bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting “pain genes”: multi-modal data integration using probabilistic classifiers and interaction networks
Authors: Zhao Na , Bennett David L , Baskozos Georgios , Barry Allison M 
Published: May 2024

AbstractAccurate identification of pain-related genes remains challenging due to the complex nature of pain pathophysiology and the subjective nature of pain reporting in humans, or inferring pain states in animals on the basis of behaviour. Here, we use a machine learning approach to identify possible “pain genes”. Labelling was based on a gold-standard list of genes with validated involvement across pain conditions, and was trained on a selection of -omics (eg. transcriptomics, proteomics, etc.), protein-protein interaction (PPI) network features, and biological function readouts for each gene. Multiple classifiers were trained, and the top-performing model was selected to predict a “pain score” per gene. The top ranked genes were then validated against pain-related human SNPs to validate against human genetics studies. Functional analysis revealed JAK2/STAT3 signal, ErbB, and Rap1 signalling pathways as promising targets for further exploration, while network topological features contribute significantly to the identification of “pain” genes. As such, a PPI network based on top-ranked genes was constructed to reveal previously uncharacterised pain-related genes including CHRFAM7A and UNC79. These analyses can be further explored using the linked open-source database athttps://livedataoxford.shinyapps.io/drg-directory/, which is accompanied by a freely accessible code template and user guide for wider adoption across disciplines. Together, the novel insights into pain pathogenesis can indicate promising directions for future experimental research.
Purified fibers in chemically defined synthetic diets destabilize the gut microbiome of an omnivorous insect model
Authors: Dockman Rachel L. , Ottesen Elizabeth A. 
Published: May 2024

1AbstractThe macronutrient composition of a host’s diet shapes its gut microbial community, with dietary fiber in particular escaping host digestion to serve as a potent carbon source for gut microbiota. Despite widespread recognition of fiber’s importance to microbiome health, nutritional research often fails to differentiate hyper-processed fibers from cell-matrix derived intrinsic fibers, limiting our understanding of how individual polysaccharides influence the gut community. We use the American cockroach (Periplaneta americana) as a model system to dissect the response of complex gut microbial communities to diet modifications that are impossible to test in traditional host models. Here, we designed synthetic diets from lab-grade, purified ingredients to identify how the cockroach microbiome responds to six different carbohydrates (chitin, methylcellulose, microcrystalline cellulose, pectin, starch, xylan) in otherwise balanced diets. We show via 16S rRNA gene profiling that these synthetic diets reduce bacterial diversity and alter the phylogenetic composition of cockroach gut microbiota in a fiber-dependent manner, regardless of the vitamin and protein content of the diet. Comparisons with cockroaches fed whole-food diets reveal that synthetic diets induce blooms in common cockroach-associated taxa and subsequently fragment previously stable microbial correlation networks. Our research leverages an unconventional microbiome model system and customizable lab-grade artificial diets to shed light on how purified polysaccharides, as opposed to nutritionally complex intrinsic fibers, exert substantial influence over a normally stable gut community.
Exploring Probiotic Potential: A Comparative Genomics and In Silico Assessment of Genes within the GenusGeobacillus
Authors: Najar Ishfaq Nabi , Sharma Prayatna , Das Rohit , Mondal Krishnendu , Singh Ashish Kumar , Radha Anu , Sharma Varsha , Sharma Sonali , Thakur Nagendra , Gandhi Sumit G. , Kumar Vinod 
Published: May 2024

AbstractThe pursuit of new probiotic targets has seen a surge, aided by next-generation sequencing, facilitating a thorough exploration of bacterial traits. The genusGeobacillusstands out as a promising target for uncovering its potential as a probiotic. The study explored the genetic attributes of the genusGeobacillusfor their resilience to gastrointestinal conditions, nutrient production, and immunomodulatory compound creation, revealing potential probiotic traits. Additionally, the research undertook predictive analyses of genomic elements such as prophages, CRISPR-Cas systems, insertion sequences, genomic islands, antibiotic resistance genes, and CAZymes. These evaluations aimed to assess the safety aspects associated with the genusGeobacillus. A comparative genomic analysis was also carried out using 18 validly published genomes of the genusGeobacillusand a few other genomes ofLactobacillusandBifidobacteriumwere taken as control. Genes associated with probiotic traits like adhesion, stress tolerance (acid/bile, osmotic, oxidative), immune modulation, and molecular chaperones were uniformly detected in theGeobacillusgenus. Notably, mobile genetic elements such as plasmids, prophages, and insertion sequences were absent, as were virulence factors, toxins, and Antibiotic resistance genes. Additionally, CRISPR-Cas systems and CAZymes were present. The pan-genome encompassed 25,284 protein-coding genes with translation. Comparative genomic analysis revealed an open pan-genome forGeobacillus. Pan-genome exhibited variability, particularly in genes linked to environmental interaction and secondary metabolite synthesis. In conclusion,Geobacillusappears potentially safe and well-suited for the gut habitat. However, furtherin vitrostudies are essential to add to the knowledge of the probiotic potential ofGeobacillusspecies.ImportanceThis comprehensive study highlights the significant probiotic potential and genetic makeup of theGeobacillusgenus, shedding light on its unique attributes in adapting to extreme environmental conditions. Understanding the probiotic properties ofGeobacillusis crucial amidst growing concerns over antibiotic resistance, offering promising alternatives for combating pathogenic microbes. Additionally, exploring the genetic diversity and adaptive mechanisms ofGeobacillusthrough genomic and metagenomic approaches provides valuable insights into its biotechnological applications and evolutionary history. By employing in-silico methods and comparative analyses with established probiotic genera, this study contributes to elucidating the probiotic characteristics ofGeobacillus, paving the way for further research in harnessing its beneficial traits for various applications in health, biotechnology, and environmental remediation.
A duplexed CRISPRi-based approach to predict synergistic antibiotic targets inEscherichia coli
Authors: Xiong Xianyi , Furseth Hannah , McCoy Brady , Slavic Lauren , Yuan Xun , Chen Sydney , Baughn Anthony D. , Minato Yusuke , Harcombe William R. 
Published: May 2024

AbstractCo-repressing drug targets with CRISPR interference (CRISPRi) has the potential to predict both synergistic and additive drug combinations. In a screen experiment withEscherichia coli, pairwise gene co-repression assays correctly predicted the interaction type observed for 36 antibiotic pairs in checkerboard assays. Furthermore, we used this approach to identify promising synergistic interactions with a gene currently not targeted by clinical antibiotics. CRISPRi can systematically test the impact of gene inhibitions and identify novel drug targets.
Expanding the cultivable human archaeome:Methanobrevibacter intestinisp. nov. and strainMethanobrevibacter smithii “GRAZ-2”from human feces
Authors: Weinberger Viktoria , Mohammadzadeh Rokhsareh , Blohs Marcus , Kalt Kerstin , Mahnert Alexander , Moser Sarah , Cecovini Marina , Mertelj Polona , Zurabishvili Tamara , Wolf Jacqueline , Shinde Tejus , Madl Tobias , Habisch Hansjörg , Kolb Dagmar , Pernitsch Dominique , Hingerl Kerstin , Metcalf William , Moissl-Eichinger Christine 
Published: May 2024

AbstractTwo mesophilic, hydrogenotrophic methanogens, WWM1085 andM. smithiiGRAZ-2 were isolated from human fecal samples. WWM1085 was isolated from an individual in the USA, and represents a novel species with in the genusMethanobrevibacter.M. smithiiGRAZ-2 (= DSM 116045) was retrieved from fecal samples of a European, healthy female and represents a novel strain within this genus. BothMethanobrevibacterrepresentatives form non-flagellated, short rods with variable morphologies and the capacity to form filaments. Both isolates showed the typical fluorescence of F420and methane production.Compared toM. smithiiGRAZ-2, WWM1085 did not accumulate formate when grown on H2and CO2. The optimal growth conditions were at 37°C, and pH 7. Full genome sequencing revealed a genomic difference of WWM1085 to the type strain ofM. smithiiPS (type strain; DSM 861), with 93.55% ANI and major differences in the sequence of itsmcrAgene (3.3% difference in nucleotide sequence). Differences in the 16S rRNA gene were very minor and thus distinction based on this sequence might not be possible.M. smithiiGRAZ-2 was identified as a novel strain within theMethanobrevibactergenus (ANI 99.04 % toM. smithiiPS).Due to the major differences of WWM1085 andM. smithiitype strain PS in phenotypic, genomic and metabolic features, we proposeM. intestinisp. nov. as a novel species with WWM1085 as the type strain (DSM 116060T = CECT 30992).
Genomic perspectives on foodborne illness
Authors: Lipman David J. , Cherry Joshua L. , Strain Errol , Agarwala Richa , Musser Steven M. 
Published: May 2024

AbstractWhole-genome sequencing of bacterial pathogens is used by public health agencies to link cases of food poisoning caused by the same source of contamination. The vast majority of these appear to be sporadic cases associated with small contamination episodes and do not trigger investigations. We analyzed clusters of sequenced clinical isolates ofSalmonella,Escherichia coli,Campylobacter, andListeriathat differ by only a small number of mutations to provide a new understanding of the underlying contamination episodes. These analyses provide new evidence that the youngest age groups have greater susceptibility to infection fromSalmonella,Escherichia coli, andCampylobacterthan older age groups. This age bias is weaker for the commonSalmonellaserovar Enteritidis than Salmonella in general. Analysis of these clusters reveals significant regional variations in relative frequencies ofSalmonellaserovars across the United States. A large fraction of the contamination episodes causing sickness appear to have long duration. For example, 50% of theSalmonellacases are in clusters that persist for almost three years. For all four pathogen species, the majority of the cases were part of genetic clusters with illnesses in multiple states and likely to be caused by contaminated commercially distributed foods. The vast majority ofSalmonellacases among infants < 6 months of age appear to be caused by cross-contamination from foods consumed by older age groups or by environmental bacteria rather than infant formula contaminated at production sites.
Genomic loss of GPR108 disrupts AAV transduction in birds
Authors: Nevue Alexander A. , Sairavi Anusha , Huang Samuel J. , Nakai Hiroyuki , Mello Claudio V. 
Published: May 2024

AbstractThe G protein-coupled receptor 108 (GPR108) gene encodes a protein factor identified as critical for adeno-associated virus (AAV) entry into mammalian cells, but whether it is universally involved in AAV transduction is unknown. Remarkably, we have discovered thatGPR108is absent in the genomes of birds and in most other sauropsids, providing a likely explanation for the overall lower AAV transduction efficacy of common AAV serotypes in birds compared to mammals. Importantly, transgenic expression of humanGPR108and manipulation of related glycan binding sites in the viral capsid significantly boost AAV transduction in zebra finch cells. These findings contribute to a more in depth understanding of the mechanisms and evolution of AAV transduction, with potential implications for the design of efficient tools for gene manipulation in experimental animal models, and a range of gene therapy applications in humans.
Combining DNA and protein alignments to improve genome annotation with LiftOn
Authors: Chao Kuan-Hao , Heinz Jakob M. , Hoh Celine , Mao Alan , Shumate Alaina , Pertea Mihaela , Salzberg Steven L 
Published: May 2024

AbstractAs the number and variety of assembled genomes continues to grow, the number of annotated genomes is falling behind, particularly for eukaryotes. DNA-based mapping tools help to address this challenge, but they are only able to transfer annotation between closely-related species. Here we introduce LiftOn, a homology-based software tool that integrates DNA and protein alignments to enhance the accuracy of genome-scale annotation and to allow mapping between relatively distant species. LiftOn’s protein-centric algorithm considers both types of alignments, chooses optimal open reading frames, resolves overlapping gene loci, and finds additional gene copies where they exist. LiftOn can reliably transfer annotation between genomes representing members of the same species, as we demonstrate on human, mouse, honey bee, rice, andArabidopsis thaliana. It can further map annotation effectively across species pairs as far apart as mouse and rat orDrosophila melanogasterandD. erecta.
Using machine learning to dissect host kinases required forLeishmaniainternalization and development
Authors: Wei Ling , Barrie Umaru , Aloisio Gina M. , Khuong Francis T. H. , Arang Nadia , Datta Arani , Kaushansky Alexis , Wetzel Dawn M. 
Published: May 2024

AbstractTheLeishmanialife cycle alternates between promastigotes, found in the sandfly, and amastigotes, found in mammals. When an infected sandfly bites a host, promastigotes are engulfed by phagocytes (i.e., neutrophils, dendritic cells, and macrophages) to establish infection. When these phagocytes die or break down, amastigotes must be re-internalized to survive within the acidic phagolysosome and establish disease. To define host kinase regulators ofLeishmaniapromastigote and amastigote uptake and survival within macrophages, we performed an image-based kinase regression screen using a panel of 38 kinase inhibitors with unique yet overlapping kinase targets. We also targeted inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls by coating them with complement/C3bi or IgG respectively. Through this approach, we identified several putative host kinases that regulate receptor-mediated phagocytosis and/or the uptake ofL. amazonensis. Findings included kinases previously implicated inLeishmaniauptake (such as Src family kinases (SFK), Abl family kinases (ABL1/c-Abl, ABL2/Arg), and spleen tyrosine kinase (SYK)), but we also uncovered many novel kinases. Our methods also predicted host kinases necessary for promastigotes to convert to amastigotes or for amastigotes to survive within macrophages. Overall, our results suggest that the concerted action of multiple interconnected networks of host kinases are needed over the course ofLeishmaniainfection, and that the kinases required for the parasite’s life cycle may differ substantially depending on which receptors are bound and the life cycle stage that is internalized. In addition, using our screen, we identified kinases that appear to preferentially regulate the uptake of parasites over beads, indicating that the methods required forLeishmaniato be internalized by macrophages may differ significantly from generalized phagocytic mechanisms. Our findings are intended to be used as a hypothesis generation resource for the broader scientific community studying the roles of kinases in host-pathogen interactions.
A neuroimaging dataset during sequential color qualia similarity judgments with and without reports
Authors: Hirao Takahiro , Miyamae Mitsuhiro , Matsuyoshi Daisuke , Inoue Ryuto , Takado Yuhei , Obata Takayuki , Higuchi Makoto , Tsuchiya Naotsugu , Yamada Makiko 
Published: May 2024

AbstractRecent neuroscientific research has advanced our understanding of consciousness, yet the connection between specific qualitative aspects of consciousness, known as “qualia,” and particular brain regions or networks remains elusive. Traditional methods that rely on verbal descriptions from participants pose challenges in neuroimaging studies. To address this, our group has introduced a novel “qualia structure” paradigm that leverages exhaustive, structural, and relational comparisons among qualia instead of verbal reports. In this study, we present the first fMRI dataset that captures relational similarity judgments among two out of nine color qualia per trial from 35 participants. This dataset also includes a “no-report” condition in half of the trials to assess the impact of overt reporting. Additionally, each participant’s color discriminability was evaluated with a hue test conducted outside the scanner. Our data offer valuable insights into the brain functions associated with color qualia and contribute to a deeper understanding of the neural foundations of consciousness.
Self-cleaving ribozymes conserved in RNA viruses unveil a new role in protein translation
Authors: López-Galiano María José , Chiba Sotaro , Forgia Marco , Navarro Beatriz , Cervera Amelia , Babaian Artem , Di Serio Francesco , Turina Massimo , de la Peña Marcos 
Published: May 2024

AbstractSmall self-cleaving ribozymes are catalytic RNAs originally discovered in viroid-like agents, which are infectious circular RNAs (circRNAs) postulated as relics of a prebiotic RNA world. In the last decade, however, small ribozymes have also been detected across the tree of life, from bacterial to human genomes, and more recently, in viral agents with circRNA genomes. Here we report the conserved occurrence of small ribozymes within the linear genomes of typical ds and ssRNA viruses from fungi and plants. In most 5’-UTR regions of chrysovirids and fusarivirids, we find conserved type I hammerhead ribozymes (hhrbzs) showing efficient self-cleaving activityin vitroandin vivo. Similar hhrbzs, as well as hepatitis delta and twister ribozymes, were also detected in megabirna-, hypo-, fusagra- and toti-like viruses. These ribozymes occur as isolated motifs but also as close tandem pairs, suggesting that they are involved in the formation of ∼300 nt circRNAs.In vivocharacterization of a chrysovirid hhrbz revealed its unexpected role in protein translation as an internal ribosome entry site (IRES). RNA structural comparison between the hammerhead three-way junction and the core domain of picornavirus IRES elements allow us to suggest that these simple ribozymes may follow a similar strategy to achieve cap-independent translation. We conclude that self-cleaving ribozymes, historically involved in the rolling circle replication of viroid-like agents, have been exapted towards translational functions in linear RNA viruses.
Reconciling Flexibility and Efficiency: Medial Entorhinal Cortex Represents a Compositional Cognitive Map
Authors: Piray Payam , Daw Nathaniel D 
Published: May 2024

AbstractThe influential concept of a cognitive map envisions that the brain builds mental representations of objects, barriers, and goals. This idea has been formalized in a range of computational models that show how such representations can be useful for guiding goal-directed behavior, for instance by planning novel routes to maximize long-run rewards. One key feature of flexible cognitive representations generally is that they exploit compositionality – the ability to build complex structures by recombining simpler parts. However, how this principle plays out in neural representations of cognitive maps and map-based planning remains largely unexplored. Indeed, as we show here, compositionality can be difficult to reconcile with efficient planning: because reuse tends to oppose flexibility, it is challenging to construct a compositional representation of the environment which is also organized in a way that enables generalizability and efficient planning. Here, we propose a novel model for efficiently creating and planning with compositional predictive maps, and further show that it successfully simulates various aspects of response fields in the medial entorhinal cortex, particularly object vector cells and grid cells. The model treats each object as an alteration to a baseline map linked to open space, creating complete predictive maps by combining object-related representations compositionally. Overall, this work provides a comprehensive and realistic model for efficient model learning and model-based planning in animals, and offers insights into the brain processes supporting efficient, flexible planning using compositional predictive maps.
Comparative Analysis of the Techniques for the Determination of Binding Affinity between a Small Molecule Inhibitor and a Protein Target
Authors: Luo Yalan , Chen Yijun 
Published: May 2024

AbstractThe binding affinity constant (KD) between a small molecule inhibitor and a protein target is pivotal parameter for target identification and early drug discovery. Despite the extensive applications of three major techniques, namely SPR, ITC and MST, theKDvalues for a specifically defined binding measured by these techniques are drastically different, which poses a remarkable difficulty to deal with these ambiguous data. Here, we report the evaluation of the accuracy ofKDvalues from SPR, ITC and MST compared with enzyme kinetics. To enable an objective comparison, we theoretically proved that enzyme competitive inhibition constant (Ki) could directly reflect the binding affinity. Using purine nucleoside phosphorylase, its substrate inosine and competitive inhibitor immucillin-H, we determined respectiveKDandKivalues to make a direct comparison. Moreover, we found that theKDvalue measured by SPR is more relevant to itsKivalue. This study highlights the urgent need on the development of new technologies for the determination of binding affinity between small molecule inhibitors and protein targets.
Biological activities and metabolic profile of endophyticBacillus haynesiifromMomordica charantia
Authors: Sharma Garima , Agarwal Surbhi , Bhardwaj Rashmi , Barvkar Vitthal T. , Kumar Vinay , Mathur Vartika 
Published: May 2024

ABSTRACTEndophytes share a complex intimate relationship due to which they are capable of synthesizing metabolites that are either similar or derivative of host bioactive compounds. Such endophytes especially from medicinal plants can be prospected for commercial-scale production of the therapeutic compound. Thus, the study evaluates the antioxidant and anti-inflammatory potential ofMomordica charantiafruit endophyteBacillus haynesiiR2MCFF61, and determines its metabolite profile through LC-Q-TOF-MS for the bioactive compounds produced.B. haynesiiR2MCFF61 showed significant antioxidant and anti-inflammatory potential with increased DPPH scavenging activity in the standard compound and inhibition of protein denaturation respectively. The metabolic profile of this endophyte showed 23 compounds, mostly consisting of metabolites from lipid, phenylpropanoid and triterpenoid pathways.B. haynesiiR2MCFF61 showed production of cucurbitane-triterpenoids namely Momordicoside K, 19-dimethoxycucurbita-5(10),6,22(E),24-tetraen-3β-ol and 23(E)-7β-methoxycucurbita-5,23,25-trien-3β-ol. These compounds are mainly produced byM. charantiafruit and their production by its endophyte is reported for the first time. Thus, these results indicate the promising therapeutic potential ofB. haynesiiR2MCFF61 which can be utilized as a low-cost sustainable source of these bioactive compounds.