bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hijacked Immune Cells Traverse Microenvironmental Barriers by Positioning and Pushing their Intracellular Parasite Cargo
Authors: Ruiz-Fernandez Mauricio J.A. , Jiang Jianfei , Mortazavi Armina , Wang Bingzhi , Kuznetcov Artur , Merrin Jack , Meissner Markus , Periz Javier , Sabass Benedikt , Renkawitz Jörg 
Published: May 2024

AbstractIntracellular pathogens hijack the cytoskeletal networks of their host cells to facilitate their uptake, drive their intracellular motility, or prevent their degradation. While many underlying principles have been explored during host cell infections by intracellular bacteria likeListeria, Chlamydia, orShigella, it remains less well understood how large eukaryotic intracellular parasites likeToxoplasma gondiiexploit the host cytoskeleton. In particular, howToxoplasmaachieves its transport within highly motile immune cells remains largely unknown despite its large intracellular size. Here, we discover thatToxoplasma gondiihijacks host myosin forces for translocation through microenvironmental barriers along immune cell migration paths. Using highly defined micro-engineered migration paths and dendritic cells as a highly motile immune cell model, we reveal that large parasitic cargos acquire a surprising intracellular position frontward of the host nucleus and microtubule-organizing center. This frontward localization of parasitic cargos depends on microenvironmental confinement and host myosin activity. We identify that the parasite cargos cause high contractility within their motile host cells mediated by host myosin-II, thereby facilitating their squeezing and deformation to enable transversal through confining microenvironments. Our findings establish parasitic hijacking of myosin forces as a novel principle of how parasites exploit host cytoskeletal networks.
Lcn2 protects from cisplatin induced AKI by regulating DNA damage response via EGFR activation
Authors: Zablocki Aniela , Marques Eloise , Yammine Lucie , Nguyen Clément , Terzi Fabiola , Gallazzini Morgan 
Published: May 2024

SUMMARYBackgroundLipocalin 2 (Lcn2), a small-secreted protein, is an established sensitive biomarker of kidney injury. In Cisplatin (CDDP) induced acute kidney injury (AKI), Lcn2 expression is swiftly and strongly increased in suffering renal medullary tubules. While recent reports correlates Lcn2 expression in cancer cells with CDDP resistance, the role of Lcn2 in kidney tubule damaged by CDDP remains unknown.MethodsTo better understand the role of Lcn2 in CDDP-induced AKI, experiments onLcn2+/+orLcn2−/−mice as well as immortalized kidney cells knock-down (KD) for Lcn2 were conducted. Kidney function and injury were assessed using standard techniques. Cellular and molecular mechanisms were studied in WT and Lcn2 KD cells in combination with pathways inhibitors in order to gain insight Lcn2 driven mechanisms.ResultsIn animal injected with CDDP, Lcn2 was upregulated mostly in kidney inner medulla collecting duct while it was reabsorbed in the proximal tubules.Lcn2−/−in mice significantly decreased kidney function compare to WT mice, while it increased parenchymal damage due to increased cell death and cast formation. Interestingly, while little to no damage were present in the medulla of CDDP injected WT animal, a clear increase of medulla tubular lesions was observed inLcn2−/−mice. Using Inner Medullary Collecting Duct cells (mIMDC-3), we showed that Lcn2 KD induces a p53-dependent apoptosis upon Cisplatin exposure while no effect on necrosis was observed. Finally, we demonstrated that Lcn2 drives CDDP resistance to apoptosis through the activation of the pro-survival EGFR pathway.ConclusionsWe established that Lcn2 is a renoprotective protein in CDDP-induced AKI via the activation of EGFR pathway. This new mechanism might represent a new approach for the treatment of AKI.
Directed evolution for cell separation in budding yeast
Authors: Galeota-Sprung Benjamin , Pritchard Erik , Huang Crystal , Fernandez Amy , Sniegowski Paul 
Published: May 2024

AbstractHaploid and diploid natural isolates of the yeastSaccharomyces cerevisiaewere evolved under a daily transfer protocol that selected against clumpy growth and for cell separation. For the haploid populations, whole genome sequencing revealed strong selection to deactivateAMN1, a known regulator of cell separation, recapitulating evolution that likely occurred during the domestication of common lab strains. We also observed multiple mutational hits to the Rim101 pathway, which was not expected. Mutations to bothAMN1and the Rim101 pathway were strongly associated with cell separation. In the diploid populations, we observed the parallel emergence of a large partial deletion of chrIII, the so-called Hawthorn’s deletion. We show that this deletion is associated with reduced clumpy growth. The mechanism by which Hawthorne’s deletion affects cell separation is unknown but may be related to an effect on budding pattern.
CodY controls the SaeR/S two-component system by modulating branched-chain fatty acid synthesis inStaphylococcus aureus
Authors: Alqahtani Shahad , DiMaggio Dennis A. , Brinsmade Shaun R 
Published: May 2024

AbstractStaphylococcus aureusis a Gram-positive, opportunistic human pathogen that is a leading cause of skin and soft tissue infections and invasive disease worldwide. Virulence in this bacterium is tightly controlled by a network of regulatory factors. One such factor is the global regulatory protein CodY. CodY links branched-chain amino acid sufficiency to the production of surface-associated and secreted factors that facilitate immune evasion and subversion. Our previous work revealed that CodY regulates virulence factor gene expression indirectly in part by controlling the activity of the SaeRS two-component system. While this is correlated with an increase in membrane anteiso-15:0 and −17:0 branched-chain fatty acids (BCFAs) derived from isoleucine, the true mechanism of control has remained elusive. Herein, we report that CodY-dependent regulation of SaeS sensor kinase activity requires BCFA synthesis. During periods of nutrient sufficiency, BCFA synthesis and Sae TCS activity is heavily suppressed by CodY-dependent repression of theilv-leuoperon and the isoleucine-specific permease genebrnQ2.In acodYnull mutant, which simulates extreme nutrient limitation, de-repression ofilv-leuandbrnQ2directs the synthesis of enzymes in redundant de novo and import pathways to catalyze the production of BCFA precursors. Overexpression ofbrnQ2independent of CodY is sufficient to increase membrane anteiso BCFAs, Sae-dependent promoter activity, and SaeR∼P levels. Our results further clarify the molecular mechanism by which CodY controls virulence inS. aureus.IMPORTANCEExpression of bacterial virulence genes often correlates with the exhaustion of nutrients, but how the signaling of nutrient availability and the resulting physiological responses are coordinated is unclear. InS. aureus,CodY controls the activity of two major regulators of virulence – the Agr and Sae two-component systems – by unknown mechanisms. This work identifies a mechanism by which CodY controls the activity of the sensor kinase SaeS by modulating the flux of anteiso branched-chain amino acids to the membrane. Understanding the mechanism adds to our understanding of how bacterial physiology and metabolism are linked to virulence and underscores the homeostatic nature of virulence. Understanding the mechanism also opens potential avenues for targeted therapeutic strategies againstS. aureusinfections.
Mycelium as a scaffold for biomineralized engineered living materials
Authors: Viles Ethan , Heyneman Ethan , Lin Shuyi , Montague Virginia , Darabi Amir , Cox Lewis M. , Phillips Adrienne , Gerlach Robin , Espinosa-Ortiz Erika , Heveran Chelsea 
Published: May 2024

SummaryEngineered living materials (ELMs) are garnering considerable attention as a promising alternative to traditional building materials because of their potentially lower carbon footprint and additional functionalities conferred by living cells. However, biomineralized ELMs designed for load-bearing purposes are limited in their current design and usage for several reasons, including (1) low microbial viability and (2) limited control of specimen internal microarchitecture. We created ‘third generation’ biomineralized ELMs from fungal mycelium scaffolds that were mineralized either by the fungus itself or by ureolytic bacteria. Both self-mineralized (i.e. fungally-mineralized) and bacterially-mineralized scaffolds retained high microbial viability for at least four weeks in room temperature or accelerated dehydration storage conditions, without the addition of protectants against desiccation. The microscale modulus of calcium carbonate varied with the different biomineralized scaffold conditions, and moduli were largest and stiffest for bacterial biomineralization of fungal mycelium. As an example of how mycelium scaffolds can enable the design of complex internal geometries of biomineralized materials, osteonal-bone mimetic architectures were patterned from mycelium and mineralized using ureolytic bacteria. These results demonstrate the potential for mycelium scaffolds to enable new frontiers in the design of biomineralized ELMs with improved viability and structural complexity.Progress and PotentialBiomineralized engineered living materials (ELMs) offer new approaches for increasing the sustainability of building materials and processes. However, the design and usage of biomineralized ELMs is constrained by several important limitations, including low microbial viability and limited ability to control internal microarchitecture. Fungal mycelium scaffolds, biomineralized by either fungi or bacteria, achieve much higher viability of ureolytic microorganisms than what has been reported for biomineralized ELMs. Further, mycelium scaffolds permit the manufacturing of complex architectures, such as inspired by the structure of osteonal bone. Mycelium scaffolds have the potential to enable new frontiers in the design and use of biomineralized ELMs.Graphical Abstract
Bisphenol A affects the development and the onset of photosymbiosis in the acoelSymsagittifera roscoffensis
Authors: Pennati R. , Cartelli N. , Castelletti C. , Ficetola F. , Bailly X. , Mercurio S. 
Published: May 2024

AbstractPhotosymbiosis indicates a long-term association between animals and photosynthetic organisms. It has been mainly investigated in photosymbiotic cnidarians, while other photosymbiotic associations have been largely neglected. The acoelSymsagittifera roscoffensislives in obligatory symbiosis with the microalgalTetraselmis convolutaeand has recently emerged as alternative model to study photosymbiosis. Here, we investigated the effects of Bisphenol A, a common plastic additive, on two pivotal stages of its lifecycle: aposymbiotic juvenile development and photosymbiogenesis. Based on our results, this pollutant altered the development of the worms and their capacity to engulf algae from the environment at concentrations higher than the levels detected in seawater, yet aligning with those documented in sediments of populated areas. Data provide novel information about the effects of pollutants on photosymbiotic associations and prompt the necessity to monitor their concentrations in marine environmental matrices.
Optimal antimicrobial dosing combinations when drug-resistance mutation rates differ
Authors: Delaney Oscar , Letten Andrew D. , Engelstädter Jan 
Published: May 2024

AbstractGiven the ongoing antimicrobial resistance crisis, it is imperative to develop dosing regimens optimised for avoiding the evolution of resistance. The rate at which bacteria acquire resistance-conferring mutations to different antimicrobial drugs spans multiple orders of magnitude. By using a mathematical model and computer simulations, we show that knowledge of relative mutation rates can meaningfully inform the optimal combination of two drugs in a treatment regimen. We demonstrate that under plausible assumptions there is a linear relationship in log-log space between the drugA:drugBdose ratio that maximises the chance of treatment success and the ratio of their mutation rates. This power law relationship holds for bacteriostatic and bactericidal drugs. If borne out empirically, these findings suggest there might be significant room to further optimise antimicrobial dosing strategies.
The CcpNmr Analysis Simulated Metabolomics Database (CASMDB): An Open-Source Collection of Metabolite Annotation Data for 1D1H NMR-Based Metabolomics
Authors: Hayward Morgan W. , Mureddu Luca G. , Thompson Gary , Phelan Marie , Brooksbank Edward J. , Vuister Geerten W. 
Published: May 2024

AbstractDatabases are invaluable for the identification of individual metabolites in untargeted metabolomics analyses, providing annotated pure metabolite references that allow for comparisons with experimentally collected mixture samples. Despite the value of an extensive reference database, publicly available databases for NMR-based metabolomics are often incomplete with respect to experimental conditions and derived NMR annotation parameters, such as peak positions. Hence, they are not designed for visualising the reference spectra alongside an experimental sample spectrum of interest, thus limiting the usefulness of the database. As a consequence, researchers have resorted to their own user- or application based database implementations.In this paper we describe the collection, remediation and integration of annotation data from the publicly available HMDB, BRMB and GISMO NMR metabolomics databases to build the CcpNmr Analysis Simulated Metabolomics Database (CASMDB) that contains 1932 unique metabolite entries. This database, in concert with the AnalysisMetabolomics programme, also allows or accurate simulation of spectra at arbitrary field strengths. Together, these tools underpin the visualising of experimental and simulated metabolite references and their usage in 1D1H NMR-based metabolomics studies.
Serotonin attenuates tumor-necrosis-factor-alpha-induced intestinal inflammation by interacting with human mucosal tissue
Authors: Bosáková Veronika , Papatheodorou Ioanna , Kafka Filip , Tomášiková Zuzana , Hortová Kohoutková Marcela , Frič Jan 
Published: May 2024

AbstractThe intestine houses the largest reservoir of immune cells and is serviced by the largest and most complex peripheral nervous system in the human body. The gut-brain axis orchestrates bidirectional communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Using a human 3Din vitromodel, we investigated the effect of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Our findings revealed that serotonin attenuates the tumor-necrosis-factor-alpha-induced pro-inflammatory response, mostly by affecting the expression of chemokines. Serotonin was found to impact tissue-migrating monocytes’ phenotype and distribution, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, using fully human 3D model of intestine, our results show for the first time that serotonin has a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of intestinal inflammation.In vivostudies focused on role of neuromodulators in gut homeostasis and inflammation have shown controversial results, highlighting importance of development of human experimental models. Moreover, our results emphasize importance of human health research in human-cell-based models and suggests serotonin signaling pathway as new potential therapeutic target for inflammatory bowel disease patients.
Alcohol-induced sleep dysregulation in Drosophila is dependent on the neuropeptide PDF
Authors: Ramirez-Roman Maria E. , Fuenzalida-Uribe Nicolás L. , Ayala-Santiago Genesis , Agosto Jose L. , Ghezzi Alfredo 
Published: May 2024

AbstractAlcohol exposure is known to trigger homeostatic adaptations in the brain that lead to the development of tolerance and dependence. These adaptations are also believed to be the root of a series of disturbances in sleep patterns that often manifest during the development of alcoholism and can have significant clinical and economic consequences. Unfortunately, the neuronal and genetic pathways that control the effects of alcohol on sleep are currently unknown, thus limiting our efforts to find effective treatment. In this study, we conduct a mechanistic exploration of the relationships between alcohol and sleep alterations using aDrosophilamodel system. We show that the genetic manipulation of the ventral lateral neurons (LNv) —a set of neurons known to control sleep inDrosophila— disrupts alcohol sensitivity and tolerance. Moreover, we show that alcohol exposure induces a series of alterations in sleep patterns that last for several days. Our results demonstrate that a single alcohol exposure promotes daytime sleep, alters the structure of sleep during the night, and reduces morning anticipatory behavior. In addition, we show that some of these alterations partially depend on the activity of the neuropeptide PDF, a key element in regulating sleep architecture. We propose that alcohol-induced sleep disruption stems from alterations in the activity of the PDF-releasing LNv neurons and that these alterations are similar to those that produce alcohol tolerance.
Clearing method adapted to FFPE tissues for 3D imaging of nerve fibers, B cells, and tertiary lymphoid structures
Authors: Azar Safa , Letaïef Laïla , Malkinson Guy , Martin Sabrina , Validire Pierre , Teillaud Jean-Luc , Dieu-Nosjean Marie-Caroline , Brunet Isabelle 
Published: May 2024

SummaryBiomedical samples are commonly used for histological examination after their inclusion in paraffin (Formalin-Fixed Paraffin-Embedded (FFPE) biopsy). However, they provide minimal information about the interactions between different tissue components such as blood vessels, nerves, and cellular aggregates. Here we present a modified iDISCO tissue-clearing method that we term miDISCO+. miDISCO+can be used for analyzing FFPE samples, requires the use of only one single FFPE sample, and allows to acquire a detailed image of the 3D tissue/organ architecture and the relevant cellular interactions. The addition of an antigen retrieval step to the protocol enables to use antibodies whose binding is sensitive to formalin fixation due to antigen masking. This method enabled us to detect CD20+B cell follicles and to show that they are in close contact with TH+sympathetic nerve fibers in FFPE biopsies of human palatine tonsils, and to detect CD20+B cells in lung tumors and observe their 3D organization within tertiary lymphoid structures. Thus, miDISCO+could be a potent tool for clinicians to refine diagnosis and to select optimal personalized treatment by giving an integrated 3D view of the tissue structures and cellular interactions in single FFPE samples.
WITHDRAWN: Molecular Insights into Zea mays Active Phytochemicals for Diabetes and Inflammation Treatment: A Web App-Based Machine Learning and Network Pharmacology Approach
Authors: Manaithiya Ajay , Bhowmik Ratul , Elhenawy Ahmed A. , Sharma Sameer , Dinesh Susha , Parkkila Seppo , Aspatwar Ashok 
Published: May 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to the inability to complete the revisions or follow up on the manuscript at this time, due to personal circumstances. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Theory of electron spin resonance in scanning tunneling microscopy
Authors: Ast Christian R. , Kot Piotr , Ismail Maneesha , de-la-Peña Sebastián , Fernández-Domínguez Antonio I. , Cuevas Juan Carlos 
Published: May 2024

Electron spin resonance (ESR) spectroscopy in scanning tunneling microscopy (STM) has enabled probing the electronic structure of single magnetic atoms and molecules on surfaces with unprecedented energy resolution, as well as demonstrating coherent manipulation of single spins. Despite this remarkable success, the field could still be greatly advanced by a more quantitative understanding of the ESR-STM physical mechanisms. Here, we present a theory of ESR-STM that quantitatively models not only the ESR signal itself, but also the full background tunneling current, from which the ESR signal is derived. Our theory is based on a combination of Green's function techniques to describe the electron tunneling and a quantum master equation for the dynamics of the spin system along with microwave radiation interacting with both the tunneling current and the magnetic system. We show that this theory is able to quantitatively reproduce the experimental results for a spin-1/2 system (TiH molecules on MgO) across many orders of magnitude in tunneling current, providing access to the relaxation and decoherence rates that govern the spin dynamics due to intrinsic mechanisms and to the applied bias voltage. More importantly, our work establishes that (i) sizable ESR signals, which are a measure of microwave-induced changes in the junction magnetoresistance, require surprisingly high tip spin polarizations, and (ii) the coupling of the magnetization dynamics to the microwave field gives rise to the asymmetric ESR spectra often observed in this spectroscopy. Additionally, our theory provides very specific predictions for the dependence of the relaxation and decoherence times on the bias voltage and the tip-sample distance. Finally, with the help of electromagnetic simulations, we find that the transitions in our ESR-STM experiments, in which the tunnel junction is irradiated by a nearby microwave antenna, can be driven by the ac magnetic field at the junction.

Published by the American Physical Society
2024
Prospects for thermalization of microwave-shielded ultracold molecules
Authors: Wang Reuben R. W. , Bohn John L. 
Published: May 2024

Toward more efficient schemes for achieving deeply degenerate molecular Fermi gases, we study anisotropic thermalization in dilute gases of microwave shielded polar molecular fermions. For collision energies above the threshold regime, we find that thermalization is suppressed due to a strong preference for forward scattering and a reduction in total cross section with energy, significantly reducing the efficiency of evaporative cooling. We perform close-coupling calculations on the effective potential energy surface derived by Deng [] to obtain accurate two-body elastic differential cross sections across a range of collision energies. We use Gaussian process regression to obtain a global representation of the differential cross section over a wide range of collision angles and energies. The route to equilibrium is then analyzed with cross-dimensional rethermalization experiments, quantified by a measure of collisional efficiency toward achieving thermalization.

Published by the American Physical Society
2024