bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does global signal regression alter fMRI connectivity patterns related to EEG activity? An EEG-fMRI study in humans
Authors: Xifra-Porxas Alba , Kassinopoulos Michalis , Prokopiou Prokopis , Boudrias Marie-Hélène , Mitsis Georgios. D. 
Published: April 2024

AbstractFunctional brain connectivity measures extracted from resting-state functional magnetic resonance imaging (fMRI) scans have generated wide interest as potential noninvasive biomarkers. In this context, performing global signal regression (GSR) as a preprocessing step remains controversial. Specifically, while it has been shown that a considerable fraction of global signal variations is associated with physiological and motion sources, GSR may also result in removing neural activity. Here, we address this question by examining the fundamental sources of resting global signal fluctuations using simultaneous electroencephalography (EEG)-fMRI data combined with cardiac and breathing recordings. Our results suggest that systemic physiological fluctuations account for a significantly larger fraction of global signal variability compared to electrophysiological fluctuations. Furthermore, we show that GSR reduces artifactual connectivity due to heart rate and breathing fluctuations, but preserves connectivity patterns associated with electrophysiological activity within the alpha and beta frequency ranges. Overall, these results provide evidence that the neural component of resting-state fMRI-based connectivity is preserved after the global signal is regressed out.
Nanopore sequencing-based episignature detection
Authors: Geysens Mathilde , Huremagic Benjamin , Souche Erika , Breckpot Jeroen , Devriendt Koenraad , Peeters Hilde , Buggenhout Griet Van , Esch Hilde Van , Bogaert Kris Van Den , Vermeesch Joris Robert 
Published: April 2024

ABSTRACTBackgroundA subset of developmental disorders (DD) is characterized by disease-specific genome-wide methylation changes. These episignatures inform about underlying pathogenic mechanisms and can be used to assess the pathogenicity of genomic variants as well as confirm clinical diagnoses. Currently, episignature detection requires the use of indirect methylation profiling microarrays. We hypothesized that long-read whole genome sequencing would not only enable the detection of single nucleotide variants and structural variants but also episignatures.MethodsGenome-wide nanopore sequencing was performed in forty controls and twenty patients with confirmed or suspected episignature-associated DD, representing thirteen distinct diseases. Following variant and methylome calling, hierarchical clustering and dimensional reduction were used to determine the compatibility with microarray-based episignatures. Subsequently, we developed a support vector machine for each DD.ResultsNanopore sequencing based methylome patterns were concordant with microarray-based episignatures. Our classifier identified episignatures in 17/20 disease samples and none of the controls. The remaining three patient samples were classified as controls by both our classifier and a commercial microarray assay. In addition, we identified all underlying pathogenic single nucleotide and structural variants and showed haplotype-aware skewed X-inactivation evaluation directs clinical interpretation.ConclusionThis proof-of-concept study demonstrates nanopore sequencing enables concurrent haplotyped genomic and epigenomic analyses.
The Genomic Architecture of Circulating Cytokine Levels Points to Drug Targets for Immune-Related Diseases
Authors: Konieczny Marek J. , Omarov Murad , Malik Rainer , Richardson Tom G. , Baumeister Sebastian-Edgar , Bernhagen Jürgen , Dichgans Martin , Georgakis Marios K. 
Published: April 2024

AbstractCirculating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals. We detected 359 significant associations between cytokine levels and variants in 169 independent loci, including 150trans- and 19cis-acting loci. Integration with transcriptomic data point to key regulatory mechanisms, such as the buffering function of ACKR1 acting as scavenger for multiple chemokines and the role of TRAFD1 in modulating the cytokine storm triggered by TNF signaling. Applying Mendelian randomization (MR), we detected a network of complex cytokine interconnections with TNF-b, VEGF, and IL-1ra exhibiting pleiotropic downstream effects on multiple cytokines. Drug targetcis-MR paired with colocalization revealed G-CSF/CSF-3 and CXCL9/MIG as potential causal mediators of asthma and Crohn’s disease, respectively, but also a potentially protective role of TNF-b in multiple sclerosis. Our results provide an overview of the genetic architecture of circulating cytokines and could guide the development of targeted immunotherapies.
Combiningin vivoandin vitroapproaches to better understand host-pathogen interactions
Authors: Holdbrook Robert , Reavey Catherine E. , Randall Joanna L. , Andongma Awawing A. , Tummala Yamini , Simpson Stephen J. , Smith Judith A. , Cotter Sheena C. , Wilson Kenneth 
Published: April 2024

ABSTRACTNutrition often shapes the outcome of host-parasite interactions, however understanding the mechanisms by which this occurs is confounded by the intimate nature of the association and by the fact that the host and parasite may compete for the same limiting nutrients. One way of disentangling this interaction is to combinein vivoandin vitroapproaches. Here, we explore the role of host nutrition in determining the outcome of infections using a model insect-bacterium system: the cotton leafwormSpodoptera littoralisand the blood-borne bacteriumXenorhabdus nematophila.Spodoptera littoralislarvae were reared on one of a series of 20 chemically-defined diets ranging in their protein: carbohydrate (P:C) ratio and caloric density. They were then challenged with either a fixed dose ofX. nematophilacells (live or dead) or were sham-injected. Survivorship of larvae challenged with live bacterial cells was strongly dependent on the protein levels of the diet, with mortality being highest on low-protein diets. This trend was reflected in the bacterial growth ratein vivo, which peaked in larvae fed low-protein diets.To determine whetherin vivobacterial growth rates were driven by blood nutrients, rather than an enhanced host immune response, we generated 20 synthetic haemolymphs (‘nutribloods’) that mimicked the nutritional content of host blood. Bacterial growth rate in the nutribloods was also negatively impacted by their protein content suggesting that nutrient availability and not host immunity was driving the interaction. By comparing standardized bacterial growth ratesin vivoandin vitro, we conclude that the outcome of this host-parasite interaction is largely driven by ‘bottom-up’ effects of nutrients on bacterial growth, rather than by ‘top-down’ effects of nutrients on host-mediated immune responses. The outcome of host-parasite interactions is typically assumed to be strongly determined by the host immune response. The direct effects of nutrition have been underexplored and may have broad consequences for host-parasite interactions across taxa.
Site-Specific Investigation of DNA Holliday Junction Dynamics and Structure with 6-Methylisoxanthopterin, a Fluorescent Guanine Analog
Authors: Lombardo Zane , Mukerji Ishita 
Published: April 2024

AbstractDNA Holliday Junction (HJ) formation and resolution is requisite for maintaining genomic stability in processes such as replication fork reversal and double-strand break repair. If HJs are not resolved, chromosome disjunction and aneuploidy result, hallmarks of tumor cells. To understand the structural features that lead to processing of these four-stranded joint molecule structures, we seek to identify structural and dynamic features unique to the central junction core. We incorporate the fluorescent guanine analog 6-methylisoxanthopterin (6-MI) at ten different locations throughout a model HJ structure to obtain site-specific information regarding the structure and dynamics of bases relative to those in a comparable sequence context in duplex DNA. These comparisons were accomplished through measuring fluorescence lifetime, relative brightness, fluorescence anisotropy, and thermodynamic stability, along with fluorescence quenching assays. These time-resolved and steady-state fluorescence measurements demonstrate that the structural distortions imposed by strand crossing result in increased solvent exposure, less stacking of bases and greater extrahelical nature of bases within the junction core. The 6-MI base analogs in the junction reflect these structural changes through an increase in intensity relative to those in the duplex. Molecular dynamics simulations performed using a model HJ indicate the primary sources of deformation are in the shift and twist parameters of the bases at the central junction step. These results suggest that junction-binding proteins may use the unique structure and dynamics of the bases at the core for recognition.
Enhancing Agrobacterium-Mediated Soybean Transformation Efficiency with an Auxiliary Solution
Authors: Chen Luying , Wang Liang , Li Yongguang , Han Shaojie 
Published: April 2024

AbstractSoybean provides oil, protein, and biofuel. Efficient transformation systems are vital for advancing soybean research. Currently,Agrobacterium rhizogenes-mediated transformation is the predominant method for facilitating rapid transformation, producing transgenic hairy roots. However, the limitations of soybean transformation technology primarily originate from its low efficiency and genotype dependency, leaving significant room for improvement in the development more universally applicable and efficient methods. In this study, we explored the enhancement of soybean transformation efficiency through the generation and validation of three reporter vectors (ZsGreen, TdTomato, and Ruby) and the strategic use ofAgrobacteriumAuxiliary Solution (AAS) containing Silwet L-77 and hormone mixtures. Our findings demonstate that the incorporation of hormone mixtures and Silwet L-77 into AAS significantly improves hairy root transformation rates. Specifically, the combination of hormone mixtures with Silwet L-77 substantially increased both total root and cotyledon transformation efficiencies compared to the control. We also assessed the impact of vector size on transformation efficiency, observing a notable decrease in efficiency with larger vectors such as the Ruby cassette compared to smaller markers like GFP and RFP. Furthermore, our study examined the effects of AAS on the co-transformation rate of two separate vectors, revealing a slight but significant reduction in efficiency compared to single vector transformations. Additionally, we evaluated the role of AAS in enhancing soybean hypocotyl transformation rates in composite soybean plants across various varieties. The results consistently showed an increase in both positive roots and explant efficiencies with the addition of AAS, indicating its broad applicability and effectiveness in soybean transformation. However, significant varietal differences in transformation rates were observed, particularly between “Forrest” and other varieties such as “Williams 82” and “Dongnong 50”. In summary, our research emphasizes the significant role of auxiliary agents and vector size in optimizing soybean transformation techniques, providing valuable insights for future advancements in soybean genetic modification and biotechnological research.
Single Channel Electrocardiography Optimizes the Diagnostic Accuracy of Bicycle Ergometry
Authors: Marzoog Basheer Abdullah , Abdullaev Magomed , Suvorov Alexander , Chomakhidze Peter , Gognieva Daria , Gagarina Nina Vladimirovna , Mozzhukhina Natalia , Kostin Sergey Vladimirovich , Bestavashvili Afina Aftandilovna , Fominykha Ekaterina , Kopylov Philipp 
Published: April 2024

AbstractBackgroundIschemic heart disease (IHD) has the highest mortality rate in the globe. This returns to the poor diagnostic and therapeutic strategies including the early prevention methods.AimsTo assess the changes in the single channel electrocardiography (SCECG) at rest and on exercise test in patients with vs without IHD confirmed by stress computed tomography myocardial perfusion (CTP) imaging with vasodilatation stress-test.ObjectivesIHD frequently have preventable risk factors and causes that lead to the disease appearance. However, the lack of the proper diagnostic and prevention tools remains a global challenge in or era despite the current scientific advances.Material and methodsA single center observational study included 38 participants from Moscow. The participants aged ≥ 40 years and given a written consent to participate in the study. Both groups, G1=19 with vs G2=19 without post stress induced myocardial perfusion defect, passed consultation by cardiologist, anthropometric measurements, blood pressure and pulse rate, echocardiography, cardio-ankle vascular index, performing bicycle ergometry, recording 3-minutes SCECG (using CARDO-QVARK ) before and just after bicycle ergometry, and then performing CTP. The LASSO regression with nested cross-validation was used to find association between CARDO-QVARK parameters and the existence of the perfusion defect. Statistical processing carried out using the R programming language v4.2 and Python v.3.10 [^R].ResultsThe CARDO-QVARK parameters analysis have a specificity 63.2 % [95 % confidence interval (CI); 0.391 ; 0.833], sensitivity 73.7 % [95 % CI ; 0.533 ; 0.929], area under the curve (AUC) 68.4 % [95 % CI ; 0.527 ; 0.817] in compare to bicycle ergometry (AUC; 55.3 %), based on our study results.ConclusionThe SCECG have significantly higher diagnostic accuracy in compare to bicycle ergometry. CARDO-QVARK has the potential to improve the diagnostic accuracy of the bicycle ergometry.OtherFurther investigations required to uncover the hidden capabilities of CARDO-QVARK in the diagnosis of ischemic heart disease.
The potential impact of the spreading of highly transmissible Omicron variant XBB.1.5 and JN.1 on the evolution of SARS-CoV-2
Authors: Yi Buqing 
Published: April 2024

AbstractIn spite of three-year pandemic time caused by Covid-19, the trend and impact of the evolution of SARS-CoV-2 remain unclear. For newly emerging variants, it is still hard to predict how possibly they could impact the pandemic/endemic course. The spreading of the highly transmissible variant XBB.1.5 and JN.1 has brought many questions. Could the high transmission ability of such variant lead to a different global spreading pattern compared to other previously existing variants of concern (VOCs)? How that may possibly affect the further evolution of SARS-CoV-2? This study aimed to explore the evolution course of SARS-CoV-2 variants, with focus on VOCs. The investigation was carried out through integration of multiple virus genomic epidemiology approaches. Phylogeny and phylodynamic analyses were used to investigate dynamic changes of virus evolution course. Through this study, an overview check of the evolution events of SARS-CoV-2 VOCs, including the alpha variant, delta variant and omicron variant, has been performed, and the further course of evolution has been predicted, especially taking the potential impact of the spreading of XBB.1.5 and JN.1 into consideration. Furthermore, the early spreading pattern of XBB.1.5 was compared with the early spreading patterns of BQ.1.1 to investigate the impact of evolution on virus spreading pattern. The information acquired through this study provided insights into the effect of SARS-CoV-2 evolution on spreading pattern and the potential impact of the spreading of XBB.1.5 and JN.1 on the further evolution of SARS-CoV-2.
Binette: a fast and accurate bin refinement tool to construct high quality Metagenome Assembled Genomes
Authors: Mainguy Jean , Hoede Claire 
Published: April 2024

AbstractMetagenomics enables the study of microbial communities and their individual members through shotgun sequencing. An essential phase of metagenomic analysis is the recovery of metagenome-assembled genomes (MAGs). In a metagenomic analysis, sequence reads are assembled into contigs, which are then grouped into bins based on common characteristics - a process known as binning - to generate MAGs. The approach of applying multiple binning methods and combining them in a process called bin refinement allows us to obtain more and higher quality MAGs from metagenomic datasets. We present Binette, a bin refinement tool inspired by metaWRAP’s bin refinement module, which addresses the limitations of the latter and ensures better results. Binette achieves this by creating new hybrid bins using basic set operations from the input bin sets. CheckM2 is then used to assess bin quality and select the best possible bins.
Characterization of the novelSmsHSP24.1Promoter: Unveiling its abiotic stress-inducible expression in transgenic Eggplant (Solanum melongenaL.)
Authors: Khatun Mst. Muslima , Khan Imran , Borphukan Bhabesh , Das Keshob Chandra , Khan Haseena , Islam Mohammad Riazul , Reddy Malireddy K , Salimullah Md 
Published: April 2024

AbstractPromoters play a pivotal role in regulating gene expression, orchestrating vital processes in plants, including their responses to various environmental stresses. In this study, we focus on the comprehensive characterization of theSmsHSP24.1promoter, a novelcis-acting element, within the context of transgenic Eggplant (Solanum melongenaL.). This detailed analysis shed light on the intricate mechanisms governingSmsHSP24.1promoter-driven gene regulation, particularly in response to adverse environmental challenges such as heat, salt and drought stressors offering valuable insights into its role in plant stress adaptation. The advances in our understanding of promoter-driven gene regulation also contribute to the broader goal of enhancing crop resilience to abiotic stresses, positioning theSmsHSP24.1promoter as a promising tool in agricultural biotechnology applications.Highlights:Demonstrated that the full-length 2.0 kb SmsHSP24.1 promoter significantly enhances gene expression under heat stress, with an observable decline in expression with promoter truncation.Identified specific regulatory elements within the SmsHSP24.1 promoter that are decisive for inducible expression in response to abiotic stresses such as heat, salt, and drought.Highlighted the utility of the SmsHSP24.1 promoter in crop improvement programs, offering a tool for developing transgenic plant tolerance to combined stresses.
Component specific responses of the microbiomes to common chemical stressors in the human food chain
Authors: Wasimuddin  , Chiaia-Hernandez Aurea , Terrettaz Céline , Thoenen Lisa , Caggìa Veronica , Matteo Pierre , Coll-Crespi Miquel , Notter Matheus , Mukherjee Mohana , Chavez-Capilla Teresa , Ronchi Francesca , Ganal-Vonarburg Stephanie C. , Grosjean Martin , Bigalke Moritz , Spielvogel Sandra , Macpherson Andrew , Mestrot Adrien , Hapfelmeier Siegfried , Erb Matthias , Schlaeppi Klaus , Ramette Alban 
Published: April 2024

AbstractAlong a food chain, microbiomes occur in each component and often contribute to the functioning or the health of their host or environment. ‘One Health’ emphasizes the connectivity of each component’s health. Chemical stress typically causes dysbiotic microbiomes, but it remains unclear whether chemical stressors consistently affect the microbiomes along food chain components. Here, we systematically challenged a model food chain, including water, sediments, soil, plants, and animals, with three chemical stresses consisting of arsenic (a toxic trace element), benzoxazinoids (an abundant bioactive plant metabolites), and terbuthylazine (an herbicide typically found along a human food chain). The analysis of 1,064 microbiome profiles for commonalities and differences in their stress responses indicated that chemical stressors decreased microbiome diversity in soil and animal, but not in the other microbiomes. In response to stress, all food chain communities strongly shifted in their composition, generally becoming compositionally more similar to each other. In addition, we observed stochastic effects in host-associated communities (plant, animal). Dysbiotic microbiomes were characterized by different sets of bacteria, which responded specifically to the three chemical stressors. Microbial co-occurrence patterns significantly shifted with either decreased (water, sediment, plant, animal) or increased (soil) network sparsity and numbers of keystone taxa following stress treatments. This suggested major re-distribution of the roles that specific taxa may have, with the community stability of plant and animal microbiomes being the most affected by chemical stresses. Overall, we observed stress- and component-specific responses to chemical stressors in microbiomes along the model food chain, which could have implications on food chain health.
A Blueprint for Broadly Effective Bacteriophage Therapy Against Bacterial Infections
Authors: Kim Minyoung Kevin , Chen Qingquan , Echterhof Arne , McBride Robert C. , Pennetzdorfer Nina , Banaei Niaz , Burgener Elizabeth B. , Milla Carlos E. , Bollyky Paul L. 
Published: April 2024

SummaryBacteriophage therapy is a tantalizing therapeutic option for anti-microbial resistant bacterial infections but is currently limited to personalized therapy due to the narrow host range of individual phages. Theoretically, cocktails incorporating numerous phages targeting all possible bacterial receptor specificities could confer broad host range. Practically, however, extensive bacterial diversity and the complexity of phage-phage interactions precludes this approach. Here, using screening protocols for identifying “complementarity groups” of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent emergence of bacterial resistance. Further, phage complementarity groups have characteristic interactions with particular antibiotic classes, making it possible to predict phage-antibiotic as well as phage-phage interactions. Using this strategy, we generate three phage-antibiotic cocktails, each effective against >96% of 153Pseudomonas aeruginosaclinical isolates, including when used in biofilm cultures and wound infectionsin vivo. We similarly develop effectiveStaphylococcus aureusphage-antibiotic cocktails and demonstrate the utility of combined cocktails against polymicrobial (mixedP. aeruginosa/S. aureus) cultures, highlighting the broad applicability of this approach. These studies establish a blueprint for effective, broad-spectrum phage therapy cocktails and enable off-the-shelf phage-based therapeutics for antimicrobial-resistant bacterial infections.