bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humidity-dependent structural adaptations ofDrosophila melanogasterhygrosensilla
Authors: Giri Ganesh , Enjin Anders 
Published: November 2024

AbstractUnderstanding how organisms detect environmental humidity remains a fundamental problem in sensory biology. While specialized sensory neurons in insect antennae can detect changes in humidity, the mechanism underlying this ability is not fully understood. Here, we present an integrated approach combining precise humidity control, rapid cryo-preservation, and serial block-face scanning electron microscopy (SBF-SEM) to investigate the ultrastructure of hygrosensilla in the vinegar flyDrosophila melanogaster. We developed a deep learning-based segmentation pipeline to analyze three-dimensional structural features of sensilla exposed to different humidity conditions at stable temperature. Our analysis reveals consistent differences in sensilla width between high (80% RH) and low (26% RH) humidity conditions across all chambers of the sacculus. Additionally, we identified chamber-specific patterns in sensilla tapering, indicating specialized structural adaptations across different sensilla populations. The observed structural changes suggest a potential role for mechanical transduction in humidity sensing. This study establishes a technical framework for high-resolution analysis of sensory organs while providing new insights into the structural basis of humidity detection. Our findings advance our understanding of how specialized sensory organs might transduce environmental signals into neural responses.
Slow and fast gamma oscillations show phase-amplitude coupling with distinct high-frequency bands in macaque primary visual cortex
Authors: Prabhu Pooja , Ray Supratim 
Published: November 2024

AbstractGamma oscillations (25-70 Hz) can be induced in the visual cortex by presenting stimuli like gratings. Large stimuli produce two distinct gamma oscillations in primate primary visual cortex (V1) – slow (25-40 Hz) and fast (40-70 Hz), possibly due to different interneuronal networks. While fast-gamma has been shown to strongly lock spikes, slow-gamma does not, and hence its role in cortical processing is unclear. Here, we studied potential influence of gamma rhythms on neural activity using phase-amplitude coupling (PAC). We recorded spikes, local field potential and electrocorticogram (ECoG) from V1 of two adult female monkeys while presenting stimuli that simultaneously induced both gamma rhythms, and developed a novel method that reduces the influence of spike-related-transient on PAC. Interestingly, while fast-gamma showed coupling with frequencies above 150 Hz, reflecting spike-locking, slow-gamma showed PAC in a distinct frequency range between 80-150 Hz, which was especially prominent in ECoG. PAC varied with orientation and spatial frequency in the same way as power in the respective frequency bands, confirming dissociation in the coupling of the two gamma rhythms. Thus, fast-gamma could be more involved in spike-locking, while slow-gamma could represent a modulatory signal acting by amplitude modulation between 80-150 Hz at a more global scale.Significance StatementGamma oscillations in the visual cortex can be induced by stimuli like gratings, producing two distinct gamma oscillations: slow (20-40 Hz) and fast (40-70 Hz). While fast-gamma strongly locks spikes, the role of slow gamma is unclear. Oscillations have been proposed to influence processing through phase-amplitude coupling (PAC). We recorded spikes, local field potential (LFP) and electrocorticogram (ECoG) from female monkeys and developed a new method to study PAC. While fast-gamma showed PAC with 150-500 Hz, reflecting spike-locking, we found PAC between slow-gamma and 80-150 Hz, which was especially strong in ECoG. The two PAC signatures varied differently with stimulus, reflecting distinct origins. Thus, while fast-gamma could lock spikes, slow-gamma could modulate amplitudes between 80-150 Hz at a global scale.
Gaze when walking to grasp an object in the presence of obstacles
Authors: Voudouris Dimitris , Brenner Eli 
Published: November 2024

AbstractPeople generally look at positions that are important for their current actions, such as objects they intend to grasp. What if there are obstacles on their path to such objects? We asked participants to walk into a room and pour the contents of a cup placed on a table into another cup elsewhere on the table. There were two small obstacles on the floor between the door and the table. There was a third obstacle on the table near the target cup. Participants mainly looked at the items on the table, but as they approached and entered the room they often looked at the floor near the obstacles, although there was nothing particularly informative to see there. They relied on peripheral vision and memory of where they had seen obstacles to avoid kicking the obstacles. From well before participants crossed the obstacles, they primarily looked at the object that they intended to grasp. We conclude that people look at positions at which they plan to interact with the environment in a specific manner, rather than at items that constrain such interactions.
Rho GTPases signaling mediates aggressiveness and differentiation in neuroblastoma tumors
Authors: Gómez-Muñoz María A. , Ojeda-Puertas Mónica , Luna-Ramírez Luis , Amador-Álvarez Aida , Rodríguez-Prieto Ismael , Cordero Varela Juan Antonio , Pardal Ricardo , Vega Francisco M. 
Published: November 2024

AbstractBackgroundNeuroblastoma (NB) is a pediatric cancer with highly variable outcomes, necessitating improved understanding of the molecular pathways driving its progression. Intratumor cellular heterogeneity related to neural differentiation has emerged as a defining characteristic that can explain its aggressive behavior. Although recurrent driver mutations are not typically observed in these tumors, Rho GTPases signaling genes have been identified as one of the most frequently mutated in aggressive NB cases. Rho GTPases are key regulators of cell morphology, migration, and differentiation, yet their role in NB remains underexplored. This study aims to comprehensively evaluate the expression and clinical significance of Rho GTPase signaling networks in NB tumors.MethodsWe analyzed the expression profiles of Rho GTPases, their regulators, and effectors, across multiple NB patient cohorts. Gene expression correlations with clinical parameters were assessed, and bioinformatics analyses were employed to identify gene expression patterns and interactions in tumors. Functional studies were performed in NB cell lines and in vivo models to validate the role of key Rho GTPases, including Cdc42, in NB progression and differentiation.ResultsOur analysis revealed widespread dysregulation of Rho GTPase signaling in NB tumors. Specific GTPases, such asRHOAorRHOV, were upregulated in advanced disease stages, while others, includingRHOB,RHOUandCDC42, were downregulated and associated with poor prognosis. A minimal Rho-related gene signature was identified as a strong predictor of NB patient survival. Functional validation highlighted Cdc42 as a key regulator of NB differentiation, where its downregulation was necessary for maintaining the malignant, undifferentiated phenotype of NB cells. We also identifiedARHGAP31/CdGAP as a critical regulator of Cdc42 in NB progenitor cells, suggesting a mechanism for Cdc42 suppression in aggressive NB.ConclusionsAn important role for Rho GTPase signaling in NB progression is revealed, providing a foundation for further exploration of Rho GTPase-targeted therapies in NB. In particular, Cdc42 signaling intervene in the balance between differentiation and stemness in NB cells, suggesting specific signaling events controlling the identity and plasticity of NB cells.
Inactive structures of the vasopressin V2 receptor reveal distinct antagonist binding modes for Tolvaptan and Mambaquaretin toxin
Authors: Fouillen Aurélien , Bous Julien , Couvineau Pierre , Orcel Hélène , Mary Charline , Pierre Timothé , Mendre Christiane , Gilles Nicolas , Schulte Gunnar , Granier Sébastien , Mouillac Bernard 
Published: November 2024

AbstractAntagonists of the arginine-vasopressin (AVP) V2 receptor (V2R) are key therapeutic compounds to treat hyponatremia or polycystic kidney diseases. Compounds such as Tolvaptan (TVP) and Conivaptan are marketed drugs but their mechanisms of inhibition are not known. In addition, TVP presents unwanted side effects such as serious liver injury. Conivaptan also targets AVP V1a receptor subtype and thus is not selective to V2R. To develop novel molecules with less side effects and better selectivity, rational drug design based on experimental three-dimensional G protein-coupled receptor (GPCR) structures is a powerful and successful avenue. The lack of antagonist-bound V2R structures has however impaired this strategy for this GPCR. To fill this gap of knowledge, we solved here the cryo-electron microscopy structures of the vasopressin V2R in complex with two selective antagonists, the nonpeptide TVP and the green mamba snake Mambaquaretin toxin (MQ1). Both ligands, known to be competitive, bind into the orthosteric AVP binding site but with substantial differences. The small molecule binds deeper than MQ1, and directly contacts the toggle switch residue W2846.48in the transmembrane domain 6 (TM6), whereas the peptide Kunitz- fold toxin presents more extensive contacts with the receptor through additional interactions with extracellular and transmembrane residues. As anticipated from the pharmacological properties of TVP and MQ1, both structures represent inactive conformations of the V2R. Their comparison with those of the active AVP-bound V2R reveals the molecular mechanisms modulating receptor activity. Finally, the structure of the V2R bound to a mini-protein such as MQ1 opens a new pharmacology era in the field of water homeostasis and renal diseases.
Modelling the prebiotic origins of regulation & agency in evolving protocell ecologies
Authors: Shirt-Ediss Ben , Ferrero-Fernández Arián , De Martino Daniele , Bich Leonardo , Moreno Alvaro , Ruiz-Mirazo Kepa 
Published: November 2024

SummaryHow did natural systems develop the first mechanisms of regulation and what for? How could they turn into adaptive agents in a minimal (though deeply meaningful) biological sense? A novel simulation platform, ‘Araudia’, has been implemented to address these questions, which are deeply interrelated, in a prebiotic scenario where metabolically diverse protocells are allowed to modify their dynamic behaviour in response to changes in their boundary conditions (e.g., nutrient concentrations in the medium) and/or in the activity of other protocells, including cross-feeding relationships. We extend ‘consumer-resource models’ (CRMs) to a stochastic evolutionary framework in which novelty appearsbottom-up(i.e., from small changes at the individual protocell level), and a short-term memory may also come forth and spread in the population, to demonstrate that simple adaptive/learning processes can have relevant effects at somatic times (i.e., within the lifetime of single protocells). Our interest in exploring the interplay between metabolic-physiological aspects and ecological-evolutionary ones derives from the fact that it provides a complex causal domain, where various spatial and temporal scales intermingle, and where both theactualand thepotential(pathways/behaviours) must be considered. It is in such a complex domain where the appearance of regulation acquires full significance, as an effective means to navigate phenotypic spaces that become too big for unguided exploration, given the large number of possible functionalities (or functional states) accessible to each proto-cellular agent. The results obtained for several minimalist cases below show that, despite the non-trivial combination of --both endogenous and exogenous--factors involved in the constitution of regulatory mechanisms, these are bound to play a critical role in the survival of infra-biological systems, especially under rapidly changing environmental conditions that longer-term adaptive mechanisms would not be able to cope with.
Differential Engagement of Associative-Limbic and Sensorimotor Regions of the Cerebellum and Basal Ganglia in Explicit vs. Implicit Emotional Processing
Authors: Ceravolo Leonardo , Thomasson Marine , Constantin Ioana Medeleine , Chassot Émilie , Pierce Jordan , Cionca Alexandre , Grandjean Didier , Assal Frédéric , Péron Julie 
Published: November 2024

AbstractEmotional prosody processing involves multiple brain regions, but the specific roles of the cerebellum and basal ganglia in explicit (conscious) and implicit (incidental) tasks are not well known or understood. This study investigated how the cerebellum and basal ganglia contribute to explicit (emotion categorization) and implicit (gender categorization) processing of emotional prosody. Twenty-eight healthy French-speaking participants underwent high-resolution functional MRI while performing a vocal emotion processing task under such implicit and explicit conditions. Behavioral data analyses indicated greater accuracy in the gender discrimination task (implicit processing). Neuroimaging partially supported our hypothesis according to which explicit emotion processing yielded increased activations in associative-limbic regions (e.g., inferior frontal gyrus, Crus I and caudate) linked to higher-order functions, while implicit emotion processing engaged sensorimotor regions (primary motor cortex, primary somatosensory cortex) and areas associated with automatic processing (putamen, posterior insula, cerebellar lobules VIIIa-b and IX). Unexpected activity during task conditions suggest motor preparation effects and more complex brain network dynamics. These results challenge modular views of brain function and highlight the need to consider emotional processing as complex, dynamic, network-based interactions.
Engineering of soluble bacteriorhodopsin
Authors: Nikolaev Andrey , Orlov Yaroslav , Tsybrov Fedor , Kuznetsova Elizaveta , Shishkin Pavel , Kuzmin Alexander , Mikhailov Anatoly , Galochkina Yulia S. , Anuchina Arina , Chizhov Igor , Semenov Oleg , Kapranov Ivan , Borshchevskiy Valentin , Remeeva Alina , Gushchin Ivan 
Published: November 2024

AbstractBacteriorhodopsin is a seven-helical light-driven proton pump and a model membrane protein. Here, we report engineering of soluble analogues of bacteriorhodopsin, NeuroBRs, which bind retinal and photocycle under illumination. We also report the crystallographic structure of NeuroBR_A, determined at anisotropic resolution reaching 1.76 Å, that reveals a conserved chromophore binding pocket and tertiary structure. Our results highlight the power of modern protein engineering approaches and pave the way towards wider development of molecular tools derived from membrane proteins.
«Studiesin vitroein vivoof Phage Therapy Medical Products (PTMPs) targeting clinical strains ofKlebsiella pneumoniaebelonging to the clone ST512»
Authors: Bleriot Inés , Blasco Lucía , Fernández-Grela Patricia , Fernández-García Laura , Armán Lucia , Ibarguren Clara , Ortiz-Cartagena Concha , Barrio-Pujante Antonio , Paño José Ramón , Oteo-Iglesias Jesús , Tomás María 
Published: November 2024

ABSTRACTThe widespread incidence of antimicrobial resistance has created renewed interest in the use of alternative antimicrobial treatments such as phage therapy. Phages are viruses that infect bacteria and generally have a narrow bacteria host-range. Combining phages with antibiotics can prevent the emergence of bacterial resistance. The aim of the present study was to develop phage therapy medical products (PTMPs) targeting clinical isolates of carbapenems-producingKlebsiella pneumoniaebelonging to the high-risk clone ST512. From a collection of twenty-two seed of lytic phages sequenced belonging to MePRAM collection, four were used to generate PTMPs (CAC_Kpn1 and CAC_Kpn2). These PTMPs were partly active against three of the clinical strains of clone ST512 (A, B and C). The use of Appelmans method in the CAC_Kpn1_ad (adapted CAC_Kpn1) yielded a significant increase in the efficacy against strain A, while adapted CAC_Kpn2 (CAC_Kpn2_ad) only effectively reduced bacterial survival when combined with ½ x MIC ß-lactam antibiotic meropenem for 24 h in clinical strains B and C, showed after this time, resistance to PTMPs. In addition, the amounts of endotoxin released by the PTMPs were quantified and subsequently reduced in preparation forin vivouse of the PTMPs inGalleria mellonellainfection model confirming thein vitroresults from the CAC_Kpn1_ad and CAC_Kpn2_ad.
Organization of the apical extracellular matrix during tubular organ formation
Authors: Woodward J. Luke , Matthew Jeffrey , Vishwakarma Vishakha , Xiao Ying , Chung SeYeon 
Published: November 2024

AbstractThe apical extracellular matrix (aECM) plays a critical role in epithelial tube morphogenesis during organ formation, but its composition and organization remain poorly understood. Using theDrosophilaembryonic salivary gland (SG) as a model, we identify Papss, an enzyme that synthesizes the universal sulfate donor PAPS, as a critical regulator of tube lumen expansion.Papssmutants show a disorganized apical membrane, condensed aECM, and disruptions in Golgi structures and intracellular trafficking. Additionally, we identify two zona pellucida (ZP) domain proteins, Piopio (Pio) and Dumpy (Dpy), as key components of the SG aECM. In the absence ofPapss, Pio is gradually lost in the aECM, while the Dpy-positive aECM structure is condensed and dissociates from the apical membrane, leading to a thin lumen. Mutations indpyorpio, or inNotopleural, which encodes a matriptase that cleaves Pio to form the luminal Pio pool, result in a SG lumen with alternating bulges and constrictions, with the loss ofpioleading to the loss of Dpy in the lumen. Our findings underscore the essential role of sulfation in organizing the aECM during tubular organ formation and highlight the mechanical support provided by ZP domain proteins in maintaining luminal diameter.
Yeasts prefer daycares and molds prefer private homes
Authors: Kauserud Håvard , Martin-Sanchez Pedro M. , Estensmo Eva Lena , Botnen Synnøve , Morgado Luis , Maurice Sundy , Høiland Klaus , Skrede Inger 
Published: November 2024

AbstractIndoor fungi can cause negative health effects due to the production of toxins or volatiles that trigger the immune system of the occupants. To what degree indoor fungi (mycobiomes) differ between buildings with different usage is poorly known. Here, we compare the indoor mycobiomes in 123 children’s daycare centers and 214 private homes throughout Norway, as revealed by metabarcoding of DNA extracted from dust samples collected by community scientists. Although the fungal richnessper sewas similar in dust samples from daycares and homes, the fungal community composition differed. Yeast fungi, distributed mainly across the orders Saccharomycetales, Filobasidiales and Tremellales, were proportionally more abundant in the daycares, while filamentous fungi, including spore-producing molds such asAspergillus, PenicillumandCladosporium, were relatively more abundant in homes. Number of occupants, which is considerably higher in daycares, correlated significantly with the fungal community shift. We hypothesize that the density of occupants and their age distribution drive the systematic difference of yeasts and filamentous fungi in the two building types.ImportanceWorldwide, people spend most of their time indoors; in their homes, workplaces, schools and daycares. The indoor environment can thus largely influence our health. In this study, we revealed that number of occupants and possibly their age distribution are important explanatory variables for the fungal communities of the indoor environments in homes and daycares. Knowledge of these communities are important for further studies on how fungal diversity affect our health.
Sub-therapeutic Concentrations of Antibiotics Induce Prophage-driven Superinfection Exclusion and Fitness Cost inPseudomonas aeruginosa
Authors: Bucher Michael J. , Puente Cristian P. , Sehdev Naveen , Czyż Daniel M. 
Published: November 2024

AbstractBacteria and other microbes can naturally produce antibiotics within their native soil environment, but often at sub-inhibitory concentrations; consequently, the exact role of antibiotics within bacterial native communities remains unknown. We have shown that subtherapeutic quantities of naturally occurring antibiotics can induce thePseudomonasprophage Pf4, and superinfection ofPseudomonas aeruginosacells by this phage leads to their reduced virulence, as demonstrated by impaired twitching motility, compromised macrophage evasion, and increased killing by macrophagesin vitro. Thus, the production of subtherapeutic concentrations of antibiotics by environmental microbes may provide the producers an evolutionary advantage associated with reduced fitness induced by prophages in the competing bacteria. Collectively, these results reveal the role of naturally occurring antibiotics in altering fitness by phage-mediated superinfection exclusion and provide potential clinical implications in the application of phage therapy.Significance StatementThis study provides insights into the mechanisms by which sub-inhibitory concentrations of environmentally-produced antibiotics inducePseudomonas aeruginosaprophages, revealing a potential evolutionary strategy for competitive advantage among bacteria. By activating prophages, antibiotics can induce fitness defects in neighboring bacteria, impacting their motility, phagocytosis, and survival within macrophages. Such previously unrecognized role for environmental antibiotics in bacterial ecosystems may offer insights into enhancing phage therapy by exploiting phage-antibiotic synergies. Understanding phage-host interactions can enhance therapeutic strategies to mitigate bacterial infections and antimicrobial resistance.
Antibiotic-free whole-cell biocatalytic fermentation:Escherichia coliwith surface-displayed PETases for sustainable plastic degradation
Authors: Romero-Orejon Katherine , Karbalaei-Heidari Hamid Reza , Budisa Nediljko , Levin David 
Published: November 2024

AbstractPlastic pollution has increasingly burdened the environment, driving the need for natural degradation platforms that utilize microbial enzymes to break plastics down into monomers. In this study, we introduce a novel approach usingEscherichia colias a fermentative, antibiotic-free whole-cell biocatalyst with surface-displayed, genomically integrated PETases for efficient plastic degradation. PETases, a class of esterases, catalyze the hydrolysis of polyethylene terephthalate (PET) into mono-2-hydroxyethyl terephthalate (MHET). Surface display of these enzymes was achieved via gene fusions with an N-terminal cysteine (Cys) triacylated anchor, mediated by the Braun lipoprotein (Lpp) signal peptide. To circumvent issues associated with plasmids, - such as genetic instability and reliance on antibiotics - we used a Type I-F CRISPR-associated transposase to insert the genes directly into specificE. coligenome sites. Proper enzyme display and activity on theE. colisurface were confirmed through enzyme activity tests, Western blotting, and flow cytometry, with cells retaining PET degradation ability over multiple generations. High-performance liquid chromatography (HPLC) analysis assessed degradation efficiency, identifying byproducts such as bis (2-hydroxyethyl) terephthalate and terephthalic acid. This study establishes a proof-of-concept for efficient plastic degradation using engineered bacteria as robust, sustainable, and genomically stable whole-cell biocatalysts, providing a promising platform for addressing plastic waste management.Graphical AbstractOne-sentence AbstractEscherichia coliwas engineered as a fermentative, antibiotic-free whole-cell biocatalyst, featuring surface-displayed and genomically integrated PETases for efficient plastic degradation. This innovative approach has the potential to transform plastic recycling by enabling sustainable, large-scale degradation of plastic waste through environmentally friendly microbial systems.