bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating plant growth-defence trade-offs by modelling the interaction between primary and secondary metabolism
Authors: Zrimec Jan , Correa Sandra , Zagorščak Maja , Petek Marko , Bleker Carissa , Stare Katja , Schuy Christian , Sonnewald Sophia , Gruden Kristina , Nikoloski Zoran 
Published: September 2024

AbstractUnderstanding the molecular mechanisms behind plant response to stress can enhance breeding strategies and help us design crop varieties with improved stress tolerance, yield and quality. To investigate resource redistribution from growth-to defence-related processes in an essential tuber crop, potato, here we generate a large-scale compartmentalised genome-scale metabolic model, Potato-GEM. Apart from a large-scale reconstruction of primary metabolism, the model includes the full known potato secondary metabolism, spanning over 600 reactions that facilitate the biosynthesis of 182 distinct potato secondary metabolites. Constraint-based modelling identifies that the activation of the largest amount of secondary (defence) pathways occurs at a decrease of the relative growth rate of potato leaf, due to the costs incurred by defence. We then obtain transcriptomics data from experiments exposing potato leaves to two biotic stress scenarios, a herbivore and a viral pathogen, and apply it as constraints to produce condition-specific models. We show that these models recapitulate experimentally observed decreases in relative growth rates under treatment, enabling us to pinpoint the metabolic rewiring underlying growth-defence trade-offs. Potato-GEM thus presents a useful resource to study and broaden our understanding of potato and general plant defence responses under stress conditions.
Employing Artificial Neural Networks for Optimal Storage and Facile Sharing of Molecular Dynamics Simulation Trajectories
Authors: Wasim Abdul , Schäfer Lars V. , Mondal Jagannath 
Published: September 2024

AbstractWith the remarkable stride in computing power and advances in Molecular Dynamics simulation programs, a crucial challenge of storing and sharing large biomolecular simulation datasets has emerged. By leveraging AutoEncoders, a type of artificial neural network, we developed a method to compress MD trajectories into significantly smaller latent spaces. Our method can save upto 98% in disk space compared to XTC, a highly compressed trajectory format from the widely used MD program package GROMACS, thus facilitating easier storage and sharing of simulation trajectories. Atomic coordinates are very accurately reconstructed from compressed data. The method was tested across a variety of biomolecular systems, including folded proteins, intrinsically disordered proteins (IDPs), and protein-ligand complexes, showing consistent accuracy in reconstruction. Notably, the compression efficiency was particularly beneficial for larger systems. This approach enables the scientific community to more efficiently store and share large-scale biomolecular simulation data, potentially enhancing collaborative research efforts. The workflow, termed “compressTraj”, is implemented in PyTorch and is publicly available athttps://github.com/SerpentByte/compressTrajfor use, offering a practical solution for managing the growing volumes of data generated in computational biomolecular studies.
Unexpected absence of a multiple-queen supergene haplotype from supercolonial populations ofFormicaants
Authors: Lagunas-Robles German , Alam Zul , Brelsford Alan 
Published: September 2024

AbstractAnts exhibit many complex social organization strategies. One particularly elaborate strategy is supercoloniality, in which a colony consists of many interconnected nests (=polydomy) with many queens (=polygyny). In many species ofFormicaants, an ancient queen number supergene determines whether a colony is monogyne (=headed by single queen) or polygyne. The presence of the rearrangedPhaplotype typically leads colonies to be polygyne. However, the presence and function of this supergene polymorphism have not been examined in supercolonial populations. Here, we use genomic data from species in theFormica rufagroup to determine whether thePhaplotype leads to supercoloniality. In aFormica paralugubrispopulation, we find that nests are polygyne, despite the absence of thePhaplotype in workers. We find spatial genetic ancestry patterns in nests consistent with supercolonial organization. Additionally, we find that thePhaplotype is also absent in workers from supercolonialFormica aquilonia, andFormica aquiloniaxpolyctenahybrid populations, but is present in someFormica polyctenaworkers. We conclude that thePhaplotype is not necessary for supercoloniality in theFormica rufagroup, despite its longstanding association with non-supercolonial polygyny across theFormicagenus.
High Throughput Meta-analysis of Antimicrobial Peptides for Characterizing Class Specific Therapeutic Candidates: Anin-silicoApproach
Authors: Pandey Anwesh , Lenin Raji Rajesh , Patiyal Sumeet , Agrawal Piyush 
Published: September 2024

AbstractThe increasing incidence of antimicrobial resistance (AMR) is becoming a serious concern worldwide and requires newer drugs. Recent evidence has shown growing interest in developing peptide-based therapeutics to tackle AMR. In the current study, we performed a meta-analysis of nearly 8.6 million predicted antimicrobial peptides (AMPs) and assessed their antibacterial, antiviral, and antifungal activity. We created high-quality, class-specific datasets and performed several analyses, including amino acid composition, motif preference, physiochemical properties, etc. We observed significant differences in the residue composition, charge, molecular weight, pI value, and instability index of peptides among 3 AMP classes. We further developed multiple machine learning models to predict peptide activity using the dataset. Our Extratree model developed using composition-based features achieved the highest AUROC of 0.98 for antibacterial peptide (ABP), 0.99 for antiviral peptide (AVP), and 0.99 for antifungal peptide (AFP) prediction when tested on an independent dataset. Subsequent filtering of peptides based on moonlighting properties (toxicity, allergenicity, cell-penetrating ability, half-life, and secondary structure) yielded a list of peptides that exhibit substantial therapeutic potential. We further selected the top 10 peptides in each category based on their half-lives, predicted their 3D structures using ColabFold, a feature built into ChimeraX1.8 software, and used HDock to perform molecular docking analysis with a pathogenic protein selected from an organism in each class. Docking studies demonstrated strong interaction between peptides and proteins, and based on free energy, we ranked the peptides. Overall, we have put forth class-specific peptides with high therapeutic potential based on rigorous meta-analysis encompassing ∼8.6 million AMPs.
Climate Change and Malaria: A Call for Robust Analytics
Authors: Laydon Daniel J , Smith David L , Chakradeo Kaustubh , Khurana Mark P , Okiring Jaffer , Duchene David A , Bhatt Samir 
Published: September 2024

AbstractMosquito ecology and behavior and malaria parasite development display marked sensitivity to weather, in particular to temperature and precipitation. Therefore, climate change is expected to profoundly affect malaria epidemiology in its transmission, spatiotemporal distribution and consequent disease burden. However, malaria transmission is also complicated by other factors (e.g. urbanization, socioeconomic development, genetics, drug resistance) which together constitute a highly complex, dynamical system, where the influence of any single factor can be masked by others.In this study, we therefore aim to re-evaluate the evidence underlying the widespread belief that climate change will increase worldwide malaria transmission. We review two broad types of study that have contributed to this evidence-base: i) studies that project changes in transmission due to inferred relationships between environmental and mosquito entomology, and ii) regression-based studies that look for associations between environmental variables and malaria prevalence. We then employ a simple statistical model to show that environmental variables alone do not account for the observed spatiotemporal variation in malaria prevalence.Our review raises several concerns about the robustness of the analyses used for advocacy around climate change and malaria. We find that, while climate change’s effect on malaria is highly plausible, empirical evidence is much less certain. Future research on climate change and malaria must become integrated into malaria control programs, and understood in context as one factor among many. Our work outlines gaps in modelling that we believe are priorities for future research.
ArabidopsisAtGELP53 modulates polysaccharide acetylation and defense response through oligosaccharide-mediated signaling
Authors: Rastogi Lavi , Hussain Muhammad-Moazzam , Tyagi Shivangi , Kabyashree Kristi , Kharbanda Naman , Maiti Tushar Kanti , Krishnan Vengadesan , Jha Gopaljee , Voxeur Aline , Pawar Prashant Anupama-Mohan 
Published: September 2024

ABSTRACTO-acetylation is a crucial substitution found in hemicelluloses and pectin which are necessary for maintaining the flexibility and structural integrity of the cell. A balanced polysaccharideO-acetylation level is maintained by cell wall acetyl transferases and esterases present in different cell organelles. Specifically, the role of esterases in cell wall acetylation metabolism is less explored. Therefore, we investigated the role ofAtGELP53 from the GELP family of esterases or lipases. Here, we show thatAtGELP53 is localized in the plasma membrane. Analysis ofAtGELP53 overexpressing independent transgenic lines revealed a decrease in xyloglucan acetylation, changes in other polysaccharide acetylation and alteration in cell wall composition. The series of elicitor-based, transcriptomic and proteomic analyses inAtGELP53 overexpressing lines suggested that oligosaccharide-mediated signalling activates the cell wall and defence-related genes primarily because of xyloglucan deacetylation. Furthermore,AtGELP53 overexpression plants showed resistance againstPseudomonas syringaeandRalstonia solanacearumthrough activation of elicitor-mediated defense response. Overall, our findings outline the role ofAtGELP53 in polysaccharide acetylation, cell wall remodelling and defense through the activation of plant cell wall integrity.
Negative Charges, Not Necessary Phosphorylation, are Required for Ligand Recognition by 14-3-3 Proteins
Authors: Kamayirese Seraphine , Hansen Laura A. , Lovas Sándor 
Published: September 2024

AbstractProtein-protein interactions involving 14-3-3 proteins regulate various cellular activities in normal and pathological conditions. These interactions have mostly been reported to be phosphorylation-dependent, but the 14-3-3 proteins also interact with unphosphorylated proteins. In this work, we investigated whether phosphorylation is required, or, alternatively, whether negative charges are sufficient for 14-3-3ε binding. We substituted the pThr residue of pT(502-510) peptide by residues with varying number of negative charges, and investigated binding of the peptides to 14-3-3ε using MD simulations and biophysical methods. We demonstrated that at least one negative charge is required for the peptides to bind 14-3-3ε while phosphorylation is not necessary, and that two negative charges are preferable for high affinity binding.
Metagenomic detection of Mimiviridae reads in upper respiratory tract samples of SARS-CoV-2 patients
Authors: Tomar Siddharth Singh , Khairnar Krishna 
Published: September 2024

AbstractThe upper respiratory tract (URT) virome is crucial in respiratory health and response to pathogens. While common respiratory viruses are well-studied, the presence and potential impact of giant DNA viruses, such as Mimiviridae, in the human URT remain underexplored. This study employed a whole genome metagenomics approach to profile the URT virome of 48 SARS-CoV-2-positive patients from central India. Mimiviridae reads were detected in two elderly male patients with severe acute respiratory infection (SARI) or influenza-like illness (ILI), contributing to 24% and 44% of the total virome in their samples. The dominant species wereAcanthamoeba polyphaga mimivirusandMoumouvirus. Although Mimiviridae are not traditionally associated with human respiratory infections, their presence in SARS-CoV-2 patients raises questions about their potential role in co-infections and disease severity, particularly in individuals with ongoing respiratory infections. These findings underscore the need to investigate further giant viruses’ clinical significance, transmission, and pathogenicity in humans. Future research should focus on their epidemiology and the development of improved diagnostic tools to assess their contribution to human health.
Glucagon-Like Peptide 1 Receptor Agonists and Cardiovascular Disease Risk: Findings from Real-World Data using AI-Powered Outcomes
Authors: Prakash Shivaani , Coleman Jeffrey , Steinfeldt Jakob 
Published: September 2024

ABSTRACTBackgroundThe SELECT trial showed cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in obese patients with cardiovascular disease; however, real-world data (RWD) on this benefit remain limited. This study used an artificial intelligence (AI)-generated algorithm and multimodal RWD to evaluate the impact of GLP-1 RAs on cardiovascular disease risk in a population of obese patients with and without preexisting cardiovascular disease.MethodsUsing data from the Dandelion Health RWD library, an Emulated SELECT Cohort was created to include obese patients similar to those in the SELECT trial, but with and without preexisting cardiovascular disease. An AI algorithm developed by Pheiron that used 12-lead electrocardiograms (ECGs) as a predictive biomarker for the risk of major adverse cardiovascular events (MACE) was validated and used to derive MACE risk scores for the Emulated SELECT Cohort. These outcomes were compared over time between patients who used GLP-1 RAs and non-users using inverse-probability weighted linear regression models, adjusting for key covariates.ResultsOut-of-sample validation showed high predictive accuracy of the AI algorithm, with ROC AUCs of 0.81 for myocardial infarction (MI) and 0.75 for stroke. Increased risk scores from the algorithm were correlated with higher MACE incidence in RWD. In the Emulated SELECT Cohort of 20,795 patients, GLP-1 RA use was associated with significant attenuation of MACE risk, with reductions observed in percentile risk score for MI (4%; p<0.001) and stroke (3.6%; p<0.001) per year of use. Differences in GLP-1 RA and non-GLP-1 users were evident as early as 1.7 years, with a 15-20% difference in absolute MACE risk scores between GLP-1 RA users and non-users observed by the end of the study.ConclusionAn AI algorithm using 12-lead ECGs accurately predicted MACE risk and could be used to model risk attenuation associated with GLP-1 RA use. Using this outcome, we find that GLP-1 RA use was associated with significant reductions in MI and stroke risk, in a broader population and within a shorter timeframe than the SELECT trial. These findings suggest potentially significant cardioprotective benefits of GLP-1 RAs in real-world settings and demonstrate a proof-of-concept for utilizing clinical AI to understand these benefits.
Public communication and outreach by mosquito programs in the United States
Authors: Thomas Nicole , Balanay Jo Anne G. , Shearman Sachiyo , Richards Stephanie L. 
Published: September 2024

AbstractBlood feeding female mosquitoes cause itchy welts and can transmit pathogens that cause diseases such as chikungunya, malaria, West Nile encephalitis, and Zika. Mosquito control programs conduct mosquito, pathogen, and epidemiological surveillance, carry out source reduction, treat mosquito habitats with larvicides or adulticides, and disseminate information to the public. Here, 100 organizations (e.g., private/public mosquito control programs, national professional mosquito/pest control associations) in the United States were asked to complete a survey (N=39 respondents) about their public communication and outreach efforts. Results indicate most programs (N=27, 69%) have dedicated personnel for public communication. A checklist was constructed to compare communication strategies between a subset of program websites and Facebook pages. Recommendations for improving public communication and outreach strategies for mosquito control programs are discussed.
The Gq/11 family of Gα subunits is necessary and sufficient for lower jaw development
Authors: Kanai Stanley M. , Garcia Chloe R. , Augustus MaCalia R. , Sharafeldeen Shujan A. , Brooks Elliott P. , Sucharov Juliana , Lencer Ezra S. , Nichols James T. , Clouthier David E. 
Published: September 2024

AbstractVertebrate jaw development is coordinated by highly conserved ligand-receptor systems such as the peptide ligand Endothelin 1 (Edn1) and Endothelin receptor type A (Ednra), which are required for patterning of lower jaw structures. The Edn1/Ednra signaling pathway establishes the identity of lower jaw progenitor cells by regulating expression of numerous patterning genes, but the intracellular signaling mechanisms linking receptor activation to gene regulation remain poorly understood. As a first step towards elucidating this mechanism, we examined the function of the Gq/11 family of Gα subunits in zebrafish using pharmacological inhibition and genetic ablation of Gq/11 activity and transgenic induction of a constitutively active Gq protein inedn1-/-embryos. Genetic loss of Gq/11 activity fully recapitulated theedn1-/-phenotype, with genes encoding G11 being most essential. Furthermore, inducing Gq activity inedn1-/-embryos not only restored Edn1/Ednra-dependent jaw structures and gene expression signatures but also caused homeosis of the upper jaw structure into a lower jaw-like structure. These results indicate that Gq/11 is necessary and sufficient to mediate the lower jaw patterning mechanism for Ednra in zebrafish.Summary statementGq/11 is the signaling mediator downstream of Endothelin 1 and Endothelin Receptor Type A that drives tissue patterning for all lower jaw structures in zebrafish.
Fine-TuningTAWAWA1-Mediated Panicle Architecture by Genome Editing of a Downstream Conserved Noncoding Sequence in Rice
Authors: Kuroha Takeshi , Lombardo Fabien , Iwasaki Watal M , Chechetka Svetlana , Kawahara Yoshihiro , Yoshida Akiko , Kyozuka Junko , Makino Takashi , Yoshida Hitoshi 
Published: September 2024

SummaryGenome editing is a promising tool to enhance plant breeding, particularly for the generation of practical quantitative traits. We focused on the rice yield-related geneTAWAWA1(TAW1) and produced various degrees of increased panicle branching phenotypes by modifying its downstream conserved noncoding sequence (CNS). Differential modification of two highly conserved regions containing putative repressive elements in this CNS caused transcriptional upregulation ofTAW1, resulting in diverse phenotypes.
Human Neural Organoid Microphysiological Systems Show the Building Blocks Necessary for Basic Learning and Memory
Authors: Alam El Din Dowlette-Mary , Moenkemoeller Leah , Loeffler Alon , Habibollahi Forough , Schenkman Jack , Mitra Amitav , van der Molen Tjitse , Ding Lixuan , Laird Jason , Schenke Maren , Johnson Erik C. , Kagan Brett J. , Hartung Thomas , Smirnova Lena 
Published: September 2024

SummaryBrain Microphysiological Systems including neural organoids derived from human induced pluripotent stem cells offer a unique lens to study the intricate workings of the human brain. This paper investigates the foundational elements of learning and memory in neural organoids, also known as Organoid Intelligence by quantifying immediate early gene expression, synaptic plasticity, neuronal network dynamics, and criticality to demonstrate the utility of these organoids in basic science research. Neural organoids showed synapse formation, glutamatergic and GABAergic receptor expression, immediate early gene expression basally and evoked, functional connectivity, criticality, and synaptic plasticity in response to theta-burst stimulation. In addition, pharmacological interventions on GABAergic and glutamatergic receptors, and input specific theta-burst stimulation further shed light on the capacity of neural organoids to mirror synaptic modulation and short-term potentiation, demonstrating their potential as tools for studying neurophysiological and neurological processes and informing therapeutic strategies for diseases.Graphical AbstractOverview of the main components of the experiments conducted. Figure created using BioRender.com.
Identification and comparison ofN-glycome profiles from common dietary protein ingredients
Authors: Bolino Matthew , Avcı İzzet , Kayili Hacı Mehmet , Duman Hatice , Salih Bekir , Karav Sercan , Frese Steven A. 
Published: September 2024

AbstractTheN-glycome profiles purified from dietary bovine whey, egg white, pea, soy protein isolates and a recently commercialized animal-free whey is described. Purified glycoproteins resulting from centrifugation and ethanol precipitation of protein powder supplements were treated with peptide-N-glycosidase F (PNGase F) to release protein-boundN-glycans. Once released from the protein,N-glycans were labeled by procainamide labeling, purified via cotton-hydrophilic interaction liquid chromatography (HILIC), and analyzed using HILIC high performance liquid chromatography equipped with a fluorescence detector and a quadrupole time-of-flight tandem mass spectrometry (HILIC-FLD-QTOF-MS/MS). A total of 33, 33, 10, and 10N-glycan structures were identified from bovine whey, egg, soy, and pea glycoprotein isolates, respectively. The type ofN-glycans per glycoprotein source were highly predictable, likely attributed to differences in biosynthetic glycosylation pathways. Mammalian glycoprotein sources favored a combination of complex and hybrid glycan configurations while the plant proteins were dominated by oligomannosidicN-glycans. Bovine whey glycoprotein isolate contained the most diverseN-glycans by monosaccharide composition as well as structure, while plant sources such as pea and soy glycoprotein isolates contained an overlap of oligomannosidicN-glycans. The results suggestN-glycan structure and composition is dependent on the host organism rather than protein sequence homology, likely driven by the differences inN-glycan biosynthetic pathways.