bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utility of whole-genome sequencing to identify likely transmission pairs for pathogens with slow and variable evolution
Authors: Wood A. J. , Benton C. H. , Delahay R. J. , Marion G. , Palkopoulou E. , Pooley C. M. , Smith G. C. , Kao R. R. 
Published: May 2024

AbstractPathogen whole-genome sequencing (WGS) has been used to track the transmission of infectious diseases in extraordinary detail, especially for pathogens that undergo fast and steady evolution, as is the case with many RNA viruses. However, for other pathogens evolution is less predictable, making interpretation of these data to inform our understanding of their epidemiology more challenging and the value of densely collected pathogen genome data uncertain. Here, we assess the utility of WGS for one such pathogen, in the “who-infected-whom” identification problem. We study samples from hosts (130 cattle, 111 badgers) with confirmed infection ofM. bovis(causing bovine Tuberculosis), which has an estimated clock rate as slow as ∼0.1–1 variations per year. For each potential pathway between hosts, we calculate the relative likelihood that such a transmission event occurred. This is informed by an epidemiological model of transmission, and host life history data. By including WGS data, we shrink the number of plausible pathways significantly, relative to those deemed likely on the basis of life history data alone. Despite our uncertainty relating to the evolution ofM. bovis, the WGS data are therefore a valuable adjunct to epidemiological investigations, especially for wildlife species whose life history data are sparse.
Evidence for a push-pull interaction between superior colliculi in monocular dynamic vision mode
Authors: Gil Rita , Valente Mafalda , Fernandes Francisca F. , Shemesh Noam 
Published: May 2024

AbstractVisual perception can operate in two distinct vision modes - static and dynamic - that have been associated with different neural activity regimes in the superior colliculus (SC). The static vision mode (low flashing frequencies) is associated with strong SC activation modulated by cortical gain and inhibitory intertectal effects, while the dynamic vision mode (high flashing frequencies) evokes the continuity illusion, with associated suppression of SC neural activity. However, the pathway-wide mechanisms underpinning the dynamic vision mode remain poorly understood, especially in terms of corticotectal and tectotectal feedback. Here, we harness rat functional MRI combined with brain lesions to investigate whole-pathway interactions in the dynamic vision mode. In the SC, we find contralateral suppression of activity opposing positive ipsilateral neural activation upon monocular visual stimulation in the dynamic vision mode. A cortical amplification effect was confirmed for both static and dynamic vision modes through cortical lesions, while further lesioning ipsilateral SC led to a boost in the contralateral negative signals, suggesting an active push-pull interaction between ipsilateral and contralateral SCs during the dynamic vision mode regime. This push-pull interaction is specific to the dynamic vision mode; in the static vision mode, both SCs show similar response polarities. These results highlight hitherto unreported frequency-dependent modulations in the tectotectal pathway and further challenge the contemporary notion that intertectal connections solely serve as reciprocal inhibitory mechanisms for avoiding visual blur during saccade occurrence.One Sentence SummaryOpposing signals between superior colliculi in the dynamic vision mode suggest an active push-pull interaction within the tectotectal commissural pathway.
An efficient biochemical method for characterizing and classifying potentially amyloidogenic and therapeutic peptides
Authors: Pradeau-Phélut Lucas , Alvès Stacy , Le Tareau Léo , Larralde Cyann , Bernard Emma , Kee Him Josephine Lai , Lepvrier Eléonore , Bron Patrick , Delamarche Christian , Garnier Cyrille 
Published: May 2024

AbstractAmyloidosis are proteinopathies characterized by systemic or organ-specific deposition of proteins in the form of amyloid fibers. Nearly forty proteins have been identified to play a role in these pathologies and the structures of the associated fibers are beginning to be determined by Cryo-EM. However, the molecular events underlying the process, such as fiber nucleation and elongation, are poorly understood, which impairs developing efficient therapies. In most cases, only a few dozen amino acids of the pathological protein are found in the final structure of the fibers, while amyloid peptides comprising 5 to 10 amino acids are involved in fibers nucleation process. The identification and biochemical characterization of these peptides is therefore of major scientific and clinical importance.In silicoapproaches are limited due to the peptides’ small size and long-distance intra- and intermolecular interactions that occur during nucleation. To address this problem, we developed a novel biochemical method for characterizing and classifying batches of related peptides. Initial work to optimize our approach is based on the reference peptide PHF6 (ß1) from Microtubule Associated Protein Tau (MAPT) as compared to 22 related peptides. We classified these peptides into groups displaying different biochemical properties, and thereby identified new amyloid peptides and peptides with therapeutic potential. We underline that our method is applicable to any family of peptides and could be scaled up for high-throughput analyses.
Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes
Authors: Knappeová Barbora , Mlýnský Vojtěch , Pykal Martin , Šponer Jiří , Banáš Pavel , Otyepka Michal , Krepl Miroslav 
Published: May 2024

AbstractMixed double helices formed by RNA and DNA strands, commonly referred to as hybrid duplexes or hybrids, are essential in biological processes like transcription and reverse transcription. They are also important for their applications in CRISPR gene editing and nanotechnology. Yet, despite their significance, the hybrids have been seldom modeled by atomistic molecular dynamics methodology, and there is no benchmark study systematically assessing the force-field performance. Here, we present an extensive benchmark study of the hybrids using contemporary and commonly utilized pairwise additive and polarizable nucleic acid force fields. Our findings indicate that none of the available force-field choices accurately reproduces all the characteristic structural details of the hybrids. The AMBER force fields are unable to populate the C3′-endo (north) pucker of the DNA strand and underestimate inclination. CHARMM force field accurately describes the C3′-endo pucker and inclination but shows base pair instability. The polarizable force fields struggle with accurately reproducing the helical parameters. Some force-field combinations even demonstrate a discernible conflict between the RNA and DNA parameters. In this work, we offer a candid assessment of the force-field performance for mixed DNA/RNA duplexes. We provide guidance on selecting utilizable force-field combinations, as well as highlight potential pitfalls and best practices for obtaining optimal performance.
Species interactions and food-web context drive temperature-dependent prey evolution
Authors: Han Ze-Yi , Yuan Yaning , DeWitt Katrina , Yammine Andrea , Wieczynski Daniel J. , Onishi Masayuki , Gibert Jean P. 
Published: May 2024

ABSTRACTUnderstanding how global warming shapes species evolution within communities is a pressing goal of ecology. Temperature affects interacting species and can lead to changes in species interactions, but how that will alter species evolutionary trajectories within complex food webs is poorly understood. Here we address 1) whether different predators affect prey evolution differentially, 2) whether the food web context in which this happens influences prey evolution, 3) whether temperature affects prey evolution directly, and 4) whether ecological interactions mediate how temperature affects prey evolution. We use a combination of mathematical modeling and experimental evolution assays in microbial food webs composed of prey algae and their protists predators. We found that temperature alone doesn’t drive prey evolution unless predators are involved. Importantly, the influence of temperature through predation is contingent on the food web structure. This leads to distinct evolutionary trajectories when prey evolves with predators alone or with a competing predator present. Our findings indicate that the species evolution to warming is likely contingent on their specific ecological contexts, suggesting that similar species across different food webs could exhibit diverse evolutionary responses to new climates.
GPT-4 based AI agents – the new expert system for detection of antimicrobial resistance mechanisms?
Authors: Giske Christian G. , Bressan Michelle , Fiechter Farah , Hinic Vladimira , Mancini Stefano , Nolte Oliver , Egli Adrian 
Published: May 2024

AbstractBackgroundEUCAST recommends a two-step process for beta-lactamases in Gram-negative bacteria. Screening with minimal inhibitory concentrations (MICs) or inhibition zone diameters for potential extended spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase, or carbapenemase production is followed by confirmatory tests. GPT-4 and its newly released customized GPT-agent may support the initial EUCAST-screening process. We aimed to validate a customized GPT-agent to identify potential resistance mechanisms.MethodsWe used 225 Gram-negative isolates. Based on phenotypic resistances against beta-lactam antibiotics, we formed four categories: “none”, “ESBL”, “AmpC”, or “carbapenemase”. We included 862 phenotypic categories. Next, we customized a GPT-agent with EUCAST-guidelines, expert rules, and EUCAST-breakpoint table (v13.1). We compared routine diagnostic outputs (reference) to (i) EUCAST-GPT-expert, (ii) medical microbiologists, and (iii) GPT-4 without customization. We determined performance as sensitivities and specificities to flag suspect resistance mechanisms.ResultsThree human readers showed concordance in 814/862 (94.4%) phenotypic categories and used in median eight words (IQR 4-11) for reasoning. Median sensitivity and specificity for ESBL, AmpC, and carbapenemase were 98%/99.1%, 96.8%/97.1%, and 95.5%/98.5%, respectively. Three independent prompting rounds of the GPT-agent showed concordance in 706/862 (81.9%) categories but used in median 158 words (IQR 140-174) for reasoning,. Median sensitivity and specificity for ESBL, AmpC, and carbapenemase prediction were 95.4%/69.23%, 96.9%/86.3%, and 100%/98.8%, respectively. In the non-customized GPT-4, 169/862 (19.6%) categories could be interpreted. Of these 137/169 (81.1%) categories agreed with routine diagnostic. The non-customized GPT-4 used in median 85 words (IQR 72-105) for reasoning.ConclusionHuman experts showed higher concordance and shorter argumentations compared to GPT-agents. Human experts showed comparable median sensitivities and higher specificities compared to GPT-agents. GPT-agents showed more unspecific flagging of ESBL and AmpC, potentially, resulting in additional testing, diagnostic delays, and higher costs. GPT-4 and GPT-agents are not IVDR/FDA-approved, but validation of LLMs is critical and datasets for benchmarking are needed.
The distribution of regions of homozygosity (ROH) among consanguineous populations - implications for a routine genetic counseling service
Authors: Gafni-Amsalem Chen , Warwar Nasim , Khayat Morad , Tatour Yasmin , Abuleil-Zuabi Olfat , Campisi-Pinto Salvatore , Carmi Shai , Shalev Stavit A. 
Published: May 2024

AbstractBackgroundRegions of homozygosity (ROH) increase the risk of recessive disorders, and guidelines recommend reporting of excessive ROH in prenatal testing. However, ROH are common in populations that practice endogamy or consanguinity, and cutoffs for reporting ROH in such populations may not be evidence-based.MethodsWe reviewed prenatal testing results (based on cytogenetic microarrays) from 2191 pregnancies in the Jewish and non-Jewish populations of Northern Israel and estimated the prevalence of ROH according to self-reported ethnicity and parental relationships.ResultsThe proportion of the genome in ROH, ROH rate, was higher in non-Jews [Mean(SD)=2.91%(3.92%); max=25.54%; N=689] than in Jews [Mean(SD)=0.81%(0.49%); max=3.93%; N=1502]. In the non-Jewsih populations, consanguineous marriages had the highest ROH rates [Mean(SD)=7.14%(4.55%), N=217], followed by endogamous [Mean(SD)=1.13%(1.09%), N=283]) and non-endogamous [Mean(SD)=0.69%(0. 56%), N=189]) marriages. ROH rates were greater than 5%, the ACMG-recommended cutoff, in 149/689 (21.63%) of the non-Jewish samples. Within the Jewish populations, the rates were similar between Ashkenazi, North African, and Middle Eastern Jews, but were higher for six consanguineous unions [Mean(SD)=2.38%(1.23%)] and when spouses belonged to the same sub-population.ConclusionsGiven the high ROH rates we observed in some subjects, we suggest that assessing the risk for recessive conditions in consanguineous/endogamous populations should be done before the first pregnancy, through genetic counseling and sequencing. Such an approach will: (1) identify couples who are at risk and counsel them on reproductive options; and (2) avoid the stress that couples who are not at risk may experience due to a prenatal ROH report.
Early adulthood socioeconomic trajectories contribute to inequalities in adult diet quality, independent of childhood and adulthood socioeconomic position
Authors: Tao Yinhua , Maddock Jane , Howe Laura D , Winpenny Eleanor M 
Published: May 2024

AbstractBackgroundDiet is an important risk factor for cardiovascular disease and shows well-established socioeconomic patterning among adults. However, less clear is how socioeconomic inequalities in diet develop across the life course. This study assessed the associations of early adulthood socioeconomic trajectories (SETs) with adult diet quality, adjusting for childhood socioeconomic position (SEP) and testing for mediation by adulthood SEP.MethodsParticipants from the 1970 British Cohort Study with socioeconomic data in early adulthood were included (n=12434). Diet quality at age 46 years, evaluated using the Mediterranean diet pyramid, was regressed on six previously identified classes of early adulthood SETs between ages 16 and 24 years, including a Continued Education class, four occupation-defined classes, and an Economically Inactive class. Causal mediation analyses tested the mediation of the association via household income and neighbourhood deprivation at age 46 years separately. Models were adjusted for sex, childhood SEP, adolescent diet quality and adolescent health.ResultsThe Continued Education class showed the best diet quality at age 46 years, while little difference in diet quality was found among the remaining SET classes. The association between the Continued Education class and adult diet quality was independent of parental SEP in childhood, and was largely not mediated by household income or neighbourhood deprivation (0.7% and 3.7% of the total effect mediated, respectively) in mid-adulthood.ConclusionsEarly adulthood SETs independently contribute to adult diet quality, with continuing education associated with better adherence to Mediterranean diet. Early adulthood therefore represents a critical period for intervention to alleviate dietary inequalities in later life.Key MessagesLife course epidemiology research aims to identify potential windows of change in life to prevent the establishment of socioeconomic inequalities in diet and diet-related cardiovascular health.Early adulthood socioeconomic trajectories contributed to adult diet quality independent of childhood and adulthood socioeconomic position, with continuing education between ages 16 and 24 years associated with better diet quality at age 46 years.Early adulthood represents a critical period for intervention to alleviate socioeconomic inequalities in diet persisting into adulthood.
Novel phages ofPseudomonas syringaeunveil numerous potential auxiliary metabolic genes
Authors: Feltin Chloé , Garneau Julian R. , Morris Cindy E. , Bérard Annette , Torres-Barceló Clara 
Published: May 2024

AbstractRelatively few phages that infect plant pathogens have been isolated and investigated. ThePseudomonas syringaespecies complex is present in various environments, including plants. It can cause major crop diseases, such as bacterial canker on apricot trees. This study presents a collection of 25 unique phages genomes that infectP. syringae. These phages were isolated from apricot orchards with bacterial canker symptoms after enrichment with 21 strains ofP. syringae. This collection comprises mostly virulent phages, with only three being temperate. They belong to 14 genera, 11 of which are newly discovered, and 18 new species, revealing great genetic diversity within this collection. Novel DNA packaging systems have been identified bioinformatically in one of the new phage species, but experimental confirmation is required to define the precise mechanism. Additionally, many phage genomes contain numerous potential auxiliary metabolic genes with diversified putative functions. At least three phages encode genes involved in bacterial tellurite resistance, a toxic metalloid. This suggests that viruses could play a role in bacterial stress tolerance. This research emphasises the significance of continuing the search for new phages in the agricultural ecosystem to unravel novel ecological diversity and new gene functions. This work contributes to the foundation for future fundamental and applied research on phages infecting phytopathogenic bacteria.
Inducing aggresome and stable tau aggregation in Neuro2a cells with an optogenetic tool
Authors: Sakuragi Shigeo , Uchida Tomoya , Kato Naoki , Zhao Boxiao , Takahashi Toshiki , Hattori Akito , Sakata Yoshihiro , Soeda Yoshiyuki , Takashima Akihiko , Yoshimura Hideaki , Matsumoto Gen , Bannai Hiroko 
Published: May 2024

Tauopathy is a spectrum of diseases characterized by fibrillary tau aggregate formation in neurons and glial cells in the brain. Tau aggregation originates in the brainstem and entorhinal cortex and then spreads throughout the brain in Alzheimer’s disease (AD), which is the most prevalent type of tauopathy. Understanding the mechanism by which locally developed tau pathology propagates throughout the brain is crucial for comprehending AD pathogenesis. Therefore, a novel model of tau pathology that artificially induces tau aggregation in targeted cells at specific times is essential. This study describes a novel optogenetic module, OptoTau, which is a human tau with the P301L mutation fused with a photosensitive protein CRY2olig, inducing various forms of tau according to the temporal pattern of blue light illumination pattern. Continuous blue light illumination for 12 h to Neuro2a cells that stably express OptoTau (OptoTauKI cells) formed clusters along microtubules, many of which eventually accumulated in aggresomes.Conversely, methanol-resistant tau aggregation was formed when alternating light exposure and darkness in 30-min cycles for 8 sets per day were repeated over 8 days. Methanol-resistant tau was induced more rapidly by repeating 5-min illumination followed by 25-min darkness over 24 h. These results indicate that OptoTau induced various tau aggregation stages based on the temporal pattern of blue light exposure. Thus, this technique exhibits potential as a novel approach to developing specific tau aggregation in targeted cells at desired time points.SignificanceThis study developed an approach to manipulate tau aggregation in a blue light-dependent manner using cells that stably express OptoTau, which is an optogenetic tool based on the CRY2olig module. Tau accumulation in aggresomes or stable tau aggregation were selectively induced by blue light illumination conditions. These results are crucial as they provide a new technological basis for establishing a singular point of tau aggregation in specific targeted cells at a particular time.
A phylogenetic host range index reveals contrasted relationships between phage virulence and specialisation
Authors: Torres-Barceló Clara , Boyer Claudine , Garneau Julian R. , Poussier Stéphane , Robène Isabelle , Moury Benoit 
Published: May 2024

ABSTRACTPhages are typically known for having a limited host range, targeting various strains within a specific bacterial species. However, factors like the phylogeny or epidemiology of host bacteria are often disregarded, despite their potential influence on phage specialization and virulence. This research utilizes a new “phylogenetic host range index” that accounts for the genetic diversity of bacterial hosts, to classify phages into specialists and generalists accurately. We provide evidence that the CRISPR-Cas immune system of bacteria more frequently targets generalist phages than specialist phages. We explore the hypothesis that generalist phages might exhibit lower virulence than specialist ones due to potential evolutionary trade-offs between host range breadth and virulence. Importantly, contrasted correlations between phage virulence and host range depend on the epidemiological context. A trade-off was confirmed in a homogeneous bacterial epidemiology situation, but not in more complex epidemiological scenario, where no apparent costs were detected for phages adapted to a wide range of hosts. This study highlights the need for genetic analyses in phage host range and of investigating ecological trade-offs that could improve their applications in biocontrol or therapy.
Convergent evolution associated with the loss of developmental diapause may promote extended lifespan in bees
Authors: Santos Priscila K. F. , Kapheim Karen M. 
Published: May 2024

AbstractDiapause has long been proposed to play a significant role in the evolution of eusociality in Hymenoptera. Recent studies have shown that shifts in the diapause stage precede social evolution in wasps and bees, however, the genomic basis remains unknown. Given the overlap in molecular pathways that regulate diapause and lifespan, we hypothesized that the evolutionary loss of developmental diapause may lead to extended lifespan among adults, which is a prerequisite for the evolution of eusociality. To test this, we compared 27 bee genomes with or without prepupal diapause. Our results point to several potential mechanisms for lifespan extension in species lacking prepupal diapause, including the loss of the growth hormone PTTH and its receptor TORSO, along with convergent selection in genes known to regulates lifespan in animals. Specifically, we observed purifying selection of pro-longevity genes and relaxed selection of anti-longevity genes within the IIS/TOR pathway in species that have lost prepupal diapause. Changes in selection pressures on this pathway may lead to the evolution of new phenotypes, such as lifespan extension and altered responses to nutritional signals, that are crucial for social evolution.SignificanceDiapause has long been proposed to play a significant role in the evolution of eusociality in Hymenoptera. Recent studies have shown that the loss of diapause during the prepupal stage precedes social evolution in wasps and bees. However, the genomic mechanisms underlying this phenomenon remain unknown. Through comparative genomics, we showed that the convergent loss of prepupal diapause is associated with mechanisms that may promote lifespan extension, a prerequisite for social evolution. These mechanisms include genes losses and signals of selection on genes related to aging.