bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying microbial DNA in metagenomes improves microbial trait estimation
Authors: Eisenhofer Raphael , Alberdi Antton , Woodcroft Ben J. 
Published: June 2024

AbstractShotgun metagenomics is a powerful tool for studying the genomic traits of microbial community members, such as genome size, gene content, etc. While such traits can be used to better understand the ecology and evolution of microbial communities, the accuracy of their estimations can be critically influenced by both known and unknown factors. One factor that can bias trait estimations is the proportion of eukaryotic DNA in a metagenome, as some bioinformatic tools assume that all DNA reads in a metagenome are non-eukaryotic. Here, we help resolve a recent debate about the influence of eukaryotic DNA in the estimation of average genome size from a global soil sample dataset using a new bioinformatic tool. Contrary to what was assumed, our reanalysis of this dataset revealed that soil samples can contain a substantial proportion of eukaryotic DNA (∼38.8%), which severely inflated average genome size estimates. We report that correcting for this bias significantly improves the statistical support for the negative relationship between average bacterial genome size and soil pH. These results highlight that metagenomes can contain large quantities of eukaryotic DNA, and that new methods that correct for this can improve microbial trait estimation.
A first-principles geometric model for dynamics of motor-driven centrosomal asters
Authors: Young Yuan-Nan , Gomez Herrera Vicente , Huan Helena Z. , Farhadifar Reza , Shelley Michael J. 
Published: June 2024

AbstractThe centrosomal aster is a mobile and adaptable cellular organelle that exerts and transmits forces necessary for tasks such as nuclear migration and spindle positioning. Recent experimental and theoretical studies of nematode and human cells demonstrate that pulling forces on asters by cortically anchored force generators are dominant during such processes. Here we present a comprehensive investigation of a first-principles model of aster dynamics, the S-model (S for stoichiometry), based solely on such forces. The model evolves the astral centrosome position, a probability field of cell-surface motor occupancy by centrosomal microtubules (under an assumption of stoichiometric binding), and free boundaries of unattached, growing microtubules. We show how cell shape affects the stability of centering of the aster, and its transition to oscillations with increasing motor number. Seeking to understand observations in single-cell nematode embryos, we use highly accurate simulations to examine the nonlinear structures of the bifurcations, and demonstrate the importance of binding domain overlap to interpreting genetic perturbation experiments. We find a generally rich dynamical landscape, dependent upon cell shape, such as internal constant-velocity equatorial orbits of asters that can be seen as traveling wave solutions. Finally, we study the interactions of multiple asters which we demonstrate an effective mutual repulsion due to their competition for surface force generators. We find, amazingly, that centrosomes can relax onto the vertices of platonic and non-platonic solids, very closely mirroring the results of the classical Thomson problem for energy-minimizing configurations of electrons constrained to a sphere and interacting via repulsive Coulomb potentials. Our findings both explain experimental observations, providing insights into the mechanisms governing spindle positioning and cell division dynamics, and show the possibility of new nonlinear phenomena in cell biology.
The ABC transporter MsbA in a dozen environments
Authors: Hoffmann Lea , Baier Anika , Jorde Lara , Kamel Michael , Schäfer Jan-Hannes , Schnelle Kilian , Scholz Alischa , Shvarev Dmitry , Wong Jaslyn E. M. M. , Parey Kristian , Januliene Dovile , Moeller Arne 
Published: June 2024

AbstractHigh-resolution structure determination of membrane proteins typically requires isolation from the native lipid bilayer and reconstitution into artificial membrane mimics. For this purpose, numerous detergents, amphipols, polymers and membrane scaffold proteins are available. The choice of the specific membrane substitute can strongly affect the protein’s specific activity, stability and conformational spectrum, potentially leading to errors or misinterpretation during analysis. The bacterial ATP-binding cassette transporter MsbA is a prominent example of such environment-specific bias, resulting in apparent conformational and activity responses.Here, we present a systematic analysis of the conformational spectrum of MsbA, stabilized in a dozen environments, using cryo-EM. Our data show pronounced structural feedback of the ABC transporter to the respective membrane mimetics. Detergents generally favour a conformation with wide separation of the nucleotide-binding domains, while nanodiscs induce the narrow conformation. Notably, only three of the dozen tested environments allow MsbA to sample the functional conformational spectrum, enabling full movement of the nucleotide-binding domains between narrow and wide inward-facing conformations. We expect this study to serve as a blueprint for other membrane proteins, even where the structural reaction to the hydrophobic environment is not directly visible but still critical for the proteins’ function.
Functional stability despite high taxonomic turnover characterizes the Ulva microbiome across a 2,000 km salinity gradient
Authors: van der Loos Luna M. , Steinhagen Sophie , Stock Willem , Weinberger Florian , D’hondt Sofie , Willems Anne , De Clerck Olivier 
Published: June 2024

AbstractThe green seaweed Ulva depends on its associated bacteria for morphogenesis and is an important model to study algal-bacterial interactions. Ulva-associated bacteria exhibit high turnover across environmental gradients, leading to the hypothesis that bacteria contribute to the acclimation potential of the host. Yet little is known about the variation in the functional profile of Ulva-associated bacteria in relation to environmental changes. To test which microbial functions shift alongside a strong environmental gradient, we analysed microbial communities of 91 Ulva samples across a 2,000 km Atlantic–Baltic Sea salinity gradient using metagenomic sequencing. Metabolic reconstruction of 639 metagenome-assembled genomes revealed widespread potential for carbon, sulphur, nitrogen, and vitamin metabolism, including amino acid and vitamin B biosynthesis. While salinity explained 70% of taxonomic variation, it only accounted for 17% of functional variation, indicating extensive functional stability. The limited variation was attributed to typical high-salinity bacteria exhibiting enrichment in genes for thiamine, pyridoxal, and betaine biosynthesis. These metabolic modules likely contribute to oxidative stress mitigation, cellular osmotic homeostasis, and membrane stabilization in response to salinity variations. Our results emphasise the importance of functional profiling to understand the seaweed holobiont and its collective response to environmental change.
Substrate Trapping in Polyketide Synthase Thioesterase Domains: Structural Basis for Macrolactone Formation
Authors: McCullough Tyler M. , Choudhary Vishakha , Akey David L. , Skiba Meredith A. , Bernard Steffen M. , Kittendorf Jeffrey D. , Schmidt Jennifer J. , Sherman David H. , Smith Janet L. 
Published: June 2024

AbstractEmerging antibiotic resistance requires continual improvement in the arsenal of antimicrobial drugs, especially the critical macrolide antibiotics. Formation of the macrolactone scaffold of these polyketide natural products is catalyzed by a modular polyketide synthase (PKS) thioesterase (TE). The TE accepts a linear polyketide substrate from the termina PKS acyl carrier protein to generate an acyl-enzyme adduct that is resolved by attack of a substrate hydroxyl group to form the macrolactone. Our limited mechanistic understanding of TE selectivity for a substrate nucleophile and/or water has hampered development of TEs as biocatalysts that accommodate a variety of natural and non-natural substrates. To understand how TEs direct the substrate nucleophile for macrolactone formation, acyl-enzyme intermediates were trapped as stable amides by substituting the natural serine OH with an amino group. Incorporation of the unnatural amino acid, 1,3-diaminopropionic acid (DAP), was tested with five PKS TEs. DAP-modified TEs (TEDAP) from the pikromycin and erythromycin pathways were purified and tested with six full-length polyketide intermediates from three pathways. The erythromycin TE had permissive substrate selectivity, whereas the pikromycin TE was selective for its native hexaketide and heptaketide substrates. In a crystal structure of a native substrate trapped in pikromycin TEDAP, the linear heptaketide was curled in the active site with the nucleophilic hydroxyl group positioned 4 Å from the amide-enzyme linkage. The curled heptaketide displayed remarkable shape complementarity with the TE acyl cavity. The strikingly different shapes of acyl cavities in TEs of known structure, including those reported here for juvenimicin, tylosin and fluvirucin biosynthesis, provide new insights to facilitate TE engineering and optimization.
The translocation assembly module (TAM) catalyzes the assembly of bacterial outer membrane proteinsin vitro
Authors: Wang Xu , Nyenhuis Sarah B. , Bernstein Harris D. 
Published: June 2024

ABSTRACTThe bacterial translocationassemblymodule (TAM) contains an outer membrane protein (OMP) (TamA) and an elongated periplasmic protein that is anchored to the inner membrane by a single α helix (TamB). TAM has been proposed to play a critical role in the assembly of a small subset of OMPs produced by Proteobacteria based on experiments conductedin vivousingtamAand/ortamBdeletion or mutant strains andin vitrousing biophysical methods. Recent genetic experiments, however, have strongly suggested that TAM promotes phospholipid homeostasis. To test the idea that TAM catalyzes OMP assembly directly, we examined the function of the purifiedE. colicomplexin vitroafter reconstituting it into proteoliposomes. Remarkably, we find that TAM catalyzes the assembly of four model OMPs nearly as well as the β-barrelassemblymachinery (BAM), a universal heterooligomer that contains a TamA homolog (BamA) and that catalyzes the assembly of almost allE. coliOMPs. Consistent with previous results, both TamA and TamB are required for significant TAM activity. Our results provide strong evidence that although their peripheral subunits are unrelated, both BAM and TAM function as independent OMP insertases. Furthermore, our study describes a new method to gain insights into TAM function.
Excess folic acid exposure increases uracil misincorporation into DNA in a tissue-specific manner in a mouse model of reduced methionine synthase expression
Authors: Heyden Katarina E. , Malysheva Olga V. , MacFarlane Amanda J. , Brody Lawrence C. , Field Martha S. 
Published: June 2024

AbstractBackgroundFolate and vitamin B12 (B12) are cofactors in folate-mediated one-carbon metabolism (FOCM), a metabolic network that supports synthesis of nucleotides (including thymidylate, or dTMP) and methionine. FOCM impairments such as a deficiency or imbalance of cofactors can perturb dTMP synthesis, causing uracil misincorporation into DNA.ObjectiveThe purpose of this study was to determine how reduced expression of the B12-dependent enzyme methionine synthase (MTR) and excess dietary folic acid interact to affect folate distribution and markers of genome stability in mouse tissues.MethodsHeterozygousMtrknockout mice (Mtr+/-) model the FOCM-specific effects of B12 deficiency. Folate accumulation and vitamer distribution, genomic uracil levels, and phosphorylated histone γH2AX immunostaining were measured in maleMtr+/+andMtr+/−mice weaned to either a folate-sufficient control (C) diet (2 mg/kg folic acid) or a high folic acid (HFA) diet (20 mg/kg folic acid) for 7 weeks.ResultsExposure to the HFA diet led to tissue-specific patterns of folate accumulation, with plasma, colon, kidney, and skeletal muscle exhibiting increased folate concentrations compared to control. Liver total folate did not differ. Though unmetabolized folic acid (UMFA) increased 10-fold in mouse plasma with HFA diet, UMFA accounted for less than 0.2% of total folate in liver and colon tissue. Exposure to HFA diet resulted in a shift in folate distribution in colon tissue with higher 5-methyl-THF and lower formyl-THF than in control mice.Mtrheterozygosity did not impact folate accumulation or distribution in any tissue. Mice on HFA diet exhibited higher uracil in genomic DNA and γH2AX foci in colon. Similar differences were not seen in liver.ConclusionsThis study demonstrates that folic acid, even when consumed at high doses, does not meaningfully accumulate in mouse tissues, although high-dose folic acid shifts folate distribution and increases uracil accumulation in genomic DNA in colon tissue.
Leveraging patients’ longitudinal data to improve the Hospital One-year Mortality Risk
Authors: Laribi Hakima , Raymond Nicolas , Taseen Ryeyan , Poenaru Dan , Vallières Martin 
Published: June 2024

AbstractPurposePredicting medium-term survival after admission is necessary for identifying end-of-life patients who may benefit from goals of care (GOC) discussions. Considering that several patients have multiple hospital admissions, this study leverages patients’ longitudinal data and information collected routinely at admission to predict the Hospital One-year Mortality Risk.MethodsWe propose an Ensemble Long Short-term Memory neural network (ELSTM) to predict one-year mortality using patients’ longitudinal records. The model was evaluated: (i) with only predictors reported upon admission (AdmDemo); and (ii) also with diagnoses available later during patients’ stay (AdmDemoDx). Using records of 123,646 patients with 250,812 hospitalizations from 2011-2021, our dataset was split into a learning set (2011-2017) to compare models with and without longitudinal information using nested cross-validation, and a holdout set (2017-2021) to assess clinical utility towards GOC discussions.ResultsThe ELSTM achieved a significant increase in predictive performance using longitudinal information (p-value < 0.05) for both the AdmDemo and AdmDemoDx predictors. For randomly selected hospitalizations in the holdout set, the ELSTM showed: (i) AUROCs of 0.83 (AdmDemo) and 0.87 (AdmDemoDx); and (ii) superior decision-making properties, notably with an increase in precision from 0.25 for the standard process to 0.28 (AdmDemo) and 0.36 (AdmDemoDx). Feature importance analysis confirmed that the utility of the longitudinal information increases with the number of patient hospitalizations.ConclusionIntegrating patients’ longitudinal data provides better insights into the severity of illness and the overall patient condition, in particular when limited information is available during their stay.
Optimal disease surveillance with graph-based Active Learning
Authors: Tsui Joseph L.-H. , Zhang Mengyan , Sambaturu Prathyush , Busch-Moreno Simon , Suchard Marc A. , Pybus Oliver G. , Flaxman Seth , Semenova Elizaveta , Kraemer Moritz U. G. 
Published: June 2024

AbstractTracking the spread of emerging pathogens is critical to the design of timely and effective public health responses. Policymakers face the challenge of allocating finite resources for testing and surveillance across locations, with the goal of maximising the information obtained about the underlying trends in prevalence and incidence. We model this decision-making process as an iterative node classification problem on an undirected and unweighted graph, in which nodes represent locations and edges represent movement of infectious agents among them. To begin, a single node is randomly selected for testing and determined to be either infected or uninfected. Test feedback is then used to update estimates of the probability of unobserved nodes being infected and to inform the selection of nodes for testing at the next iterations, until a certain resource budget is exhausted. Using this framework we evaluate and compare the performance of previously developed Active Learning policies, including node-entropy and Bayesian Active Learning by Disagreement. We explore the performance of these policies under different outbreak scenarios using simulated outbreaks on both synthetic and empirical networks. Further, we propose a novel policy that considers the distance-weighted average entropy of infection predictions among the neighbours of each candidate node. Our proposed policy outperforms existing ones in most outbreak scenarios, leading to a reduction in the number of tests required to achieve a certain predictive accuracy. Our findings could inform the design of cost-effective surveillance strategies for emerging and endemic pathogens, and reduce the uncertainties associated with early risk assessments in resource-constrained situations.
Direct evidence of real-space pairing in
BaBiO3
Authors: Menushenkov A. P. , Ivanov A. , Neverov V. , Lukyanov A. , Krasavin A. , Yastrebtsev A. A. , Kovalev I. A. , Zhumagulov Y. , Kuznetsov A. V. , Popov V. , Tselikov G. , Shchetinin I. , Krymskaya O. , Yaroslavtsev A. , Carley R. , Mercadier L. , Yin Z. , Parchenko S. , Hoang L. P. , Ghodrati N. , Kim Y. Y. , Schlappa J. , Izquierdo M. , Molodtsov S. , Scherz A. 
Published: June 2024

The parent compound BaBiO3 of bismuthate high-temperature superconductors (HTSCs) BaBi(Pb)O3 and Ba(K)BiO3 with perovskitelike structure exhibits unusual electronic and structural properties, which can be satisfactorily explained if we assume that all charge carriers are in the paired state. However, the prior experiments and the first-principle calculations only indirectly indicate the existence of paired charge carriers in BaBiO3. In this work, we report the direct evidence of initially paired electrons and holes in the upper antibonding Bi 6s−O2pσ* orbital of the neighboring octahedral complexes in the ground state of BaBiO3 using the time-resolved x-ray absorption spectroscopy (XAS) to monitor the electron dynamics after the femtosecond resonant 633 nm laser excitation. We observe strong changes in the oxygen K-edge XAS preedge region, defined by the Bi6s−O2pσ* orbitals. We interpret them as a fast (≤0.3 ps) breaking of charge carrier pairs and slower (0.3–0.8 ps) lattice rearrangement from the distorted monoclinic structure into the new metastable state with a cubic lattice, which persists at least up to 60 ps after the excitation. Analysis of the intermediate state at the fast excitation shows that the bond disproportionation and monoclinic distortion of BaBiO3 structure are energetically favorable due to the charge carrier pairing. Thus the compound BaBiO3 forms a new quantum state that we define as a local pair density wave. Taking into account a large number of similarities between bismuthate and cuprate high-temperature superconductors, we believe that our work will give a new impetus to understanding the nature of superconductivity in perovskite HTSCs.

Published by the American Physical Society
2024
Contrasting approaches to very high capacity network regulation and policy: a comparative analysis of France, Portugal, Spain and the UK (2008–2020)
Authors: Manica Luis 
Published: June 2024

Purpose
The purpose of this paper is to examine the factors that may have contributed to different levels of very high-capacity network (VHCN) coverage, with a particular focus on the role of regulation and State aid.

Design/methodology/approach
A comparative empirical study based on multiple case studies was conducted in France, Portugal, Spain and the UK.

Findings
Although France, Portugal and Spain initially adopted similar regulatory strategies for VHCN deployment, the outcomes differed significantly. The UK, with a more demanding regulation, achieved a residual coverage. This study highlights the importance of the regulatory approach to VHCN access in balancing private and public investment and emphasizes the importance of State aid in the policy agenda for nationwide VHCN deployment projects.

Research limitations/implications
Research on complex phenomena, such as the impact of regulation on investment or the effectiveness of State aid procedures, may focus on specific events to the detriment of others, which could bias the results.

Practical implications
The findings of this study provide insights for policymakers involved in State aid decisions and regulators by understanding the importance of timely State aid interventions, efficient governance and the impact of regulation on investment incentives.

Originality/value
This paper extends the literature on the impact of regulation on investment incentives and State aid as a tool to complement private investment for VHCN deployment through in-depth case studies.
The economic impacts of the European Union’s Carbon Border Adjustment Mechanism on developing countries: the case of Vietnam
Authors: Chu Hoang Long , Do Nam Thang , Nguyen Loan , Le Lien , Ho Quoc Anh , Dang Khoi , Ta Minh Anh 
Published: June 2024

PurposeThis paper aims to assess the economic impacts of the European Union’s Carbon Border Adjustment Mechanism (CBAM) on Vietnam.Design/methodology/approachWe constructed a general equilibrium model to assess the economic impacts of the CBAM on the macroeconomic indicators of Vietnam. We also constructed a generic partial equilibrium model to provide a zoomed-in view of the impact on each group of CBAM-targeted commodities, which is not possible in the general equilibrium model. Both the general equilibrium and the partial equilibrium models were calibrated with publicly available data and a high number of value sets of hyperparameters to estimate the variations of the estimated impacts.FindingsThe results suggest that the current form of the EU’s CBAM is unlikely to produce substantial effects on the overall economy of Vietnam, mainly because the commodities affected by it represent a small portion of Vietnam’s exports. However, at the sectoral level, the CBAM can reduce production outputs and export values of steel, aluminium, and cement.Social implicationsThe CBAM by itself may not lead to significant decreases in greenhouse gas emissions, but it could provide a rationale for implementing carbon pricing strategies, which might result in more significant economic effects and help in reducing greenhouse gas emissions. This highlights the necessity of supplementary policies to tackle global climate change.Originality/valueWe constructed economic models to evaluate the impacts of the European Union’s Carbon Border Adjustment Mechanism on Vietnam, both at the macroeconomic level and zooming in on directly impacted groups of commodities.