bluuebunny/crossref_metadata_2025 huggingface dataset:
EuDockScore: euclidean graph neural networks for scoring protein-protein interfaces
Authors: McFee Matthew , Kim Jisun , Kim Philip M.
Published: June 2024

Protein-protein interactions are essential for a variety of biological phenomena including mediating bio-chemical reactions, cell signaling, and the immune response. Proteins seek to form interfaces which reduce overall system energy. Although determination of single polypeptide chain protein structures has been revolutionized by deep learning techniques, complex prediction has still not been perfected. Additionally, experimentally determining structures is incredibly resource and time expensive. An alternative is the technique of computational docking, which takes the solved individual structures of proteins to produce candidate interfaces (decoys). Decoys are then scored using a mathematical function that predicts the energy of the system, know as a scoring functions. Beyond docking, scoring functions are a critical component of assessing structures produced by many protein generative models. Scoring models are also used as a final filtering in many generative deep learning models including those that generate antibody binders, and those which perform docking. In this work we present improved scoring functions for protein-protein interactions which utilizes cutting-edge euclidean graph neural network architectures, to assess protein-protein interfaces. These euclidean docking score models are known as EuDockScore, and EuDockScore-Ab with the latter being antibody-antigen dock specific. Finally, we provided EuDockScore-AFM a model trained on antibody-antigen outputs from AlphaFold-Multimer which proves useful in re-ranking large numbers of AlphaFold-Multimer outputs. The code for these models is available athttps://gitlab.com/mcfeemat/eudockscore.
A structure-guided approach to predict MHC-I restriction of T cell receptors for public antigens
Authors: Gupta Sagar , Sgourakis Nikolaos G.
Published: June 2024

Peptides presented by class I major histocompatibility complex (MHC-I) proteins provide biomarkers for therapeutic targeting using T cell receptors (TCRs), TCR-mimicking antibodies (TMAs), or other engineered protein binders. Despite the extreme sequence diversity of the Human Leucocyte Antigen (HLA, the human MHC), a given TCR or TMA is restricted to recognize epitopic peptides in the context of a limited set of different HLA allotypes. Here, guided by our analysis of 96 TCR:pHLA complex structures in the Protein Data Bank (PDB), we identify TCR contact residues and classify 148 common HLA allotypes into T-cell cross-reactivity groups (T-CREGs) on the basis of their interaction surface features. Insights from our work have actionable value for resolving MHC-I restriction of TCRs, guiding therapeutic expansion of existing therapies, and informing the selection of peptide targets for forthcoming immunotherapy modalities.
Plant cold acclimation and its impact on sensitivity of carbohydrate metabolism
Authors: Adler Stephan O. , Kitashova Anastasia , Bulović Ana , Nägele Thomas , Klipp Edda
Published: June 2024

The ability to acclimate to changing environmental conditions is essential for the fitness and survival of plants. Not only are seasonal differences challenging for plants growing in different habitats but, facing climate change, the likelihood of encountering extreme weather events increases. In order to better assess and respond to associated future challenges and risks it is important to understand the processes happening during acclimation. Previous studies of acclimation processes ofArabidopsis thalianato changes in temperature and light conditions have revealed a multigenic trait comprising and affecting multiple layers of molecular organization. Here, a combination of experimental and computational methods was applied to study the effects of changing light intensities during cold acclimation on the central carbon metabolism ofArabidopsis thalianaleaves. Mathematical modeling, simulation and sensitivity analysis predicted an important role of hexose phosphate balance for stabilization of photosynthetic CO2fixation. Experimental validation revealed a profound effect of temperature on the sensitivity of carbohydrate metabolism.
FDA-approved PDE4 inhibitors reduce the dominant toxicity of ALS–FTD-associatedCHCHD10S59L
Authors: Maitra Swati , Baek Minwoo , Choe Yun-Jeong , Kim Nam Chul
Published: June 2024

Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10(CHCHD10) have been identified as a genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia(ALS-FTD). In our previous studies using in vivoDrosophilamodel expressing C2C10HS81L, and human cell models expressing CHCHD10S59L, we have identified that the PINK1/Parkin pathway is activated and causes cellular toxicity. Furthermore, we demonstrated that pseudo-substrate inhibitors for PINK1 and mitofusin2 agonists mitigated the cellular toxicity of CHCHD10S59L. Evidences usingin vitro/ in vivogenetic and chemical tools indicate that inhibiting PINK1 would be the most promising treatment for CHCHD10S59L-induced diseases. Therefore, we have investigated cellular pathways that can modulate the PINK1/Parkin pathway and reduce CHCHD10S59L-induced cytotoxicity. Here, we report that FDA-approved PDE4 inhibitors reduced CHCHD10S59L-induced morphological and functional mitochondrial defects in human cells and anin vivo Drosophilamodel expressing C2C10HS81L. Multiple PDE4 inhibitors decreased PINK1 accumulation and downstream mitophagy induced by CHCHD10S59L. These findings suggest that PDE4 inhibitors currently available in the market may be repositioned to treat CHCHD10S59L-induced ALS-FTD and possibly other related diseases.
Spatial localization of hippocampal replay requires dopamine signaling
Authors: Kleinman Matthew R. , Foster David J.
Published: June 2024

Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of episodic memory, but whether replays depend on the brain’s reward or novelty signals is unknown. Here we combined chemogenetic silencing of dopamine neurons in ventral tegmental area (VTA) and simultaneous electrophysiological recordings in dorsal hippocampal CA1, in freely behaving male rats experiencing changes to reward magnitude and environmental novelty. Surprisingly, VTA silencing did not prevent ripple increases where reward was increased, but caused dramatic, aberrant ripple increases where reward was unchanged. These increases were associated with increased reverse-ordered replays. On familiar tracks this effect disappeared, and ripples tracked reward prediction error, indicating that non-VTA reward signals were sufficient to direct replay. Our results reveal a novel dependence of hippocampal replay on dopamine, and a role for a VTA-independent reward prediction error signal that is reliable only in familiar environments.
An updated compendium and reevaluation of the evidence for nuclear transcription factor occupancy over the mitochondrial genome
Authors: Marinov Georgi K. , Ramalingam Vivekanandan , Greenleaf William J. , Kundaje Anshul
Published: June 2024

In most eukaryotes, mitochondrial organelles contain their own genome, usually circular, which is the remnant of the genome of the ancestral bacterial endosymbiont that gave rise to modern mitochondria. Mitochondrial genomes are dramatically reduced in their gene content due to the process of endosymbiotic gene transfer to the nucleus; as a result most mitochondrial proteins are encoded in the nucleus and imported into mitochondria. This includes the components of the dedicated mitochondrial transcription and replication systems and regulatory factors, which are entirely distinct from the information processing systems in the nucleus. However, since the 1990s several nuclear transcription factors have been reported to act in mitochondria, and previously we identified 8 human and 3 mouse transcription factors (TFs) with strong localized enrichment over the mitochondrial genome using ChIP-seq (Chromatin Immunoprecipitation) datasets from the second phase of the ENCODE (Encyclopedia of DNA Elements) Project Consortium. Here, we analyze the greatly expanded in the intervening decade ENCODE compendium of TF ChIP-seq datasets (a total of 6,153 ChIP experiments for 942 proteins, of which 763 are sequence-specific TFs) combined with interpretative deep learning models of TF occupancy to create a comprehensive compendium of nuclear TFs that show evidence of association with the mitochondrial genome. We find some evidence for chrM occupancy for 50 nuclear TFs and two other proteins, with bZIP TFs emerging as most likely to be playing a role in mitochondria. However, we also observe that in cases where the same TF has been assayed with multiple antibodies and ChIP protocols, evidence for its chrM occupancy is not always reproducible. In the light of these findings, we discuss the evidential criteria for establishing chrM occupancy and reevaluate the overall compendium of putative mitochondrial-acting nuclear TFs.
MetaPathways v3.5: Modularity and Scalability Improvements for Pathway Inference from Environmental Genomes
Authors: McLaughlin Ryan J. , Liu Tony X. , Altman Tomer , Nallan Aditi N. , Hahn Aria S. , Anstett Julia , Morgan-Lang Connor , Konwar Kishori M. , Hallam Steven J.
Published: June 2024

Over the past decade MetaPathwayshas advanced as a modular pipeline for constructing environmental pathway genome databases (ePGDBs), increasing our understanding of microbial metabolism at the individual, population and community levels of biological organization. With this release, we have addressed several user experience issues related to installation, module integration, and database management. With a refactored code base, MetaPathwaysv3.5 enhances the user experience through streamlined installation via package indexes or containers, refined modules, and interface upgrades. It boasts updated algorithm support for sequence feature prediction, annotation, metabolic inference, and coverage metrics including genome resolved metagenomes. Tested and refined on synthetic datasets, MetaPathwaysv3.5 demonstrates improved performance and usability; facilitating more in-depth exploration of microbial interactions and metabolic functions in environmental genomes that scales with con-temporary sequencing throughput.

Availability and Implementation

MetaPathwaysv3.5 is availableviaAnaconda, Docker, and Apptainer. The source code is available on BitBucket:https://bitbucket.org/BCB2/metapathways/The documentation is available via ReadTheDocs:https://metapathways.readthedocs.io

Contact

shallam@mail.ubc.ca
Convergent evolution of type I antifreeze proteins from four different progenitors in response to global cooling
Authors: Graham Laurie A. , Davies Peter L.
Published: June 2024

The alanine-rich, alpha-helical type I antifreeze proteins (AFPs) in fishes are thought to have arisen independently in the last 30 ma on at least four occasions. This hypothesis has recently been proven for the flounder and sculpin AFPs that both originated by gene duplication and divergence followed by substantial gene copy number expansion. Here we have examined the origins of the cunner (wrasse) and snailfish (liparid) AFPs. The cunner AFP has arisen by a similar route from the duplication and divergence of a GIMAP gene. The coding region for this AFP stems from an alanine-rich region flanking the GTPase domain of GIMAPa. The AFP gene has remained in the GIMAP gene locus and undergone amplification there along with some GIMAPa genes. The AFP gene originated after the cunner diverged from the common ancestor to the closely related spotty and ballan wrasses that have a similar gene synteny but are completely lacking the AFP genes. Snailfish AFPs have also recently evolved because they are confined to a single genus of this family. In these AFP-producing species the AFP locus does not share any similarity to functional genes. Instead, it is replete with repetitive DNAs and transposons several stretches of which could code for tracts of alanine with a dominant codon (GCC) that matches the bias seen in the AFP genes. All four known instances of type I AFPs occurring in fishes are independent evolutionary events that happened soon after the onset of northern hemisphere Cenozoic glaciation events. Collectively they provide a remarkable example of convergent evolution to one AFP type.
Haptic perception is contingent to hemispaces, not to hands
Authors: Hartcher-O’Brien Jess , Terekhov Alexander V. , Hayward Vincent
Published: June 2024

Absract

It is known that human haptic perception is lateralised, for example, object shape is felt differently according to the hand used to explore objects. Here we show that it is not the hand but the hemispace in which the exploring hand is located that determines differences in perception. This finding implies that our lateralised somatosensory processing depends on hand localisation in space rather than on the hand itself.
Elucidating key determinants of engineered scFv antibody in MMP-9 binding using high throughput screening and machine learning
Authors: Kalantar Masoud , Kalanther Ifthichar , Kumar Sachin , Buxton Elham Khorasani , Raeeszadeh-Sarmazdeh Maryam
Published: June 2024

An imbalance in matrix metalloproteinase-9 (MMP-9) regulation can lead to numerous diseases, including neurological disorders, cancer, and pre-term labor. Engineering single-chain antibody fragments (scFvs) Targeting MMP-9 to develop novel therapeutics for such diseases is desirable. We screened a synthetic scFv antibody library displayed on the yeast surface for binding improvement to MMP-9 using FACS (fluorescent-activated cell sorting). The scFv antibody clones isolated after FACS showed improvement in binding to MMP-9 compared to the endogenous inhibitor. To understand molecular determinants of binding between engineered scFv antibody variants and MMP-9, next-generation DNA sequencing, and computational protein structure analysis were used. Additionally, a deep-learning language model was trained on the synthetic library to predict the binding of scFv variants using their CDR-H3 sequences.
Assessing the Stability of Photon-Counting CT: Insights from a Two-Year Longitudinal Study
Authors: Liu Leening P. , Pasyar Pouyan , Liu Fang , Cao Quy , Sandvold Olivia F. , Rybertt Martin V. , Sahbaee Pooyan , Shinohara Russell T. , Litt Harold I. , Noël Peter B.
Published: June 2024

Objective

Among the advancements in computed tomography (CT) technology, photon-counting computed tomography (PCCT) stands out as a significant innovation, providing superior spectral imaging capabilities while simultaneously reducing radiation exposure. Its long-term stability is important for clinical care, especially longitudinal studies, but is currently unknown. This study sets out to comprehensively analyze the long-term stability of a first-generation clinical PCCT scanner.

Methods

Over a two-year period, from November 2021 to November 2023, we conducted weekly identical experiments utilizing the same multi-energy CT protocol. Throughout this period, notable software and hardware modifications were meticulously recorded. Various tissue-mimicking inserts were scanned weekly to rigorously assess the stability of Hounsfield Units (HU) and image noise in Virtual Monochromatic Images (VMIs) and iodine density maps.

Results

Spectral results consistently demonstrated the quantitative stability of PCCT. VMIs exhibited stable HU values, such as variation in relative error for VMI 70 keV measuring 0.11% and 0.30% for single-source and dual-source modes, respectively. Similarly, noise levels remained stable with slight fluctuations linked to software changes for VMI 40 and 70 keV that corresponded to changes of 8 and 1 HU, respectively. Furthermore, iodine density quantification maintained stability and showed significant improvement with software and hardware changes, especially in dual-source mode with nominal errors decreasing from 1.44 to 0.03 mg/mL. Conclusion This study provides the first long-term reproducibility assessment of quantitative PCCT imaging, highlighting its potential for the clinical arena.

Key Points

Question:Photon-counting CT (PCCT) provides critical spectral imaging for improved diagnostic accuracy, but its long-term quantitative stability over time is still unknown.

Findings:The clinical PCCT system demonstrated stable Hounsfield Units (HU) and image noise over two years, ensuring reliable quantitative imaging and improving diagnostic accuracy.

Clinical Relevance:This study showcased the exceptional value of PCCT in diagnostic radiology, particularly for its application in longitudinal studies.
Deconvoluting synovial fluid molecular endotypes in knee osteoarthritis: primary results from the STEpUP OA Consortium
Authors: Perry T.A. , Deng Y. , Hulley P. , Maciewicz R.A. , Mitchelmore J. , Larsson S. , Gogain J. , Brachat S. , Struglics A. , Appleton C.T. , Kluzek S. , Arden N.K. , Price A.J. , Felson D. , Bondi L. , Kapoor M. , Lohmander L.S. , Welting T.J. , Walsh D.A. , Valdes A.M. ,   the STEpUP OA Consortium, Jostins-Dean L. , Watt F.E. , Tom B.D.M. , Vincent T.L.
Published: June 2024

Background

Osteoarthritis (OA) has a lifetime risk of over 40%, imposing a huge societal burden. Clinical variability suggests that it could be more than one disease.Synovial fluidTo detectEndotypes byUnbiasedProteomics in OA (STEpUP OA) was established to test the hypothesis that there are detectable distinct molecular endotypes in knee OA.

Methods

OA knee synovial fluid (SF) samples (N=1361) were from pre-existing OA cohorts with cross-sectional clinical (radiographic and pain) data. Samples were divided into Discovery (N = 708) and Replication (N=653) datasets. Proteomic analysis was performed using SomaScan V4.1 assay (6596 proteins). Unsupervised clustering was performed using k-means, assessed using the f(k) metric, with and without adjustments for potential confounders. Regression analyses were used to assess protein associations with radiographic (Kellgren and Lawrence) and knee pain (WOMAC pain), with and without stratification by body mass index (BMI) or biological sex. Adjustments were made for cohort (random intercept) or intracellular protein, using an intracellular protein score (IPS). Analyses were carried out in R according to a pre-published plan.

Results

No distinct SF molecular endotypes were identified in OA but two indistinct clusters were defined in non-IPS regressed data which were stable across subgroup analyses. Clustering was lost after IPS regression adjustment. Strong, replicable protein associations were observed with radiographic disease severity, which were retained after adjustment for cohort or IPS. Pathway analysis identified a strong “epithelial to mesenchymal transition (EMT)” pathway, and weaker associations with “angiogenesis”, “complement” and “coagulation”. The latter were variably lost after adjustment for BMI or biological sex. Associations with patient reported pain were weaker.

Conclusion

These data support knee OA as a biologically continuous disease in which disease severity is associated with a strong, robust, tissue remodelling signature. Subtle differences were found in pathways after stratification by BMI or sex.
Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis
Authors: Shearer Gregory C. , Block Robert C. , Huang Shue , Liu Linxi , Herrington David M. , Tsai Michael Y. , Tintle Nathan , O’Connell Timothy D.
Published: June 2024

Background

We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.g lipoxygenase, cytochrome p450, or cyclooxygenase (COX)) which mediate intracellular adaptive signaling.

Methods

Plasma phospholipid PUFA abundance at Exam 1 as mass percent EPA, DHA, and arachidonic acid (AA) from the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using pathway modeling to determine the association with time-dependent changes in left ventricular (LV) mass (LVM), end-diastolic LV volume (EDV), and end-systolic volume (ESV) measured by cardiac MRI at Exams 1 and 5. Ejection fraction (EF) and mass:volume (MV) were calculated posteriorly from the first three.

Results

2,877 subjects had available MRI data. Participants with low AA and EPA had accelerated age-dependent declines in LVM. Males with low AA and EPA also had accelerated declines in EDV, but among females there was no PUFA association with EDV declines and exam 5 EDV status was positively associated with AA. Both sexes had nearly the same positive association of AA with changes in ESV.

Conclusion

Plasma phospholipid AA and EPA are prospectively associated with indices of heart remodeling, including ventricular remodeling and performance. Combined AA and EPA scarcity was associated with the most accelerated age-related changes and exam 5 status, while the greatest benefits were found among participants with both PUFAs. This suggests that both PUFAs are required for optimal slowing of age-related declines in ventricular function.
Transition probabilities for dental caries in a school-based prevention program: A randomized clinical trial
Authors: Ruff Ryan Richard
Published: June 2024

Background

School-based caries prevention using silver diamine fluoride (SDF) has been shown to effectively prevent and control dental caries. To better inform program design and implementation, this paper estimated transition probabilities for dental caries in a school SDF program.

Methods

The CariedAway project was a pragmatic, cluster-randomized trial of school-based caries prevention interventions conducted in predominately low-income minority children. For children in CariedAway receiving SDF, transition probabilities were computed between sound, carious, and arrested states for 6-year molars using multistate Markov models. Subject-level transition probabilities over one- and two-year periods were then calculated by aggregating states of all 6-year molars and first and second bicuspids.

Results

A total of 7418 children were enrolled in CariedAway, of which 1352 met inclusion criteria for this study. Of eligible participants, the baseline prevalence of untreated decay was 29% and the prevalence of dental sealants was 8%. The probability of transitioning between sound and carious states in 6-year molars ranged from 0.0022 to 0.0074. At the subject-level, the sound to carious transition probabilities were 0.07 and 0.12 after one and two years, respectively. Once in a fully arrested state, the probability of remaining arrested was 0.72 and 0.60 after one and two years.

Conclusions

The overall probabilities of teeth remaining in diseased-free or arrested states was high after receiving silver diamine fluoride, although multiple applications might be needed for consistent caries arrest.
Testing effectiveness and implementation of a standardized approach to sexual dysfunction screening among adolescent and young adult-aged survivors of childhood cancer: A type I hybrid, mixed methods trial protocol
Authors: Demedis Jenna , Reedy Julia , Miller Kristen , Hu Junxiao , Klosky James L. , Holliman Brooke Dorsey , Peterson Pamela N. , Chow Eric J. , Studts Christina
Published: June 2024

Background

Approximately 20-50% of adolescent and young adult-aged childhood cancer survivors (AYA-CCS) experience sexual dysfunction (SD), although this healthcare need is widely underrecognized. Previous research from both AYA-CCS patients and their providers report that SD needs are unaddressed despite patient desires for SD discussions to be incorporated as part of their care. Patients and providers agree that standardized use of a patient-reported outcome measure may facilitate SD discussions; an SD screening approach was developed with patient and provider input. This study will measure the effectiveness of a standardized SD screening intervention and assess implementation outcomes and multilevel barriers and facilitators to guide future research.

Methods

This multi-site, mixed methods, type 1 effectiveness-implementation hybrid trial will be evaluated using a pre-post design (NCT05524610). The trial will enroll 86 AYA-CCS (ages 15-39) from two cancer centers in the United States. The SD intervention consists of core fundamental functions with a “menu” of intervention options to allow for flexibility in delivery and tailoring in variable contexts. Effectiveness of the intervention on facilitating SD communication will be measured through patient surveys and clinical data; multivariable logistic regression will be used for the binary outcome of self-reported SD screening, controlling for patient-level predictors. Implementation outcomes will be assessed using mixed methods (electronic health record abstraction, patient and provider surveys, and provider interviews. Quantitative and qualitative findings will be merged using a joint display to understand factors affecting intervention success.

Implications

Identification and treatment of SD in AYA-CCS is an important and challenging quality of life concern. The type 1 hybrid design will facilitate rapid translation from research to practice by testing the effects of the intervention while simultaneously identifying multilevel barriers and facilitators to real-world implementation. This approach will inform future testing and dissemination of the SD screening intervention.
Oral diadochokinesis, tongue pressure, and lip-seal strength in Japanese workers: A cross-sectional study
Authors: Minoura Akira , Ihara Yoshiaki , Kato Hirotaka , Murakami Kouzou , Watanabe Yoshio , Hirano Kojiro , Ito Yoshinori , Kokaze Akatsuki
Published: June 2024

This cross-sectional study investigated the correlation between lip-seal strength, tongue pressure, and oral diadochokinesis (OD) in Japanese workers. The relationships between lip-seal strength, tongue pressure, and OD by age groups were investigated using multiple regression analyses on 496 workers. OD was measured using the number of consecutive “Pa,” “Ta,” and “Ka” vocalizations that could be produced in 5 s. In this study, 478 participants (437 males and 41 females) were included in the analysis after excluding 18 participants who could not complete all oral cavity measurements. This study revealed a significant positive correlation between “Pa,” “Ta,” and “Ka,” with correlation coefficients of 0.500–0.665. Lip-seal strength only significantly correlated positively with “Pa”; however, tongue pressure significantly correlated positively with all of “Pa,” “Ta,” and “Ka” vocalizations. Regarding body mass index (BMI), no significant relationship with either “Pa,” “Ta,” or “Ka” was observed. As a result of aging, “Ta” and “Ka” showed a significant negative correlation with age. Multiple regression analyses, which included age, sex, BMI, alcohol consumption, and smoking, revealed a strong association between “Pa,” “Ta,” and “Ka” and lip-seal strength. However, only “Pa” showed a significant correlation with tongue pressure. Even in young and middle-aged adults, OD may be associated with lip-seal strength and tongue pressure. Measuring OD through dental screening of workers will help prevent the disease across a wide age range.
From Soil to Surface: Exploring the Impact of Green Infrastructure on Microbial Communities in the Built Environment
Authors: Mcgonigal Malin , Ito Kohei
Published: June 2024

High microbial diversity offers extensive benefits to both the environment and human health, contributing to ecosystem stability, nutrient cycling, and pathogen suppression. In built environments, factors such as building design, human activity, and cleaning protocols influence microbial communities. This study investigates the impact of landscape design on microbial diversity and function within the "Visionary Lab" exhibition in Tokyo, Japan, using 16S rRNA gene amplicon sequencing and shallow shotgun sequencing. Despite the limited sample size, the study suggests that the Visionary Lab samples may exhibit higher microbial diversity compared to other museum areas. Potential distinct microbial community structures may be correlated with sampling locations. However, despite this, no consistent patterns were observed in virulence factors or antimicrobial resistance genes across the samples. Metabolic function analysis showed varied profiles, suggesting diverse ecological interactions influenced that may be by the curated landscape. This suggest that the curated landscape design may have the potential to enhance microbial diversity, highlighting a possible avenue to create healthier and more sustainable built environments. However, the lack of consistent patterns in virulence factors and antimicrobial resistance genes underscores the complexity of microbial community dynamics.
Rapid evolution of fine-scale recombination during domestication
Authors: Liu Zheng-Xi , Li Ming , Si Si , Chen Jian-Hai , Hu Li-Rong , Peng Min-Sheng , Yin Ting-Ting , Esmailizadeh Ali , Zhang Chang , Qu Lu-Jiang , Lu Xue-Mei , Han Jian-Lin , Zhang Ya-Ping , Wang Ming-Shan
Published: June 2024

Recombination serves as a central force driving the evolution of genomic diversity in sexually reproducing organisms. Despite its fundamental role, the evolutionary dynamics of recombination rates remain largely elusive. The domestication of animals, characterized by dynamic selective pressures, provides a unique lens through which to investigate these phenomena. Here, we constructed a fine-scale recombination map using whole-genome data from domestic chickens, including both contemporary commercial breeds and their wild progenitor, the Red Junglefowl (RJF). Our analysis reveals a rapid evolution of the recombination landscape within and between chicken populations, and we find that the average recombination rate decreased during chicken domestication. Remarkably, this trend is further corroborated by re-analysis of the genomes of several domestic species including ducks, goats, pigs, and sheep. Contrary to the hypothesis that domestication leads to an increase in recombination rates, our results provide no support for such a scenario. We suggest that a low recombination rate is beneficial for maintaining uniform and stable phenotypes in domestic breeds during selective inbreeding. Furthermore, we find significant variation in recombination hotspots across chicken populations, which is particularly pronounced in commercial breeds despite their recent divergence. The rapid turnover of recombination hotspots and coldspots appears to be closely linked to selective sweeps. Interestingly, in contrast to prevailing observations in most species, we find that long-term selective inbreeding results in a negative correlation between recombination rates and the frequency of introgressed ancestry from other RJF subspecies. Our results provide insights into the complex interplay of evolutionary forces shaping the evolution of recombination.
c-di-GMP modulates ribosome assembly by inhibiting rRNA methylation
Authors: Yu Siqi , Hu Zheyao , Xu Xiaoting , Liang Xiaoran , Shen Jiayi , Liu Min , Lin Mingxi , Chen Hong , Marti Jordi , Tao Sheng-ce , Xu Zhaowei
Published: June 2024

Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial secondary messenger, with diverse functions, many of which are yet to be uncovered. Stemming from anEscherichia coliproteome microarray, we found that c-di-GMP bound to 23S rRNA methyltransferases (RlmI and RlmE). rRNA methylation assays showed that c-di-GMP inhibits RlmI activity, thereby modulating ribosome assembly. Based on molecular dynamic simulation and mutagenesis studies, we found that c-di-GMP binds to RlmI at residues R64, R103, G114, and K201. Structural simulation revealed that c-di-GMP quenches RlmI activity by inducing the closure of the catalytic pocket. Furthermore, we revealed that c-di-GMP promotes antibiotic tolerance by regulating RlmI activity, which played a role in antibiotic-resistant strains. Finally, the binding and methylation assays showed that the effect of c-di-GMP on RlmI is conserved, at least in various pathogenic bacteria. This study discovered an unexpected functional role of c-di-GMP in regulating ribosome assembly by inhibiting rRNA methylases. This study identified an unexpected but crucial member among the c-di-GMP effectors.

Highlights

c-di-GMP regulates ribosome assembly inEscherichia coli.

c-di-GMP inhibits rRNA methylation activity of RlmI by inducing catalytic pocket closure.

c-di-GMP promotes antibiotic resistance by regulating ribosome assembly.

Graphical Abstract
Poly-unsaturated Fatty Acids fromThamnidium elegansandMortierella alpinaSuppress Prostate Cancer Cells Proliferation and Migration
Authors: Kalampounias Georgios , Dritsas Panagiotis , Karayannis Dimitris , Androutsopoulou Theodosia , Gardeli Chrysavgi , Papanikolaou Seraphim , Aggelis George , Katsoris Panagiotis
Published: June 2024

Thamnidium elegansandMortierella alpinaare two oleaginous fungi that belong to Mucoromycota that synthesize polyunsaturated fatty acids which are credited with multiple health benefits and possible anticancer properties. These fungi were cultivated on culture media with glucose or glycerol as a carbon source. After extracting the lipids, we transformed them into fatty acid lithium salts (FALS), which are water-soluble and absorbable mammalian cells, including DU-145 and PC-3 cancer cells. The two cell lines, both long-established prostate cancer models, were treated with FALS and indicated increased susceptibility to the lipid derivatives. The viability and proliferation rates were significantly reduced, as well as their migratory capabilities, which were significantly impaired compared to olive-oil-derived FALS, which were used as a control substance. We conclude that the FALS derivatives of microbial lipids from these organisms exhibit anticancer effects by suppressing the proliferation and migration of human prostate cancer cell lines.
Immigrant birds learn from socially observed differences in payoffs when their environment changes
Authors: Chimento Michael , Alarcón-Nieto Gustavo , Aplin Lucy M.
Published: June 2024

Longstanding theory predicts that strategic flexibility in when and how to use social information can help individuals make adaptive decisions, especially when environments are temporally or spatially variable. A short-term increase in reliance on social information under these conditions has been experimentally shown in primates, including humans, but whether this occurs in other taxa is unknown. We asked whether migration between spatially variable environments affected social information use with a large-scale cultural diffusion experiment with wild great tits (Parus major) in captivity, a small passerine bird that can socially learn novel behaviors. We simulated an immigration event where knowledgeable birds were exchanged between groups with opposing preferences for a socially learned foraging puzzle, living in similar or different environments. We found evidence that both immigrants and residents were influenced by social information and attended to the rewards that others received. Our analysis supported the use of a payoff-biased social learning by immigrants when both resources and habitat features were spatially variable. In contrast, immigrants relied more-so on individual learning when payoffs or the environment were unchanged. In summary, our results suggest that great tits assess the payoffs others receive, and are more influenced by socially observed differences in payoffs when environmental cues differ in their new environment. Our results provide experimental support for the hypothesis that spatial variability is a strong driver for the evolution of social learning strategies.
Phage genome architecture and GC content: Structural genes and where to find them
Authors: Das Ritam , Rahlff Janina
Published: June 2024

Bacteriophages, the ubiquitous bacterial viruses, are the most abundant biological entities on Earth. However, information regarding the impact of environmental factors on the genetic makeup of phages is scarce. Based on the analysis of genomes of 45 phage isolates from different ecosystems we demonstrate a significant (p< 0.0001) positive correlation of the number of structural genes and their placement in above-average guanine-cytosine (GC) content of the genome. This feature appears to be more evident in isolates from deep-sea and sea-ice environments compared to desert and Baltic Sea slick, indicating a potential ecosystem-based factor (although insignificant due to low sample size). Additionally, the percentage of structural genes in above-average GC regions was found to be significantly (p= 0.0038) negatively correlated with the genome size of the phages and significantly (p= 0.0266) positively correlated with the overall GC for phage genomes > 50 kb, but not for genomes < 50 kb (p =0.556). We therefore propose a relationship of structural genes and GC content, a property that may influence the adaptation and evolution of phages in various environmental niches.
Genetic selection for residual feed intake impacts the functional redundancy of the gut microbiota in pigs during the growing-finishing period
Authors: Zemb Olivier , achard caroline S , ESTELLE Jordi , cauquil laurent , denis catherine , billon yvon , combes sylvie , rogel-gaillard claire , gilbert helene
Published: June 2024

Background: Improving feed efficiency is an unvarying goal in livestock production. The role of gut microbial communities in feed efficiency was investigated in two divergent pig lines selected for their residual feed intake (RFI), which is the difference between the observed feed consumption of an animal and that predicted for its maintenance and production requirements. Hence, RFI is a measure of net feed efficiency. Results: By sequencing the 16S rRNA genes from fecal samples, we found that the microbiota of low RFI pigs (LRFI; n=12) was significantly depleted in four operational taxonomic units (OTUs) belonging to Prevotella, Feacalibacterium and Lactobacillus genera by comparison to high RFI pigs (HRFI; n=11). Inferring KEGG orthologs from the 16S rRNA gene sequencing data showed that LRFI pigs have 20% more functional redundancy than HRFI pigs. The inferred orthologs held more discriminative power than the OTU approach, which might be inherently flawed if functionally equivalent OTUs compete for the same niche. Conclusions: Gut microbiota of LRFI pigs had different microbial operational taxonomic units and a higher functional redundancy, which were more shared suggesting a role of the gut microbiota in the global feed efficiency according to Tax4Fun but this inference based on 16S data has to be verified in future work.
Phageome transfer from gut to circulation and its regulation by human immunity
Authors: Szymczak Aleksander , Gembara Katarzyna , Ferenc Stanisław , Majewska Joanna , Miernikiewicz Paulina , Harhala Marek , Rybicka Izabela , Strapagiel Dominik , Słomka Marcin , Lach Jakub , Gnus Jan , Stączek Paweł , Witkiewicz Wojciech , Dąbrowska Krystyna
Published: June 2024

Bacteriophages are a critical part of the human microbiome, especially in the gastrointestinal tract. While phage translocation beyond the gut is known, its regulation within phageomes and interaction with immune responses remain unclear. This study explores the taxonomic structure of the phageome, lymphatic filtration, and phage-specific IgG induction as factors regulating phage translocation from the gut to the bloodstream.

Mucosal intestinal biopsies and serum samples from 38 patients were analyzed to determine gut and blood phageome compositions. Phage epitopes targeted by IgGs were identified via immunoprecipitation of a phageome-wide epitope library and high-throughput sequencing. In vivo, phage arrest in lymph nodes was studied using a mouse model.

Tequatroviruses and Kayviruses were abundant in the gut mucosa and frequently translocated to blood circulation. However, gut-blood phageome correlation was moderate. Phage-specific IgGs reduced targeted phages in both blood and gut mucus, limiting translocation. Lymphatic tissues also sequestered phages in vivo.

We propose that translocation involves multiple steps, beginning with epithelial transcytosis, followed however by filtration in lymphatic tissues, which limits translocation dynamics in vivo. While the gut phageome significantly contributes to circulating phages, other sources also play a role. These findings improve our understanding of phageome functions and their medical applications.
A structure-based mechanism for initiation of AP-3 coated vesicle formation
Authors: Begley Matthew , Aragon Mahira , Baker Richard W
Published: June 2024

Adaptor protein complex 3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 is in a constitutively open, active conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question. To understand the mechanism of AP-3 membrane recruitment and activation, we reconstituted the core of human AP-3 and determined multiple structures in the soluble and membrane-bound states using electron cryo-microscopy (cryo-EM). Similar to yeast AP-3, human AP-3 is in a constitutively open conformation, with the cargo-binding domain of the μ3 subunit conformationally free. To reconstitute AP-3 activation by the small GTPase Arf1, we used lipid nanodiscs to build Arf1-AP-3 complexes on membranes and determined three structures that show the stepwise conformational changes required for formation of AP-3 coated vesicles. First, membrane-recruitment is driven by one of two predicted Arf1 binding sites on AP-3. In this conformation, AP-3 is flexibly tethered to the membrane and its cargo binding domain remains conformationally dynamic. Second, cargo binding causes AP-3 to adopt a fixed position and rigidifies the complex, which stabilizes binding for a second Arf1 molecule. Finally, binding of the second Arf1 molecule provides the template for AP-3 dimerization, providing a glimpse into the first step of coat polymerization. We propose coat polymerization only occurs after cargo engagement, thereby linking cargo sorting with assembly of higher order coat structures. Additionally, we provide evidence for two amphipathic helices in AP-3, suggesting that AP-3 contributes to membrane deformation during coat assembly. In total, these data provide evidence for the first stages of AP-3 mediated vesicle coat assembly.
New metric improving Bayesian calibration of a multistage approach studying hadron and inclusive jet suppression
Authors: Fan W. , Vujanovic G. , Bass S. A. , Angerami A. , Arora R. , Cao S. , Chen Y. , Dai T. , Du L. , Ehlers R. , Elfner H. , Fries R. J. , Gale C. , He Y. , Heffernan M. , Heinz U. , Jacak B. V. , Jacobs P. M. , Jeon S. , Ji Y. , Kasper L. , Kordell M. , Kumar A. , Latessa J. , Lee Y.-J. , Lemmon R. , Liyanage D. , Lopez A. , Luzum M. , Majumder A. , Mak S. , Mankolli A. , Martin C. , Mehryar H. , Mengel T. , Mulligan J. , Nattrass C. , Norman J. , Paquet J.-F. , Parker C. , Putschke J. H. , Roland G. , Schenke B. , Schwiebert L. , Sengupta A. , Shen C. , Sirimanna C. , Soeder D. , Soltz R. A. , Soudi I. , Strickland M. , Tachibana Y. , Velkovska J. , Wang X.-N. , Zhao W. ,   JETSCAPE Collaboration
Published: June 2024

We study parton energy-momentum exchange with the quark gluon plasma (QGP) within a multistage approach composed of in-medium Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution at high virtuality, and (linearized) Boltzmann transport formalism at lower virtuality. This multistage simulation is then calibrated in comparison with high-pT charged hadrons, D mesons, and the inclusive jet nuclear modification factors, using Bayesian model-to-data comparison, to extract the virtuality-dependent transverse momentum broadening transport coefficient q̂. To facilitate this undertaking, we develop a quantitative metric for validating the Bayesian workflow, which is used to analyze the sensitivity of various model parameters to individual observables. The usefulness of this new metric in improving Bayesian model emulation is shown to be highly beneficial for future such analyses.

Published by the American Physical Society
2024
High-energy neutrino deep inelastic scattering cross sections
Authors: Xie Keping , Gao Jun , Hobbs T. J. , Stump Daniel R. , Yuan C.-P. ,   CTEQ-TEA Collaboration
Published: June 2024

We present a state-of-the-art prediction for cross sections of neutrino deep inelastic scattering (DIS) from nucleon at high neutrino energies, Eν, up to 1000 EeV (1012  GeV). Our calculations are based on the latest CT18 NNLO parton distribution functions (PDFs) and their associated uncertainties. To make predictions for the highest energies, we extrapolate the PDFs to small x according to several procedures and assumptions, thus affecting the uncertainties at ultrahigh Eν; we quantify the uncertainties corresponding to these choices. Similarly, we quantify the uncertainties introduced by the nuclear corrections that are required to evaluate neutrino-nuclear cross sections for the neutrino observatories. These results can be applied to currently running astrophysical neutrino observatories, such as IceCube and KM3NeT, as well as various future experiments that have been proposed.

Published by the American Physical Society
2024
Higher-order NLO initial state QED radiative corrections to
e+e−
annihilation revisited
Authors: Arbuzov A. B. , Voznaya U. E.
Published: June 2024

Radiative corrections due to initial state radiation in electron-positron annihilation are calculated within the QED structure function approach. Results are shown in the next-to-leading logarithmic approximation up to O(α4L3) order, where L=ln(s/me2) is the large logarithm. Several mistakes in previous calculations are corrected. The results are relevant for future high-precision experiments at e+e− colliders.

Published by the American Physical Society
2024
Z3
lattice gauge theory as a toy model for dense QCD
Authors: Hidaka Yoshimasa , Tanizaki Yuya , Yamamoto Arata
Published: June 2024

We propose the (3+1)-dimensional Z3 lattice gauge theory coupled with the 2-flavor Wilson-Dirac fermion as a toy model for studying quantum chromodynamics (QCD) at nonzero density. We study its phase diagram in the space of the lattice gauge couplings g2 and the quark chemical potentials μ and discuss the similarity and difference compared with anticipated behaviors of actual QCD. This model also provides a testing ground for various algorithms of the numerical Hamiltonian formalism as its Hilbert space is finite-dimensional in a finite box.

Published by the American Physical Society
2024