bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scribe: next-generation library searching for DDA experiments
Authors: Searle Brian C. , Shannon Ariana E. , Wilburn Damien Beau 
Published: January 2023

ABSTRACTSpectrum library searching is a powerful alternative to database searching for data dependent acquisition experiments, but has been historically limited to identifying previously observed peptides in libraries. Here we present Scribe, a new library search engine designed to leverage deep learning fragmentation prediction software such as Prosit. Rather than relying on highly curated DDA libraries, this approach predicts fragmentation and retention times for every peptide in a FASTA database. Scribe embeds Percolator for FDR correction and an interference tolerant label-free quantification integrator to enable an end-to-end proteomics workflow. By leveraging expected relative fragmentation and retention time values, we find that library searching with Scribe can outperform traditional database searching tools, both in terms of sensitivity and quantitative precision. Scribe and its graphical interface are easy to use, freely accessible, and fully open source.
Assessment of structural behaviour of new L-asparaginase and SAXS data-based evidence for catalytic activity in its monomeric form
Authors: Mihooliya Kanti N. , Nandal Jitender , Kalidas Nidhi , Ashish  , Chand Subhash , Verma Dipesh K. , Bhattacharyya Mani S. , Sahoo Debendra K. 
Published: January 2023

ABSTRACTThe present study reports the structural and functional characterization of a new glutaminase-free recombinant L-asparaginase (PrASNase) from Pseudomonas resinovorans IGS-131. PrASNase showed substrate specificity to L-asparagine, and its kinetic parameters, Km, Vmax, and kcatwere 9.49×10-3M, 25.13 IUmL-1min-1, and 3.01×103s-1, respectively. The CD spectra showed that PrASNase consists of 30.9% α-helix and 69.1% other structures in its native form. FTIR was used for the functional characterization, and molecular docking predicted that the substrate interacts with serine, alanine, and glutamine in the binding pocket of PrASNase. Different from known asparaginases, structural characterization by small-angle X-ray scattering (SAXS) and analytical ultracentrifugation (AUC) unambiguously revealed PrASNase to exist as a monomer in solution at low temperatures and oligomerized to a higher state with temperature rise. Through SAXS studies and enzyme assay, PrASNase was found to be mostly monomer and catalytically active at 37°C. Furthermore, this glutaminase-free PrASNase showed killing effects against WIL2-S and TF-1.28 cells with IC50of 7.4 µg.mL-1and 5.6 µg.mL-1, respectively. This is probably the first report with significant findings of fully active L-asparaginase in monomeric form using SAXS and AUC and demonstrates the potential of PrASNase in inhibiting cancerous cells, making it a potential therapeutic candidate.HIGHLIGHTSA new L-asparaginase (PrASNase) was structurally and functionally characterized.SAXS revealed PrASNase is functionally active in monomeric form and oligomerizes with temperature rise.Monomeric PrASNase showed an IC50value of 7.4 and 5.6 µg mL-1against WIL2-S and TF-1.28 cells.Cytotoxicity of PrASNase against leukemic cell lines showed its potential as a biotherapeutic.GRAPHICAL ABSTRACT
Multi-Criteria Ambulance Location Problem: better to treat some fast, or more in time?
Authors: Münch Johanna , Leithäuser Neele , Moos Michael , Werner Jennifer , Scherer Guido 
Published: January 2023

AbstractFor the location optimization of several ambulance stations, we outline a multi-criteria integer program to maximize the reached population within different time bounds. This technique is based on a realistic driving time estimation for ambulances on a detailed road network. The results show that, depending on which time bound is more valued, ambulance stations are more likely to be located in urban areas or evenly distributed across the study region. We used this model for real-world studies in Southwest Germany, where several ambulance station locations were optimized simultaneously.
Molecular characterization of nervous system organization in the hemichordateSaccoglossus kowalevskii
Authors: Andrade Lopéz José M. , Pani Ariel M. , Wu Mike , Gerhart John , Lowe Christopher J. 
Published: January 2023

AbstractHemichordates are an important group for investigating the evolution of bilaterian nervous systems. As the closest chordate outgroup with a bilaterally symmetric adult body plan, hemichordates are particularly informative for exploring the origins of chordates. Despite the importance of hemichordate neuroanatomy for testing hypotheses on deuterostome and chordate evolution, adult hemichordate nervous systems have not been comprehensively described using molecular techniques, and classic histological descriptions disagree on basic aspects of nervous system organization. A molecular description of hemichordate nervous system organization is important for both anatomical comparisons across phyla and for attempts to understand how conserved gene regulatory programs for ectodermal patterning relate to morphological evolution in deep time. Here, we describe the basic organization of the adult hemichordateSaccoglossus kowalevskiinervous system using immunofluorescence,in situhybridization, and transgenic reporters to visualize neurons, neuropil, and key neuronal cell types. Consistent with previous descriptions, we found theS. kowalevskiinervous system consists of a pervasive nerve plexus that is concentrated in the anterior, along with nerve cords on both the dorsal and ventral sides. Neuronal cell types exhibited clear anteroposterior and dorsoventral regionalization in multiple areas of the body. We observed spatially demarcated expression patterns for many genes involved in synthesis or transport of neurotransmitters and neuropeptides but did not observe clear distinctions between putatively centralized and decentralized portions of the nervous system. In the trunk, there is a clear division of cell types between the dorsal and ventral cords suggesting differences in function. The plexus shows regionalized structure and is consistent with the proboscis base as a major site for information processing rather than the dorsal nerve cord. The absence of neural processes crossing the basement membrane into muscle and extensive axonal varicosities suggest that volumetric transmission may play an important role in neural function. These data now facilitate more informed neural comparisons between hemichordates and other groups and contribute to broader debates on the origins and evolution of bilaterian nervous systems.
Composition of nasopharyngeal microbiota in individuals with SARS-CoV-2 infection across three COVID-19 waves in India
Authors: Bose Tungadri , Wasimuddin  , Acharya Varnali , Pinna Nishal Kumar , Kaur Harrisham , Ranjan Manish , Jandhyala SaiKrishna , Nagabandi Tulasi , Varma Binuja , Tallapaka Karthik Bharadwaj , Sowpati Divya Tej , Haque Mohammed Monzoorul , Dutta Anirban , Siva Archana Bharadwaj , Mande Sharmila S. 
Published: January 2023

AbstractMultiple variants of the SARS-CoV-2 virus have been plaguing the world through successive waves of infection over the past three years. Studies by independent research groups across geographies have shown that the microbiome composition in COVID-19 patients (CP) differ from that of healthy individuals (CN). However, such observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern. We also present the variations in microbiota of symptomatic vs asymptomatic COVID-19 patients. The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The generaStaphylococcus,Anhydrobacter,Thermus, andAerococcuswere observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection. To our knowledge, this is the first longitudinal study which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Such studies not only pave way for better understanding of the disease pathophysiology but also help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.
Rice potassium transporter OsHAK18 mediates phloem K+loading and redistribution
Authors: Shen Like , Wu Qi , Fan Wenxia , Luan Junxia , Li Na , Chen Di , Tian Quanxiang , Jing Wen , Zhang Wenhua 
Published: January 2023

ABSTRACTHigh-Affinity K+transporters/K+Uptake Permeases/K+Transporters (HAK/KUP/KT) are important pathways mediating K+transport across cell membrane, which function in maintaining K+homeostasis during plant growth and stress response. An increasing number of studies have shown that HAK/KUP/KT transporters play important roles in potassium uptake and root-to-shoot translocation. However, whether some HAK/KUP/KT transporters mediate K+redistribution in phloem remains unknown. In this study, we revealed that a phloem-localized HAK/KUP/KT transporter, OsHAK18 operated as a typical KUP/HAK/KT transporter mediating cell K+uptake when expressed in yeast,E. coliandArabidopsis. It was localized at plasma membrane. Disruption ofOsHAK18rendered rice seedlings insensitive to low-K+stress. Compared with WT, theoshak18mutants accumulated more K+in shoots but less K+in roots, leading to a higher shoot/root ratio of K+per plant. Although disruption ofOsHAK18doesn’t affect root K+uptake and K+level in xylem sap, it significantly decreases phloem K+concentration and inhibits root-to-shoot-to-root K+translocation in split-root assay. These results reveal that OsHAK18 mediates phloem K+loading and redistribution, whose disruption is favor of shoot K+retention under low-K+stress. Our findings not only reveal a unique function of rice HAK/KUP/KT family member, but also provide a promising strategy to improve rice tolerance under K+deficiency.
EZH2mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition
Authors: Romero Pierre , Richart Laia , Aflaki Setareh , Burton Megan , Michaud Audrey , Masliah-Planchon Julien , Kuhnowski Frédérique , Méaudre Céline , Luscan Armelle , Hamza Abderaouf , Legoix Patricia , Vincent-Salomon Anne , Wassef Michel , Holoch Daniel , Margueron Raphaël 
Published: January 2023

AbstractMutations in chromatin regulators or their histone substrates are widespread in cancer and often play decisive roles in tumorigenesis. These include Polycomb Repressive Complex 2 (PRC2), a histone H3 lysine 27 methyltransferase that shows distinct alterations in each of a range of tumor types. Mechanistically, this tumor-type specificity is poorly understood. Here, we model several of these alterations in a single isogenic system in order to reveal their comparative impacts on chromatin and transcription. Focusing then on gain-of-function substitutions in catalytic subunit EZH2, which occur in ∼25% of follicular lymphomas, we show thatEzh2Y641Finduces aberrant H3K27 methylation patterns even without wild-typeEzh2, and that these are alleviated by partial PRC2 inhibition.Ezh2Y641Falso causes gains in existing H3K27 acetylation peaks and extensive gene expression changes. Remarkably,Ezh2Y641Ftransforms the transcriptomic response to PRC2 inhibition, leading notably to the induction of antigen presentation genes in mutant cells. Using a unique longitudinal cohort of FL patient samples we further strengthen the link betweenEZH2mutation status and abnormal H3K27 methylation. This analysis also uncovered unexpected variability in the mutational landscape of successive biopsies from the same patient that points to the frequent co-existence of different clones. On a clinical level, this urges caution when stratifying patients based on single tumor sampling. Altogether, our results provide a mechanistic foundation for understanding how oncogenic PRC2 mutations disrupt chromatin and transcription, and the therapeutic vulnerabilities this creates.
MitoMouse is a model reconstruction of murine mitochondrial metabolism
Authors: Chapman Stephen P. , Molinié Thibaut , Mourier Arnaud , Habermann Bianca H. 
Published: January 2023

AbstractMitochondria, apart from being the powerhouses of our cells, are key players in cellular metabolism and homeostasis. As a consequence, the core bioenergetics and metabolism of mitochondria are well studied considering the role that dysregulated mitochondrial metabolism plays in disease. Flux Balance Analysis, used in conjunction with metabolic model reconstructions is a powerful computational tool that predicts metabolism. The resulting quantitative descriptions of metabolic dysregulation not only allows current hypotheses to be testedin silico, but can also lead to novel model driven hypotheses that can be experimentally verified. Several metabolic reconstructions for human and mouse metabolism exist, but no model specific to mouse mitochondrial metabolism exists. Here, we have created a mouse-specific mitochondrial metabolic model, mitoMouse, which is based on the high-quality human MitoCore mode. MitoMouse contains 390 genes and 445 metabolites involved in 560 unique reactions, is able to model central carbon metabolism and has been extended to contain reduction of the CoQ complex of Oxidative Phosphorylation by the enzyme DHODH. MitoMOuse was validated to accurately model the important metabolic switch involving CoQ reduction resulting from increased malate import, as recently shown in mouse cardiac tissue. We expect this model to be of immense interest and relevance to researchers working on murine mitochondrial metabolism.
Cognition’s dependence on functional network integrity with age is conditional on structural network integrity
Authors: Liu Xulin , Tyler Lorraine K ,   Cam-CAN, Davis Simon W , Rowe James B , Tsvetanov Kamen A 
Published: January 2023

AbstractMaintaining good cognitive function is crucial for well-being across the lifespan. We proposed that the degree of cognitive maintenance is determined by the functional interactions within and between large-scale brain networks. Such connectivity can be represented by the white matter architecture of structural brain networks that shape intrinsic neuronal activity into integrated and distributed functional networks. We explored how the function-structure connectivity convergence, and the divergence of functional connectivity from structural connectivity, contribute to the maintenance of cognitive function across the adult lifespan. Multivariate analyses were used to investigate the relationship between function-structure connectivity convergence and divergence with multivariate cognitive profiles, respectively. Cognitive function was increasingly dependent on function-structure connectivity convergence as age increased. The dependency of cognitive function on connectivity was particularly strong for high-order cortical networks and subcortical networks. The results suggest that brain functional network integrity sustains cognitive functions in old age, as a function of the integrity of the brain’s structural connectivity.
The Embryonic Origin of Primordial Germ Cells in the TardigradeHypsibius exemplaris
Authors: Heikes Kira L. , Game Mandy , Smith Frank W. , Goldstein Bob 
Published: January 2023

AbstractPrimordial germ cells (PGCs) give rise to gametes – cells necessary for the propagation and fertility of diverse organisms. Current understanding of PGC development is limited to the small number of organisms whose PGCs have been identified and studied. Expanding the field to include little-studied taxa and emerging model organisms is important to understand the full breadth of the evolution of PGC development. In the phylum Tardigrada, no early cell lineages have been identified to date using molecular markers. This includes the PGC lineage. Here, we describe PGC development in the model tardigradeHypsibius exemplaris. The four earliest-internalizing cells (EICs) exhibit PGC-like behavior and nuclear morphology. The location of the EICs is enriched for mRNAs of conserved PGC markerswiwi1(water bearpiwi1) andvasa. At early stages, bothwiwi1andvasamRNAs are detectable uniformly in embryos, which suggests that these mRNAs do not serve as localized determinants for PGC specification. Only later arewiwi1andvasaenriched in the EICs. Finally, we traced the cells that give rise to the four PGCs. Our results reveal the embryonic origin of the PGCs ofH. exemplarisand provide the first molecular characterization of an early cell lineage in the tardigrade phylum. We anticipate that these observations will serve as a basis for characterizing the mechanisms of PGC development in this animal.
Gre factors protect against phenotypic diversification and cheating inEscherichia colipopulations under toxic metabolite stress
Authors: Sivaloganathan Darshan M. , Wan Xuanqing , Brynildsen Mark P. 
Published: January 2023

AbstractNitric oxide (·NO) is one of the toxic metabolites that bacteria can be exposed to within phagosomes. Gre factors, which are also known as transcript cleavage factors or transcription elongation factors, relieve back-tracked transcription elongation complexes by cleaving nascent RNAs, which allows transcription to resume after stalling. Here we discovered that loss of both Gre factors inE. coli, GreA and GreB, significantly compromised ·NO detoxification through a phenotypic diversification of the population. Under normal culturing conditions, both wild-type and ΔgreAΔgreBsynthesized protein uniformly. However, treatment with ·NO led to bimodal protein expression in ΔgreAΔgreB, whereas wild-type remained unimodal. Interestingly, exposure to another toxic metabolite of phagosomes, hydrogen peroxide (H2O2), produced similar results. We found that the diversification in ΔgreAΔgreBcultures requiredE. coliRNAP, occurred at the level of transcription, and could produce cheating where transcriptionally-deficient cells benefit from the detoxification activities of the transcriptionally-proficient subpopulation. Collectively, these results indicate that Gre factors bolster bacterial defenses by preventing phenotypic diversification and cheating in environments with fast-diffusing toxic metabolites.ImportanceToxic metabolite stress occurs in a broad range of contexts that are important to human health, microbial ecology, and biotechnology; whereas Gre factors are highly conserved throughout the bacterial kingdom. Here we discovered that the Gre factors ofE. coliprevent phenotypic diversification under toxic metabolite stress. Such conformist regulation improves populationwide removal of those stressors and protects against cheating, where one subpopulation commits resources to counter a threat, and the other subpopulation does not, yet both subpopulations benefit.
MASH Native: A Unified Solution for Native Top-Down Proteomics Data Processing
Authors: Larson Eli J. , Pergande Melissa R. , Moss Michelle E. , Rossler Kalina J. , Wenger R. Kent , Krichel Boris , Josyer Harini , Melby Jake A. , Roberts David S. , Pike Kyndalanne , Shi Zhuoxin , Chan Hsin-Ju , Knight Bridget , Rogers Holden T. , Brown Kyle A. , Ong Irene M. , Jeong Kyowon , Marty Michael , McIlwain Sean J. , Ge Ying 
Published: January 2023

AbstractNative top-down proteomics (nTDP) integrates native mass spectrometry (nMS) with top-down proteomics (TDP) to provide comprehensive analysis of protein complexes together with proteoform identification and characterization. Despite significant advances in nMS and TDP software developments, a unified and user-friendly software package for analysis of nTDP data remains lacking. Herein, we have developed MASH Native to provide a unified solution for nTDP to process complex datasets with database searching capabilities in a user-friendly interface. MASH Native supports various data formats and incorporates multiple options for deconvolution, database searching, and spectral summing to provide a one-stop shop for characterizing both native protein complexes and proteoforms. The MASH Native app, video tutorials, written tutorials and additional documentation are freely available for download athttps://labs.wisc.edu/gelab/MASH_Explorer/MASHNativeSoftware.php. All data files shown in user tutorials are included with the MASH Native software in the download .zip file.
A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals non-hierarchical model of development
Authors: Lee Julie , Møller Andreas Fønss , Chae Shinhyeok , Bussek Alexandra , Park Tae Joo , Kim Youni , Lee Hyun-Shik , Pers Tune H. , Kwon Taejoon , Sedzinski Jakub , Natarajan Kedar Nath 
Published: January 2023

AbstractThe specialized cell-types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell-fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developingXenopusMCE from pluripotent to mature stages by single-cell transcriptomics, identifying novel, multipotentearly epithelial progenitorsthat execute multi-lineage cues before specialising into late-stage ionocytes, goblet and basal cells. Combiningin silicolineage inference,in situhybridization and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors, chart cell- type emergence and fate progression into specialized cell-types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programmes across vertebrates. We uncover a continuous non-hierarchical model of MCE development alongside a significant data resource for understanding respiratory biology.