bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Drug Delivery with Supramolecular Amphiphilic Macrocycle Nanoparticles: Selective Targeting of CDK4/6 Inhibitor Palbociclib to Melanoma
Authors: Attia Mohamed F. , Ogunnaike Edikan A. , Pitz Megan , Elbaz Nancy M. , Panda Dillip K. , Alexander-Bryant Angela , Saha Sourav , Whitehead Daniel C. , Kabanov Alexander 
Published: November 2023

AbstractDrug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages,human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surface by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.Graphical abstract
Quantifying similarities between MediaPipe and a known standard for tracking 2D hand trajectories
Authors: Wagh Vaidehi P. , Scott Matthew W. , Kraeutner Sarah N. 
Published: November 2023

AbstractMarker-less motion tracking methods have promise for use in a range of domains, including clinical settings where traditional marker-based systems for human pose estimation is not feasible. MediaPipe is an artificial intelligence-based system that offers a markerless, lightweight approach to motion capture, and encompasses MediaPipe Hands, for recognition of hand landmarks. However, the accuracy of MediaPipe for tracking fine upper limb movements involving the hand has not been explored. Here we aimed to evaluate 2-dimensional accuracy of MediaPipe against a known standard. Participants (N = 10) performed trials in blocks of a touchscreen-based shape-tracing task. Each trial was simultaneously captured by a video camera. Trajectories for each trial were extracted from the touchscreen and compared to those predicted by MediaPipe. Specifically, following re-sampling, normalization, and Procrustes transformations, root mean squared error (RMSE; primary outcome measure) was calculated for coordinates generated by MediaPipe vs. the touchscreen computer. Resultant mean RMSE was 0.28 +/-0.064 normalized px. Equivalence testing revealed that accuracy differed between MediaPipe and the touchscreen, but that the true difference was between 0-0.30 normalized px (t(114) = -3.02,p= 0.002). Overall, we quantify similarities between MediaPipe and a known standard for tracking fine upper limb movements, informing applications of MediaPipe in a domains such as clinical and research settings. Future work should address accuracy in 3-dimensions to further validate the use of MediaPipe in such domains.
Chemical cues from beetle larvae trigger proliferation and putative virulence gene expression of a plant pathogen
Authors: Cambon Marine C. , Thomas Gareth , Caulfield John , Crampton Michael , Reed Katy , Doonan James M. , Hussain Usman , Denman Sandra , Vuts Jozsef , McDonald James E. 
Published: November 2023

AbstractAgricultural crop productivity and global forest biomes are coming under increasing threat from insect pests and microbial pathogens. This impact is worsened by inter- kingdom insect-microbe interactions that can increase transmission and disease severity in affected plants. Whilst bacterial chemical cues have been shown to directly influence insect behaviour, the impact of insect-derived compounds on phytopathogens is poorly understood. Here, we investigated the chemical basis for interactions between beetle larvae and bacteria in acute oak decline (AOD), a disease characterised by inner bark necrosis and involving a polymicrobial consortium includingBrenneria goodwiniiand larval galleries ofAgrilus biguttatus. We found thatA. biguttatuslarval extracts contain chemical elicitors that increase bacterial growth rate and final cell density duringin vitroculture, and stimulate the differential expression of ∼600 genes, including the Type III Secretion System and its effectors, which are major virulence factors in plant pathogens. Chemical compounds from closely related insect species did not have this effect. These findings highlight the importance of inter-kingdom interactions in plant disease and suggests a novel mode-of-action for insect-derived chemical elicitors in facilitating the virulence of phytopathogens.
Constraining activity and growth substrate of fungal decomposers via assimilation patterns of inorganic carbon and water into lipid biomarkers
Authors: Jabinski Stanislav , Rangel Wesley d.M. , Kopáček Marek , Jílková Veronika , Jansa Jan , Meador Travis B. 
Published: November 2023

AbstractFungi are among the few organisms on the planet that can metabolize recalcitrant C but are also known to access recently produced plant photosynthate. Therefore, improved quantification of growth and substrate utilization by different fungal ecotypes will help to define the rates and controls of fungal production, the cycling of soil organic matter, and thus the C storage and CO2buffering capacity soil ecosystems. This study combined a dual stable isotope probing approach together with rapid analysis by tandem pyrolysis gas chromatography isotope ratio mass spectrometry (Pyr-GC-IRMS) to determine the patterns of water-derived hydrogen (H) and inorganic C assimilated into lipid biomarkers of heterotrophic fungi as a function of C substrate. The water H assimilation factor (αw) and the inorganic C assimilation for C18:2fatty acid isolated from five fungal species growing on glucose was lower (0.62±0.01 and 4.7±1.6%, respectively) than for species grown on glutamic acid (0.90±0.02 and 7.4±3.7%, respectively). Furthermore, the assimilation ratio (RIC/αW) for growth on glucose and glutamic acid can distinguish between these two metabolic modes. This dual SIP assay thus delivers estimates of fungal activity and may help to delineate the predominant substrates that are respired among a matrix of compounds found in natural environments. (200 Words)ImportanceFungi decomposers play important roles in food webs and nutrient cycling because they can feed on both labile and stable forms of carbon. This study developed and applied a dual stable isotope assay to improve the investigation of fungal activity in the environment. By determining the incorporation patterns of hydrogen and carbon into fungal lipids, this assay delivers estimates of fungal activity and the different metabolic pathways that they employ in ecological and environmental systems. (75 Words)
Outer membrane vesicles from commensal and pathogenic anaerobic bacteria: a systematic review of literature reviews
Authors: Castro-Vargas Priscilla , Barloy-Hubler Frédérique , Acuña-Amador Luis 
Published: November 2023

AbstractOuter membrane vesicles (OMVs) are constitutively produced by Gram-negative bacteria (GNB), those from pathogenic bacteria play key roles in pathogen-host interactions, modulating host’s immune response and promoting virulence. OMVs of commensal bacteria are fundamental in the maturation of the host immune system and to maintain intestinal homeostasis.The objective of this systematic review was to synthesize the knowledge available on literature reviews on OMVs from anaerobic GNB. The information was classified into categories: induction and biogenesis, OMVs liberation, internalization by host cells, and their interaction. The most studied OMVs are fromPorphyromonas gingivalisandBacteroidesspp.
THER: Integrative Web Tool for Tumor Hypoxia Exploration and Research
Authors: Zhang Yasi , Lin Anqi , Yang Hong , Liu Zaoqu , Cheng Quan , Zhang Jian , Luo Peng 
Published: November 2023

AbstractHypoxia is an important factor in the adaptation of tumor cells to their environment, contributes to their malignant progression, and affects tumor prognosis and drug sensitivity. Although there is a wealth of transcriptomic data stored in public databases, there is a lack of web-based tools for analyzing these data to explore the link between hypoxia and the mechanisms of tumorigenesis and progression. To this end, we have developed an interactive web-based tool called THER, which is designed to help users easily identify potential targets, mechanisms of action and effective drugs for treating hypoxic tumors. THER integrates 63 transcriptomic tumor hypoxia datasets from the Gene Expression Omnibus (GEO) database, covering 3 species, 18 tumor types and 42 cell line types. This web tool provides five modules that allow users to perform differential expression analysis, expression profiling analysis, correlation analysis, enrichment analysis and drug sensitivity analysis on different datasets based on different oxygen statuses. We expect that users will be able to use the tool to identify valuable biomarkers, further reveal the molecular mechanisms of tumor hypoxia, and identify effective drugs, thus providing a scientific basis for tumor diagnosis and treatment. THER is open to all users and can be accessed without login athttps://smuonco.shinyapps.io/THER/.
Baseline malaria infection status and RTS,S/AS01E malaria vaccine efficacy
Authors: Juraska Michal , Early Angela M. , Li Li , Schaffner Stephen F. , Lievens Marc , Khorgade Akanksha , Simpkins Brian , Hejazi Nima S. , Benkeser David A. , Wang Qi , Mercer Laina D. , Adjei Samuel , Agbenyega Tsiri , Anderson Scott , Ansong Daniel , Bii Dennis K. , Buabeng Patrick B.Y. , English Sean , Fitzgerald Nicholas , Grimsby Jonna , Kariuki Simon K. , Otieno Kephas , Roman François , Samuels Aaron M. , Westercamp Nelli , Ockenhouse Christian F. , Ofori-Anyinam Opokua , Lee Cynthia K. , MacInnis Bronwyn L. , Wirth Dyann F. , Gilbert Peter B. , Neafsey Daniel E. 
Published: November 2023

AbstractBackgroundThe only licensed malaria vaccine, RTS,S/AS01E, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy (VE).Methods1,500 children aged 5–17 months were randomized to receive four different RTS,S/AS01Eregimens or a rabies control vaccine in a phase 2b clinical trial in Ghana and Kenya. We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods in over 36K participant specimens. We performed a post hoc analysis of VE based on malaria infection status at first vaccination and force of infection.ResultsWe observed significant and comparable VE (25–43%, 95% CI union 9–53%) against first new infection for all four RTS,S/AS01Eregimens across both follow-up periods (12 and 20 months). Each RTS,S/AS01Eregimen significantly reduced the number of new infections in the 20-month follow-up period (control mean 4.1 vs. RTS,S/AS01Emean 2.6–3.0). VE against first new infection was significantly higher in participants who were malaria-infected (68%; 95% CI, 50 to 80%) versus uninfected (37%; 95% CI, 23 to 48%) at the first vaccination (P=0.0053) and in participants experiencing greater force of infection between dose 1 and 3 (P=0.059).ConclusionsAll tested dosing regimens blocked some infections to a similar degree. Improved VE in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation. (ClinicalTrials.govnumber,NCT03276962)
INFLUENCE OF BACILLUS SUBTILIS ON THE BIOTOXICITY OF SOILS CONTAMINATED WITH COPPER
Authors: Galaktionova L.V. 
Published: November 2023

AbstractAn urgent environmental problem is pollution of the environment with heavy metals, which have a negative impact on the components of ecosystems. Therefore, the search for new approaches to reduce their toxicity/availability in soil is a task of applied research. This work studied the effect of inoculation with bacteriaBacillus subtilis534 of contaminated soils with copper acetates on their toxicity to higher plants, earthworms, and bacteria of the genusAzotobacter.
Transwell-based microphysiological platform for high-resolution imaging of airway tissues
Authors: Kurmashev Amanzhol , Boos Julia A. , Laventie Benoît-Joseph , Swart A. Leoni , Sütterlin Rosmarie , Junne Tina , Jenal Urs , Hierlemann Andreas 
Published: November 2023

AbstractTranswell-based airway models have become increasingly important to study the effects of respiratory diseases and drug treatment at the air-liquid interface of the lung epithelial barrier. However, the underlying mechanisms at tissue and cell level often remain unclear, as transwell inserts feature limited live-cell imaging compatibility. Here, we report on a novel microphysiological platform for the cultivation of transwell-based lung tissues providing the possibility to alternate between air-liquid and liquid-liquid interfaces. While the air-liquid interface recapitulates physiological conditions for the lung model, the liquid-liquid interface enables live-imaging of the tissue at high spatiotemporal resolution. The plastics-based microfluidic platform enables insertion and recuperation of the transwell inserts, which allows for tissue cultivation and analysis under standardized well plate conditions. We used the device to monitor infections ofPseudomonas aeruginosain human stem-cell-derived bronchial epithelial tissue. We continuously imaged the progression of aP. aeruginosainfection in real time at high resolution, which provided insights into bacterial spreading and invasion on the apical tissue surface, as well as insights into tissue breaching and destruction over time. The airway tissue culture system is a powerful tool to visualize and elucidate key processes of developing respiratory diseases and to facilitate drug testing and development.
Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates
Authors: Moliva Juan I. , Andrew Shayne F. , Flynn Barbara J. , Wagner Danielle A. , Foulds Kathryn E. , Gagne Matthew , Flebbe Dillon R. , Lamb Evan , Provost Samantha , Marquez Josue , Mychalowych Anna , Lorag Cynthia G. , Honeycutt Christopher Cole , Burnett Matthew R. , McCormick Lauren , Henry Amy R. , Godbole Sucheta , Davis-Gardner Meredith E. , Minai Mahnaz , Bock Kevin W. , Nagata Bianca M. , Todd John-Paul M. , McCarthy Elizabeth , Dodson Alan , Kouneski Katelyn , Cook Anthony , Pessaint Laurent , Van Ry Alex , Valentin Daniel , Young Steve , Littman Yoav , Boon Adrianus C. M. , Suthar Mehul S. , Lewis Mark G. , Andersen Hanne , Alves Derron A. , Woodward Ruth , Leuzzi Adriano , Vitelli Alessandra , Colloca Stefano , Folgori Antonella , Raggiolli Angelo , Capone Stefania , Nason Martha C. , Douek Daniel C. , Roederer Mario , Seder Robert A. , Sullivan Nancy J. 
Published: November 2023

SummarySARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there’s a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways.
Printing, Characterising, and Assessing Transparent 3D Printed Lenses for Optical Imaging
Authors: Rooney Liam M. , Christopher Jay , Watson Ben , Kumar Yash Susir , Copeland Laura , Walker Lewis D. , Foylan Shannan , Amos William B. , Bauer Ralf , McConnell Gail 
Published: November 2023

AbstractHigh-quality lens production has involved subtractive manufacturing methods for centuries. These methods demand specialist equipment and expertise that often render custom high-grade glass optics inaccessible. We aimed to develop a low-cost, accessible, and reproducible method to manufacture high-quality three-dimensional (3D) printed lenses using consumer-grade technology. Various planoconvex lenses were produced using a consumer-grade 3D printer and low-cost spin coating setup, and printed lenses were compared to commercial glass counterparts. A range of mechanical and optical methods are introduced to determine the surface quality and curvature of 3D printed lenses. Amongst others, high-resolution interference reflection microscopy methods were used to reconstruct the convex surface of printed lenses and quantify their radius of curvature. The optical throughput and performance of 3D printed lenses were assessed using optical transmissivity measurements and classical beam characterisation methods. We determined that 3D printed lenses had comparable curvature and performance to commercial glass lenses. Finally, we demonstrated the application of 3D printed lenses for brightfield transmission microscopy, resolving sub-cellular structures over a 2.3 mm field-of-view. The high reproducibility and comparable performance of 3D printed lenses present great opportunities for additive manufacturing of bespoke optics for low-cost rapid prototyping and improved accessibility to high-quality optics in low-resource settings.
Glutathione overproduction mediates lymphoma initiating cells survival and has a sex-dependent effect on lymphomagenesis
Authors: Alberto H.-Alcántara , Kourani Omar , Marcos-Jiménez Ana , Martínez-Núñez Patricia , Herranz-Martín Estela , Fuentes Patricia , Toribio María Luisa , Muñoz-Calleja Cecilia , Iglesias Teresa , Campanero Miguel R. 
Published: November 2023

AbstractLymphoid tumor patients often exhibit resistance to standard therapies or experience rapid relapse post-remission. Tumor-initiating cells (TICs), a small fraction of the tumor cell population known for their self-renewal capacity and resistance to cancer therapies, likely drive tumor relapse. Tumorigenicity strongly correlates with growth in soft gels and TICs are the only cancer cells capable of growing in soft gels. Targeting pathways critical for TIC survival or growth holds promise for improving cancer treatment outcomes but TIC biology remains poorly understood. Here, we show that culturing lymphoid cells in soft hydrogels triggers reactive oxygen species (ROS) production, leading to non-tumor lymphoid cell death while enabling the survival and proliferation of a subset of lymphoma/leukemia cells, TICs or TIC-like cells. Treatment with the antioxidant N-acetylcysteine inhibits this lethality and even promotes the growth of primary non-tumor lymphoid cells in soft gels. Some lymphoma cells escape ROS-induced lethality by boosting antioxidant glutathione production, a response not seen in non-tumor cells. Reducing glutathione production in lymphoma cells, either through pharmacological inhibition of glutamate cysteine ligase (GCL), the enzyme catalyzing the rate-limiting step in glutathione biosynthesis, or via knockdown ofGCLC, the GCL catalytic subunit, sharply decreased cell viability and proliferation in soft gels and tumor growth in immunodeficient mice. Tumor cells from B-cell lymphoma/leukemia patients and λ-MYC mice, a B-cell lymphoma mouse model, overproduce glutathione. Importantly, pharmacological GCL inhibition hindered lymphoma growth in female λ-MYC mice, suggesting that this treatment holds promise as a therapeutic strategy for female lymphoma/leukemia patients.
Adolescent Thalamocortical Inhibition Alters Prefrontal Excitation-Inhibition Balance
Authors: Petersen David , Raudales Ricardo , Silva Ariadna Kim , Kellendonk Christoph , Canetta Sarah 
Published: November 2023

AbstractAdolescent inhibition of thalamo-cortical projections from postnatal day P20-50 leads to long lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuit connectivity during adolescence. Here, we used chemogenetic tools to inhibit thalamo-prefrontal projections in the mouse from P20-35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target twenty-four hours later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III nucleus accumbens (NAc) and layer V/VI medio-dorsal thalamus projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but not excitatory currents was enhanced in contralateral mPFC-projecting neurons. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition in each cell was only changed in the contralateral mPFC projections. This finding suggests homeostatic regulation occurs within subcortically but not intracortical callosally-projecting neurons. Increased inhibition of intra-prefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation. Finally, we observed cognitive deficits in the adult mouse using this narrowed window of thalamocortical inhibition (P20-P35).Significance StatementConnectivity between two brain regions, the thalamus and the prefrontal cortex, has been found to be reduced in patients with schizophrenia. Neuronal activity in thalamo-cortical projections is important for the proper development of sensory cortices. How thalamo-cortical activity regulates prefrontal cortex development is less well understood. Here, we show that decreasing activity in thalamo-prefrontal projections in mice during early adolescence alters synaptic connectivity to distinct neuronal projections within the prefrontal cortex that are already evident in adolescence. While some of these changes can be explained by reduced thalamo-cortical projections, other adaptations are intrinsic to the prefrontal cortex. These findings implicate adolescence as a critical period of cortical development and demonstrate this period as a potential target for therapeutic intervention.