bluuebunny/crossref_metadata_2025_split huggingface dataset:
A disease associated mutant reveals how Ltv1 orchestrates RP assembly and rRNA folding of the small ribosomal subunit head
Authors: Blomqvist Ebba K. , Huang Haina , Karbstein Katrin 
Published: July 2023

AbstractRibosomes are complex macromolecules assembled from 4 rRNAs and 79 ribosomal proteins (RPs). Their assembly is organized in a highly hierarchical manner, which is thought to avoid dead-end pathways, thereby enabling efficient assembly of ribosomes in the large quantities needed for healthy cellular growth. Moreover, hierarchical assembly also can help ensure that each RP is included in the mature ribosome. Nonetheless, how this hierarchy is achieved remains unknown, beyond the examples that depend on direct RP-RP interactions, which account for only a fraction of the observed dependencies. Using assembly of the small subunit head and a disease-associated mutation in the assembly factor Ltv1 as a model system, we dissect here how the hierarchy in RP binding is constructed. Our data demonstrate that the LIPHAK-disease-associated Ltv1 mutation leads to global defects in head assembly, which are explained by direct binding of Ltv1 to 5 out of 15 RPs, and indirect effects that affect 4 additional RPs. These indirect effects are mediated by conformational transitions in the nascent subunit that are regulated by Ltv1. Mechanistically, Ltv1 aids the recruitment of some RPs via direct protein-protein interactions, but surprisingly also delays the recruitment of other RPs. Delayed binding of key RPs also delays the acquisition of RNA structure that is stabilized by these proteins. Finally, our data also indicate direct roles for Ltv1 in chaperoning the folding of a key rRNA structural element, the three-helix junction j34-35-38. Thus, Ltv1 plays critical roles in organizing the order of both RP binding to rRNA and rRNA folding, thereby enabling efficient 40S subunit assembly.
The environmentally-regulated interplay between local three-dimensional chromatin organisation and transcription ofproVWXinE. coli
Authors: Rashid Fatema-Zahra M. , Crémazy Frédéric G.E. , Hofmann Andreas , Forrest David , Grainger David C. , Heermann Dieter W. , Dame Remus T. 
Published: July 2023

AbstractNucleoid associated proteins (NAPs) maintain the architecture of bacterial chromosomes and regulate gene expression. Thus, their role as transcription factors may involve three-dimensional chromosome re-organisation. While this model is supported by in vitro studies, direct in vivo evidence is lacking. Here, we use RT-qPCR and 3C-qPCR to study the transcriptional and architectural profiles of the H-NS-regulated, osmoresponsiveproVWXoperon ofEscherichia coliat different osmolarities and provide in vivo evidence for transcription regulation by NAP-mediated chromosome re-modelling in bacteria. We show that activation ofproVWXin response to a hyperosmotic shock involves the destabilization of H-NS-mediated bridges anchored between theproVWXdownstream and upstream regulatory elements (DRE and URE), and between the DRE andygaYthat lies immediately downstream ofproVWX. The re-establishment of these bridges upon adaptation to hyperosmolarity represses the operon. H-NS and H-NS-like proteins are wide-spread amongst bacteria, suggesting that chromosome re-modelling may be a typical feature of transcriptional control in bacteria.
De novogenome assembly and comparative genomics for the colonial ascidianBotrylloides violaceus
Authors: Sumner Jack T. , Andrasz Cassidy L. , Johnson Christine A. , Wax Sarah , Anderson Paul , Keeling Elena L. , Davidson Jean M. 
Published: July 2023

AbstractAscidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian,Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc. short and Oxford Nanopore Technologies long-read sequencing technologies. The resulting assembly is comprised of 831 contigs, has a total length of 121 Mbp, N50 of 1 Mbp and a BUSCO score of 96.1%. Genome annotation identified 13K protein-coding genes. Comparative genomic analysis with other tunicates reveals patterns of conservation and divergence within orthologous gene families even among closely related species. Characterization of the Wnt gene family, encoding signaling ligands involved in development and regeneration, reveals conserved patterns of subfamily presence and gene copy number among botryllids. This supports the use of genomic data from non-model organisms in the investigation of biological phenomena.
Repeated evolution of herbicide resistance inLolium multiflorumrevealed by haplotype-resolved analysis of acetyl-CoA carboxylase
Authors: Brunharo Caio A. C. G. , Tranel Patrick J. 
Published: July 2023

ABSTRACTHerbicide resistance in weeds is one of the greatest challenges in modern food production. The grass speciesLolium multiflorumis an excellent model species to investigate convergent evolution under similar selection pressure because populations have repeatedly evolved resistance to many herbicides, utilizing a multitude of mechanisms to neutralize herbicide damage. In this work, we investigated the gene that encodes acetyl-CoA carboxylase (ACCase), the target-site of the most successful herbicide group available for grass weed control. We sampledL. multiflorumpopulations from agricultural fields with history of intense herbicide use, and studied their response to three ACCase-inhibiting herbicides under controlled conditions. To elucidate the mechanisms of herbicide resistance and the genetic relationship among sampled populations, we resolved the haplotypes of 97 resistant and susceptible individuals by performing an amplicon-seq analysis using long-read DNA sequencing technologies, focusing on the DNA sequence encoding the carboxyl-transferase domain of ACCase. Our dose-response data indicated the existence of many, often unpredictable, resistance patterns to ACCase-inhibiting herbicides, where populations exhibited as much as 37-fold reduction in herbicide response. The majority of the populations exhibited resistance to all three herbicides studied. Phylogenetic and molecular genetic analyses revealed multiple evolutionary origins of resistance-endowingACCasehaplotypes, as well as widespread admixture in the region regardless of cropping system. The amplicons generated were very diverse, with haplotypes exhibiting 26 to 110 polymorphisms. Polymorphisms included insertions and deletions 1-31 bp in length, none of which were associated with the resistance phenotype. We also found evidence that some populations have multiple mechanisms of resistance. Our results highlight the astounding genetic diversity inL. multiflorumpopulations, and the potential for convergent evolution of herbicide resistance across the landscape that challenges weed management and jeopardizes sustainable weed control practices. We provide an in-depth discussion of the evolutionary and practical implications of our results.
MicroRNA-375 is induced during astrocyte-to-neuron reprogramming and promotes survival of reprogrammed neurons when overexpressed
Authors: Chen Xuanyu , Sokirniy Ivan , Wang Xin , Jiang Mei , Mseis-Jackson Natalie , Williams Christine , Mayes Kristopher , Jiang Na , Puls Brendan , Du Quansheng , Shi Yang , Li Hedong 
Published: July 2023

ABSTRACTWhile astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. MicroRNAs (miRNAs), as post-transcriptional regulators of gene expression, play crucial roles during development and under various pathological conditions. To understand the function of miRNAs during AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activates essential neuronal genes to initiate reprogramming process but also induces miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets,neuronal ELAVLgenes (nELAVLs), which encode a family of RNA-binding proteins and are also upregulated by NeuroD1. We further showed that manipulating miR-375 level regulatesnELAVLsexpression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLsare also induced by reprogramming factors Neurog2 and ASCL1 in HA suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improves NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA even in cultures treated with the chemotherapy drug Cisplatin. Moreover, miR-375 overexpression doesn’t appear to compromise maturation of the reprogrammed neurons in long term HA cultures. Lastly, overexpression of miR-375-refractory ELAVL4 induces apoptosis and reverses the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrate a neuro-protective role of miR-375 during NeuroD1-mediated AtN reprogramming and suggest a strategy of combinatory overexpression of NeuroD1 and miR-375 for improving neuronal reprogramming efficiency.
TBSS++: A novel computational method for Tract-Based Spatial Statistics
Authors: Karimi Davood , Kebiri Hamza , Gholipour Ali 
Published: July 2023

AbstractDiffusion-weighted magnetic resonance imaging (dMRI) is widely used to assess the brain white matter. One of the most common computations in dMRI involves cross-subject tract-specific analysis, whereby dMRI-derived biomarkers are compared between cohorts of subjects. The accuracy and reliability of these studies hinges on the ability to compare precisely the same white matter tracts across subjects. This is an intricate and error-prone computation. Existing computational methods such as Tract-Based Spatial Statistics (TBSS) suffer from a host of shortcomings and limitations that can seriously undermine the validity of the results. We present a new computational framework that overcomes the limitations of existing methods via (i) accurate segmentation of the tracts, and (ii) precise registration of data from different subjects/scans. The registration is based on fiber orientation distributions. To further improve the alignment of cross-subject data, we create detailed atlases of white matter tracts. These atlases serve as an unbiased reference space where the data from all subjects is registered for comparison. Extensive evaluations show that, compared with TBSS, our proposed framework offers significantly higher reproducibility and robustness to data pertur-bations. Our method promises a drastic improvement in accuracy and reproducibility of cross-subject dMRI studies that are routinely used in neuroscience and medical research.
Genome assembly ofHibiscus sabdariffaL. provides insights into biosynthetic pathways of medicinal natural products
Authors: Kim Taein , Lee Jeong Hun , Seo Hyo Hyun , Moh Sang Hyun , Choi Sung Soo , Kim Jun , Kim Sang-Gyu 
Published: July 2023

AbstractHibiscus sabdariffaL. is a widely cultivated herbaceous plant with diverse applications in food, tea, fiber, and medicine. In this study, we present a high-quality genome assembly ofH. sabdariffausing more than 33 Gbps of high-fidelity (HiFi) long-read sequencing data at 20X coverage. The primary assembly and haplotype-resolved genomes exhibit an N50 contig length of 26.25 Mbps, 11.96 Mbps, and 14.50 Mbps, with a coverage of 141.3%, 86.0%, and 88.6%, respectively. By aligning 26 Gbps of total RNA sequencing data (PE100) extracted from leaves, we predicted 154k, 79k, and 87k genes in the respective genome. The completeness of the genomes and predicted genes was confirmed by benchmarking universal single-copy orthologs analysis on a eudicots_odb10 database, with a 99.3% complete rate for the primary assembly. The high-quality genome resource allowed the construction of genetic networks for phenylpropanoid and flavonoid metabolism, thereby facilitating the identification of candidate genes involved in the biosynthesis of key intermediates for roselle-specific medicinal natural products. Comprehensive genomic and functional analysis opens avenues for further exploration and application of valuable natural products derived fromH. sabdariffa.
The heterogeneity and effect of diabetes and hypertension on spectral characteristics of vasomotion
Authors: Zhao Liangjing , Liu Shuhong , Liu Yang , Tang Hui 
Published: July 2023

AbstractVasomotion refers to the spontaneous oscillation of blood vessels within a frequency range of 0.01 to 1.6 Hz. Various disease states, including hypertension and diabetes, have been associated with alterations in vasomotion at the finger, indicating potential impairment of skin microcirculation. Due to the non-linear nature of human vasculature, the modification of vasomotion may vary across different locations for different diseases. In this study, Laser Doppler Flowmetry was used to measure blood flow motion at acupoints LU8, LU5, SP6, and PC3 among 49 participants with or without diabetes and/or hypertension. Fast Fourier Transformation was used to analyze noise type while Hilbert-Huang Transformation and wavelet analysis were applied to assess Signal Noise Ratio (SNR) results. Statistical analysis revealed that different acupoints exhibit distinct spectral characteristics of vasomotion not only among healthy individuals but also among patients with diabetes and hypertension. The results showed strong heterogeneity of vasomotion among blood vessels, indicating that the vasomotion measured at a certain point may not reflect the real status of microcirculation.
Hyperparameter optimisation in differential evolution using Summed Local Difference Strings, a rugged but easily calculated landscape for combinatorial search problems
Authors: Pannu Husanbir Singh , Kell Douglas B. 
Published: July 2023

AbstractWe analyse the effectiveness of differential evolution hyperparameters in large-scale search problems, i.e. those with very many variables or vector elements, using a novel objective function that is easily calculated from the vector/string itself. The objective function is simply the sum of the differences between adjacent elements. For both binary and real-valued elements whose smallest and largest values are min and max in a vector of length N, the value of the objective function ranges between 0 and(N-1) × (max-min)and can thus easily be normalised if desired. This provides for a conveniently rugged landscape. Using this we assess how effectively search varies with both the values of fixed hyperparameters for Differential Evolution and the string length. String length, population size and generations for computational iterations have been studied. Finally, a neural network is trained by systematically varying three hyper-parameters, viz population (NP), mutation factor (F) and crossover rate (CR), and two output target variables are collected (a) median and (b) maximum cost function values from 10-trial experiments. This neural system is then tested on an extended range of data points generated by varying the three parameters on a finer scale to predict bothmedianandmaximumfunction costs. The results obtained from the machine learning model have been validated with actual runs using Pearson’s coefficient to justify the reliability to motivate the use of machine learning techniques over grid search for hyper-parameter search for numerical optimisation algorithms. The performance has also been compared with SMAC3 and OPTUNA in addition to grid search and random search.
Long-term memory formation depends on an astrocyte-to-neuron H2O2signaling
Authors: Rabah Yasmine , Sagar Nisrine , Pasquer Laure , Plaçais Pierre-Yves , Preat Thomas 
Published: July 2023

AbstractAstrocytes interact with neurons during cognitive processes1. In particular, astrocytes help neurons to fight oxidative stress2, a needed function since active neurons are prone to reactive oxygen species (ROS) damage due to their high mitochondrial activity and relatively poor antioxidant defenses3. ROS also play major physiological functions4,5, but it remains unknown how neuronal ROS signaling is activated during memory formation and if astrocytes play a role in that process. We discovered in Drosophila an astrocyte-to-neuron H2O2signaling cascade essential for long-term memory formation. Stimulation of astrocytes by acetylcholine induces an intracellular calcium increase that triggers the formation of extracellular O2°−by astrocytic NADPH oxidase. Superoxide dismutase 3 secreted by astrocytes converts O2°−into H2O2, which is imported into neurons of the olfactory memory center (the mushroom body), as revealed byin vivoH2O2imaging using an ultrasensitive sensor. Importantly, SOD3 activity requires Cu2+, which we show is delivered by the neuronal Amyloid Precursor Protein. Furthermore, we found that human amyloid-ß peptide, involved in Alzheimer’s disease, inhibits the astrocytic cholinergic receptor and hampers memory formation by preventing H2O2import into neurons. These findings could have major implications for the understanding of Alzheimer’s disease etiology, as soluble synaptic Aß42 correlates better with the pattern of cognitive decline in AD than amyloid plaques6, and since early pathology in cholinergic neurons of the basal forebrain predicts memory defects7,8.
Differential acclimation kinetics of the two forms of Type IV chromatic acclimaters occurring in marineSynechococcuscyanobacteria
Authors: Dufour Louison , Gouriou Bastian , Clairet Julia , Ratin Morgane , Garczarek Laurence , Partensky Frédéric 
Published: July 2023

ABSTRACTSynechococcusis one of two most abundant phytoplanktonic organisms of the Ocean and also displays the widest variety of pigmentation of all marine oxyphotrophs, which makes it ideally suited to colonize the variety of spectral niches occurring in the upper-lit layer of oceans. SevenSynechococcuspigment types (PTs) have been described based on the composition and chromophorylation of their light-harvesting complexes, called phycobilisomes (PBS). The most sophisticated and abundantSynechococcusPT (3d) gathers cells capable of Type IV chromatic acclimation (CA4), i.e. to reversibly modify the ratio of the blue light-absorbing phycourobilin (PUB) to the green light-absorbing phycoerythrobilin (PEB) in PBS in order to match the ambient light color. Although two genetically distinct types of CA4-capable strains, so-called PTs 3dA and 3dB, have been evidenced and found to be equally abundant in the Ocean, reasons for their prevalence in naturalSynechococcuspopulations remain obscure. Here, acclimation experiments in different blue to green ratios of representatives of these two PTs showed that in mixed blue-green light conditions, PT 3dB strains displayed significantly higher PUB:PEB ratios than their PT 3dA counterparts. Thus, PTs 3dA and 3dB seem to differ in the ratio of blue to green light required to trigger the CA4 process. Furthermore, shift experiments between 100% BL and 100% GL conditions, and conversely, also revealed discrepancies in the acclimation pace between the two types of chromatic acclimaters, which may explain their co-occurrence in some blue green light niches.
Remodelling of cytoskeleton and plasma membrane proteins contributes to drought sensitivity of Arabidopsisrhd2mutant
Authors: Takáč Tomáš , Kuběnová Lenka , Šamajová Olga , Dvořák Petr , Haberland Jan , Bundschuh Sebastian T. , Tomančák Pavel , Ovečka Miroslav , Šamaj Jozef 
Published: July 2023

AbstractNADPH oxidases are enzymes localised in the plasma membrane and emitting superoxide to the extracellular space. By production of superoxide as one type of reactive oxygen species (ROS), they exert pleiotropic functions in plant development and various stress responses.Arabidopsis thalianaRESPIRATORY BURST OXIDASE HOMOLOG PROTEIN C/ROOT HAIR DEFECTIVE 2 (AtRBOHC/RHD2) is an NADPH oxidase with preferential gene expression in roots. Polar localisation and ROS production by this enzyme are essential for root hair elongation. However, the proteome-wide and physiological consequences ofRBOHC/RHD2mutations are unknown. To find out potential new functions of AtRBOHC/RHD2, we employed a differential proteomic analysis of Arabidopsisrhd2-1mutant, carrying a loss-of-function mutation inRBOHC/RHD2. Proteomic analyses that were validated with independent biochemical, phenotypical and advanced microscopy methods, showed quantitative deregulation of proteins involved in abiotic and biotic stress response, metabolism, vesicular transport and cell wall modification. Considerable differences in the differential proteomes between roots and above-ground parts were found in the mutant. The altered abundance of aquaporins and homeostasis of transmembrane pumps and transporters most likely determine the higher sensitivity of Arabidopsisrhd2-1mutant to drought.HighlightProteomics and advanced microscopy reveal that the drought sensitivity of Arabidopsis mutant inROOT HAIR DEFECTIVE 2is linked to altered homeostasis of plasma membrane proteins and cytoskeleton remodelling.
fastlin: an ultra-fast program forMycobacterium tuberculosiscomplex lineage typing
Authors: Derelle Romain , Lees John , Phelan Jody , Lalvani Ajit , Arinaminpathy Nimalan , Chindelevitch Leonid 
Published: July 2023

AbstractLineage typing of theMycobacterium tuberculosiscomplex (MTBC) has evolved from traditional phenotypic methods to advanced molecular and genomic techniques. In this study we present fastlin, a bioinformatics tool designed for rapid MTBC lineage typing. Fastlin utilises an ultra-fast alignment-free approach to detect previously identified barcode single nucleotide polymorphisms (SNPs) associated with specific MTBC lineages directly from fastq files. In a comprehensive benchmarking against existing tools, fastlin demonstrated high accuracy and significantly faster running times. Analysis of large MTBC datasets revealed fastlin’s capability not only to predict MTBC lineages, but also to detect mixed-lineage strain mixtures and estimate their proportions. Fastlin offers a user-friendly and efficient solution for MTBC lineage typing, complementing existing tools and facilitating large-scale analysis.
The distribution of fitness effects of plasmid pOXA-48 in clinical enterobacteria
Authors: Fernandez-Calvet Ariadna , Toribio-Celestino Laura , Valle Aida Alonso-del , Sastre-Dominguez Jorge , Valdes-Chiara Paula , Millan Alvaro San , DelaFuente Javier 
Published: July 2023

AbstractAntimicrobial resistance (AMR) in bacteria is a major public health problem. The main route for AMR acquisition in clinically important bacteria is the horizontal transfer of plasmids carrying resistance genes. AMR plasmids allow bacteria to survive antibiotics, but they also entail physiological alterations in the host cell. Multiple studies over the last years indicate that these alterations can translate into a fitness cost when antibiotics are absent. However, due to technical limitations, most of these studies are based on analysing new associations between plasmids and bacteria generatedin vitro, and we know very little about the effects of plasmids in their native bacterial hosts. In this study, we used a CRISPR-Cas9-tool to selectively cure plasmids from clinical enterobacteria to overcome this limitation. Using this approach, we were able to study the fitness effects of the carbapenem resistance plasmid pOXA-48 in 35 pOXA-48-carrying isolates recovered from hospitalised patients. Our results revealed that pOXA-48 produces variable effects across the collection of wild type enterobacterial strains naturally carrying the plasmid, ranging from fitness costs to fitness benefits. Importantly, the plasmid was only associated with a significant fitness reduction in 4 out of 35 clones, and produced no significant changes in fitness in the great majority of isolates. Our results suggest that plasmids produce neutral fitness effects in most native bacterial hosts, helping to explain the great prevalence of plasmids in natural microbial communities.