bluuebunny/crossref_metadata_2025_split huggingface dataset:
TB-annotator: a scalable web application that allowsin-depthanalysis of very large sets of publicly availableMycobacterium tuberculosiscomplex genomes
Authors: Senelle Gaetan , Guyeux Christophe , Refrégier Guislaine , Sola Christophe 
Published: June 2023

AbstractTuberculosis continues to be one of the most threatening bacterial diseases in the world. However, we currently have more than 160,000 Short Read Archives (SRAs) ofMycobacterium tuberculosiscomplex. Such a large amount of data should help to the understanding and the fight against this bacterium. To accomplish this, it would be necessary to thoroughly and comprehensively examine this significant mass of data. This is what TB-Annotator proposes to do, combining a database containing all the diversity of these 160,000 SRAs (at least, SRAs with a reasonable read size and quality), and a fully featured analysis platform to explore and query such a large amount of data. The objective of this article is to present this platform centered on the key notion of exclusivity, to show its numerous capacities (detection of single nucleotide variants, insertion sequences, deletion regions, spoligotyping, etc.) and its general functioning. We will compare TB-Annotator to existing tools for the study of tuberculosis, and show that its objectives are original and have no equivalent at present. The database on which it is based will be presented, with the numerous advanced search queries and screening capacities it offers, and the interest and originality of its phylogenetic tree navigation interface will be detailed. We will end this article with examples of the achievements made possible by the TB-Annotator, followed by avenues for future improvement.
The dynamics of phage predation on a microcolony
Authors: Eriksen Rasmus Skytte , Larsen Frej , Svenningsen Sine Lo , Sneppen Kim , Mitarai Namiko 
Published: June 2023

AbstractPhage predation is an important factor for controlling the bacterial biomass. At face value, dense microbial habitats are expected to be vulnerable to phage epidemics due to the abundance of fresh hosts immediately next to any infected bacteria. Despite this, the bacterial microcolony is a common habitat for bacteria in nature. Here we experimentally quantify the fate of microcolonies ofEscherichia coliexposed to virulent phageT4. It has been proposed that the outer bacterial layers of the colony will shield the inner layers from the phage invasion and thereby constrain the phage to the colony’s surface. We develop a dynamical model that incorporates this shielding mechanism and fits the results with experimental measurements to extract important phage-bacteria interaction parameters. The analysis suggests that, while the shielding mechanism delays phage attack,T4phage are able to diffuse so deep into the dense bacterial environment that colony level survival of the bacterial community is challenged.SignificanceThe shielding mechanism of bacterial microcolonies against phage invasion has been experimentally quantified, and the result was analyzed by using a mathematical model. The analysis suggests that while forming a dense colony delays phage attack by limiting the infection closer to the colony surface,T4phage can diffuse so deep into the dense bacterial environment that colony-level survival of the bacterial community is challenged. This finding highlights the importance of the interplay between the phage infection dynamics and the physical structure of bacterial colonies in controlling the microbial population.
Rewiring of the epigenome and chromatin architecture by retinoic acid signaling during zebrafish embryonic development
Authors: Moreno-Oñate Marta , Gallardo-Fuentes Lourdes , Martínez-García Pedro M. , Naranjo Silvia , Jiménez-Gancedo Sandra , Gómez-Skarmeta José L. , Tena Juan J. , Santos-Pereira José M. 
Published: June 2023

AbstractBackgroundRetinoic acid (RA) functions as a ligand for the nuclear RA receptors (RARs), which regulate the expression of target genes by binding to RA response elements. RA signaling is required for multiple processes during chordate embryonic development, such as body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling duringin vivoembryonic development.ResultsHere we stimulate the RA pathway during development by treating zebrafish embryos with all-trans-RA (atRA), the most abundant form of RA, and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which RA signaling control target gene expression. We find that RA signaling is involved in anterior/posterior patterning and development of the central nervous system, participating in the transition from pluripotency to differentiation. atRA treatment also induces alterations in chromatin accessibility during early development and promotes chromatin binding of RARαa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions that are consistent with target gene expression. This is illustrated by the specific induction of anterior HoxB genes by RARs, among other examples.ConclusionsAltogether, our findings identify genome-wide targets of RA signaling during embryonic development and provide a molecular mechanism by which developmental signaling pathways regulate the expression of target genes by altering chromatin topology.
Mechanical loading of the Achilles tendon during different rehabilitation exercises: A cross sectional observational study
Authors: New Paul , Wood Lianne 
Published: June 2023

AbstractBackgroundAchilles tendon injuries are common in active populations and heel raising exercises are commonly used in tendon rehabilitation programmes. This study compared characteristics of force occurring within the healthy Achilles tendon during two different types of exercise conditions that can be used in Achilles tendon rehabilitation.MethodA cross-sectional, observational study was conducted to compare force fluctuations occurring within the Achilles tendon during two different types of heel raising exercise. All subjects performed firstly, a set of traditional eccentric heel drops (HD) and secondly an adapted walking drill (WD), and results were compared. 13 Healthy subjects were recruited from staff and post graduate students as a sample of convenience from the biomechanics department at the University of Bath. Tendon forces were calculated using a combination of data collected from force plate, motion analysis and real time ultrasound.ResultsFluctuations in force were seen in all subjects in both exercise conditions. The HD condition produced a statistically significant increase in force fluctuations compared to the WD condition (p<0.001).ConclusionThis study shows that force fluctuations can be stimulated at different levels during functional movement patterns and exercise conditions. Therefore, exercise routines can be tailored to meet individual needs and the stage of the pathology. These findings may have implications for exercise progressions in the rehabilitation of Achilles tendon disorders. Future research is needed determine if differences in tendon force fluctuations correlate with pathology.Summary StatementThis study is of interest to clinicians, exercise professionals and researchers with an interest in the study of Achilles tendon biomechanics and the management of tendon injuries.
Targeting staphylococcal cell-wall biosynthesis protein FemX through steered molecular dynamics and drug-repurposing approach
Authors: Rahman Shakilur , Nath Subham , Mohan Utpal , Das Amit Kumar 
Published: June 2023

AbstractStaphylococcus aureus-mediated infection is a serious threat in this antimicrobial-resistant world.S. aureushas become a ‘superbug’ by challenging conventional as well as modern treatment strategies. Nowadays, drug repurposing has become a new trend for the discovery of new drug molecules. This study focuses on evaluating FDA-approved drugs that can be repurposed againstS. aureusinfection. Steered molecular dynamics (SMD) has been performed for Lumacaftor and Olaparib against staphylococcal FemX to understand their binding to the active site. A time-dependent external force or rupture has been applied to the ligands to calculate the force required to dislocate the ligand from the binding pocket. SMD analysis indicates that Lumacaftor has a high affinity for the substrate binding pocket in comparison to Olaparib. Umbrella sampling exhibits that Lumacaftor possesses a higher free energy barrier to displace it from the ligand-binding site. The bactericidal activity of Lumacaftor and Olaparib has been tested, and it shows that Lumacaftor has shown moderate activity along with biofilm inhibition potential (MIC value with conc. 128 μg/mL). Pharmacokinetic and toxicology evaluations indicate that Lumacaftor has higher pharmacokinetic potential with lower toxicity. This is the first experimental report where staphylococcal FemX has been targeted for the discovery of new drugs. It is suggested that Lumacaftor may be a potential lead molecule againstS. aureus.
Long noncoding RNAs emerge from transposon-derived antisense sequences and may contribute to infection stage-specific transposon regulation in a fungal phytopathogen
Authors: Qian Jiangzhao , Ibrahim Heba M. M. , Erz Myriam , Kümmel Florian , Panstruga Ralph , Kusch Stefan 
Published: June 2023

AbstractThe genome of the obligate biotrophic phytopathogenic barley powdery mildew fungusBlumeria hordeiis inflated due to highly abundant and possibly active transposable elements (TEs). In the absence of the otherwise common repeat-induced point mutation transposon defense mechanism, noncoding RNAs could be key for regulating the activity of TEs and coding genes during the pathogenic life cycle. We performed time-course whole-transcriptome shotgun sequencing (RNA-seq) of total RNA derived from infected barley leaf epidermis at various stages of fungal pathogenesis and observed significant transcript accumulation and time point-dependent regulation of TEs inB. hordei. Using a manually curated consensus database of 344 TEs, we discovered phased small RNAs mapping to 104 consensus transposons, suggesting that RNA interference contributes significantly to their regulation. Further, we identified 5,127 long noncoding RNAs (lncRNAs) genome-wide inB. hordei, of which 823 originated from the antisense strand of a TE. Co-expression network analysis of lncRNAs, TEs, and coding genes throughout the asexual life cycle ofB. hordeipoints at extensive positive and negative co-regulation of lncRNAs, subsets of TEs and coding genes. Our work suggests that similar to mammals and plants, fungal lncRNAs support the dynamic modulation of transcript levels, including TEs, during pivotal stages of host infection. The lncRNAs may support transcriptional diversity and plasticity amid loss of coding genes in powdery mildew fungi and may give rise to novel regulatory elements and virulence peptides, thus representing key drivers of rapid evolutionary adaptation to promote pathogenicity and overcome host defense.
Charophytic Green Algae encode ancestral Pol IV/Pol V subunits and a CLSY/DRD1 homolog
Authors: Chakraborty Tania , Trujillo Joshua T. , Kendall Timmy , Mosher Rebecca A. 
Published: June 2023

AbstractIn flowering plants, euchromatic transposons are transcriptionally silenced by RNA-directed DNA methylation (RdDM), a small RNA-guidedde novomethylation pathway. RdDM requires the activity of the RNA Polymerase (Pol) IV and V, which produce small RNA precursors and non-coding targets of small RNAs, respectively. These polymerases are distinguished from Pol II by multiple plant-specific paralogous subunits. Most RdDM components are present in all land plants, and some have been found in the Charophytic green algae (CGA), a paraphyletic group that is sister to land plants. However, the evolutionary origin of key RdDM components, including the two largest subunits of Pol IV and Pol V, remains unclear. Here we show that multiple lineages of CGA encode a single-copy precursor of the largest subunits of Pol IV and Pol V, resolving the two presumed duplications in this gene family. We further demonstrate the presence of a Pol V-like C-terminal domain, suggesting that the earliest form of RdDM utilized a single Pol V-like polymerase. Finally, we reveal that CGAs encode a single CLSY/DRD1-type chromatin remodeling protein, further supporting the presence of a single specialized polymerase in CGA RdDM.
SARS-CoV-2 Envelope protein alters calcium signaling via SERCA interactions
Authors: Berta Blanka , Tordai Hedvig , Lukács Gergely L. , Papp Béla , Enyedi Ágnes , Padányi Rita , Hegedűs Tamás 
Published: June 2023

AbstractThe clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor, however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca2+homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirmed that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca2+reload. Structural modeling and molecular dynamics of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.
Reduced mammillary body volume in individuals with a schizophrenia diagnosis: an analysis of the COBRE data set
Authors: Milczarek Michal M. , Gilani Syed I. A. , Lequin Maarten H. , Vann Seralynne D. 
Published: June 2023

AbstractWhile the frontal cortices and medial temporal lobe are well-associated with schizophrenia, the involvement of wider limbic areas is less clear. The mammillary bodies are important for both complex memory formation and anxiety and are implicated in several neurological disorders that present with memory impairments. However, little is known about their role in schizophrenia. Post-mortem studies have reported both a loss of neurons in the mammillary bodies but also reports of increased mammillary body volume. The findings fromin vivoMRI studies have also been mixed, but studies have typically only involved small sample sizes. To address this, we acquired mammillary body volumes from the open-source COBRE dataset, where we were able to manually measure the mammillary bodies in 72 individuals with a schizophrenia diagnosis and 74 controls. Participant age ranged from 18-65. We found the mammillary bodies to be smaller in the patient group, across both hemispheres, after accounting for the effects of total brain volume and gender. Hippocampal volumes, but not subiculum or total grey matter volumes, were also significantly lower in patients. Given the importance of the mammillary bodies for both memory and anxiety, this atrophy could contribute to the symptomology in schizophrenia.
An adapted MS2-MCP system to visualize endogenous cytoplasmic mRNA with live imaging inCaenorhabditis elegans
Authors: Tocchini Cristina , Mango Susan E. 
Published: June 2023

AbstractLive imaging of RNA molecules constitutes an invaluable means to track the dynamics of mRNAs, but live imaging inCaenorhabditis eleganshas been difficult to achieve. Endogenous transcripts have been observed in nuclei, but endogenous mRNAs have not been detected in the cytoplasm, and functional mRNAs have not been generated. Here, we have adapted live imaging methods to visualize mRNA in embryonic epithelial cells. We have tagged endogenous transcripts with MS2 hairpins in the 3’ Untranslated Region (UTR) and visualized them after adjusting MS2 Coat Protein (MCP) expression. A reduced number of these transcripts accumulate in the cytoplasm, leading to loss-of-function phenotypes. In addition, mRNAs fordlg-1fail to associate with the adherens junction, as observed for the endogenous mRNA. These defects are reversed by inactivating the nonsense-mediated decay pathway. RNA accumulates in the cytoplasm,dlg-1associates with the adherens junction, and mutant phenotypes are rescued. These data suggest that MS2 repeats can induce the degradation of endogenous targets and alter the cytoplasmic distribution. Although our focus is RNAs expressed in epithelial cells during morphogenesis, this method can likely be applied to other cell types and stages.Summary statementAn adapted MS2-MCP method to tag endogenous transcripts inC. elegansembryos for live imaging without affecting mRNA stability.
Neural Mechanisms of Creative Problem Solving - From Representational Change to Memory Formation
Authors: Becker Maxi , Sommer Tobias , Cabeza Roberto 
Published: June 2023

ABSTRACTDespite the need for innovative solutions to contemporary challenges, the neural mechanisms driving creative problem-solving, including representational change and its relation to memory, still remain largely unknown. We focused on the powerful creative process of insight, wherein rapid knowledge reorganisation and integration—termed representational change—yield solutions that evoke suddenness, certainty, positive emotion, and enduring memory. We posit that this process manifests as stronger shifts in activation patterns within brain regions housing solution-relevant information, including the visual cortex for visual problems, alongside regions linked to feelings of emotion, suddenness and subsequent memory. Our findings substantiate these hypotheses, revealing stronger representational changes in visual cortex, conjoined with activations in the amygdala and hippocampus—forming an interconnected network. Importantly, the representational change and hippocampal effects serve as predictive markers of subsequent memory. This study provides evidence of an integrated insight mechanism influencing memory. Implications extend to education, emphasising the significance of discovery-based learning approaches for boosting knowledge retention.
Mitogenome sequences of domestic cats demonstrate lineage expansions and dynamic mutation processes in a mitochondrial minisatellite
Authors: Patterson Emily , Lall Gurdeep Matharu , Neumann Rita , Ottolini Barbara , Batini Chiara , Sacchini Federico , Foster Aiden P. , Wetton Jon H. , Jobling Mark A. 
Published: June 2023

AbstractAs a population genetic tool, mitochondrial DNA is commonly divided into the ∼1-kb control region (CR), in which single nucleotide variant (SNV) diversity is relatively high, and the coding region, in which selective constraint is greater and diversity lower, but which provides an informative phylogeny. In some species, the CR contains variable tandemly repeated sequences that are understudied due to heteroplasmy. Domestic cats (Felis catus) have a recent origin and therefore traditional CR-based analysis of populations yields only a small number of haplotypes. To increase resolution we used Nanopore sequencing to analyse 119 cat mitogenomes via a long-amplicon approach. This greatly improves discrimination (from 15 to 87 distinct haplotypes) and defines a phylogeny showing similar starlike topologies within all cat haplogroups, likely reflecting post-domestication expansion. We sequenced RS2, a CR tandem array of 80-bp repeat units, placing RS2 array structures within the phylogeny and increasing overall haplotype diversity. Repeat number varies between 3 and 12 (median: 4) with over 30 different repeat unit types differing largely by SNVs. Five SNVs show evidence of independent recurrence within the phylogeny, and seven are involved in at least 11 instances of rapid spread along repeat arrays within haplogroups. In defining mitogenome variation our study provides key information for the forensic genetic analysis of cat hair evidence, and for the first time a phylogenetically informed picture of tandem repeat variation that reveals remarkably dynamic mutation processes at work in the mitochondrion.
Evaluating key evidence and formulating regulatory alternatives regarding the UK’s Hunting Trophies (Import Prohibition) Bill
Authors: Challender Dan , ’t Sas-Rolfes Michael , Dickman Amy , Hare Darragh , Hart Adam , Hoffmann Michael , Mallon David , Mandisodza-Chikerema Roseline , Roe Dilys 
Published: June 2023

AbstractPublic policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UK’s role in international hunting trophy trade by analyzing CITES trade data for 2000-2021 and 2015-2021. For CITES-listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature Red List of Threatened Species to determine whether hunting designated as “trophy hunting” is i) likely a major threat contributing to species being of elevated conservation concern, ii) likely or possibly causing localized declines, or iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Government’s impact assessment of the bill. In 2000-2021 an estimated 3494 hunting trophies from 73 CITES-listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), i.e. individual animals. Imports involved 158.86 ± 66.53 (mean ± SD) trophies/year (115.83 ± 32.27 WOEs/year). In 2015-2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of nine species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options.