate phages of Wifcevirus genus. Even though some of these viral groups appear to be common in nature, no phages from any of them had previously been isolated using E. coli laboratory strains and they had thus remained largely understudied. Overall, 37 new phage isolates have been added to complete the BASEL collection. These phages were deeply characterized genomically and phenotypically with regard to host receptors, sensitivity to antiviral defense systems, and host range. These results highlighted dominant roles of the O-antigen barrier for viral host recognition and of restriction-modification systems in bacterial immunity. We anticipate that the completed BASEL collection will propel research on phage-host interactions and their molecular mechanisms, deepening our understanding of viral ecology and fostering innovations in biotechnology and antimicrobial therapy.