bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell class-specific electric field entrainment of neural activity
Authors: Lee Soo Yeun , Kozalakis Konstantinos , Baftizadeh Fahimeh , Campagnola Luke , Jarsky Tim , Koch Christof , Anastassiou Costas A. 
Published: February 2023

SummaryElectric fields affect the activity of neurons and brain circuits, yet how this interaction happens at the cellular level remains enigmatic. Lack of understanding on how to stimulate the human brain to promote or suppress specific activity patterns significantly limits basic research and clinical applications. Here we study how electric fields impact the subthreshold and spiking properties of major cortical neuronal classes. We find that cortical neurons in rodent neocortex and hippocampus as well as human cortex exhibit strong and cell class-dependent entrainment that depends on the stimulation frequency. Excitatory pyramidal neurons with their typically slower spike rate entrain to slow and fast electric fields, while inhibitory classes like Pvalb and SST with their fast spiking predominantly phase lock to fast fields. We show this spike-field entrainment is the result of two effects: non-specific membrane polarization occurring across classes and class-specific excitability properties. Importantly, these properties of spike-field and class-specific entrainment are present in cells across cortical areas and species (mouse and human). These findings open the door to the design of selective and class-specific neuromodulation technologies.
PIQLE: protein-protein interface quality estimation by deep graph learning of multimeric interaction geometries
Authors: Shuvo Md Hossain , Karim Mohimenul , Roche Rahmatullah , Bhattacharya Debswapna 
Published: February 2023

AbstractAccurate modeling of protein-protein interaction interface is essential for high-quality protein complex structure prediction. Existing approaches for estimating the quality of a predicted protein complex structural model utilize only the physicochemical properties or energetic contributions of the interacting atoms, ignoring evolutionarily information or inter-atomic multimeric geometries, including interaction distance and orientations. Here we present PIQLE, a deep graph learning method for protein-protein interface quality estimation. PIQLE leverages multimeric interaction geometries and evolutionarily information along with sequence- and structure-derived features to estimate the quality of the individual interactions between the interfacial residues using a multihead graph attention network and then probabilistically combines the estimated quality of the interfacial residues for scoring the overall interface. Experimental results show that PIQLE consistently outperforms existing state-of-the-art methods on multiple independent test datasets across a wide range of evaluation metrics. Our ablation study reveals that the performance gains are connected to the effectiveness of the multihead graph attention network in leveraging multimeric interaction geometries and evolutionary information along with other sequence- and structure-derived features adopted in PIQLE. An open-source software implementation of PIQLE, licensed under the GNU General Public License v3, is freely available athttps://github.com/Bhattacharya-Lab/PIQLE.
A computational investigation on Rho-related GTP-binding protein RhoB through molecular modeling and molecular dynamics simulation study
Authors: Paul Shamrat Kumar , Nahar Metu Chowdhury Lutfun , Sutihar Sunita Kumari , Saddam Md. , Paul Bristi , Kabir Md. Lutful , Uddin Helal Md Mostofa 
Published: February 2023

BackgorundRhoB is a key member of the Rho family of isoprenylated small GTPases which modulate the cellular cytoskeletal organization. It has a crucial role in the neoplastic apoptotic mechanism after DNA damage. Due to the unavailability of 3D structure in the protein data bank database, in this study, we evaluated the structure of a protein, Rho-related GTP-binding protein RhoB.ResultsRhoB has a predicted pI of 5.10, indicating that it is acidic. The GMQE value was used to compute the target–template alignment, and 6hxu.1.A from Homo sapiens was chosen as the template structure, with the model construction task completed using swiss-model. The structural compactibility and stability were revealed after a 100ns molecular dynamics simulation using GROMACA employing the OPLS-AA force field. PCA analysis found residues that are relevant based on their fluctuation acitivity while their location is between 100-110 and 140-150.ConclusionThis study will benefit future investigations addressing the association between gene mutation and abnormalities generated by protein Rho-related GTP-binding protein RhoB in apoptotic events by offering insight into the biophysical phenomenon of Rho-related GTP-binding protein RhoB inhibitors.
Spatiotemporal dynamics of sensory neuron and Merkel-cell remodeling are decoupled during epidermal homeostasis
Authors: Clary Rachel C. , Jenkins Blair A. , Lumpkin Ellen A. 
Published: February 2023

SummaryAs the juncture between the body and environment, epithelia are both protective barriers and sensory interfaces that continually renew. To determine whether sensory neurons remodel to maintain homeostasis, we usedin vivotwo-photon imaging of somatosensory axons innervating Merkel cells in adult mouse skin. These touch receptors were highly plastic: 63% of Merkel cells and 89% of branches appeared, disappeared, grew, regressed and/or relocated over a month. Interestingly, Merkel-cell plasticity was synchronized across arbors during rapid epithelial turnover. When Merkel cells remodeled, the degree of plasticity between Merkel-cell clusters and their axons was well correlated. Moreover, branches were stabilized by Merkel-cell contacts. These findings highlight the role of epithelial-neural crosstalk in homeostatic remodeling. Conversely, axons were also dynamic when Merkel cells were stable, indicating that intrinsic neural mechanisms drive branch plasticity. Two terminal morphologies innervated Merkel cells: transient swellings called boutons, and stable cups termed kylikes. InAtoh1knockout mice that lack Merkel cells, axons showed higher complexity than control mice, with exuberant branching and no kylikes. Thus, Merkel cells limit axonal branching and promote branch maturation. Together, these results reveal a previously unsuspected high degree of plasticity in somatosensory axons that is biased, but not solely dictated, by plasticity of target epithelial cells. This system provides a platform to identify intrinsic and extrinsic mechanisms that govern axonal patterning in epithelial homeostasis.
Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain
Authors: Swanson Molly E V , Mrkela Miran , Murray Helen C , Cao Maize C , Turner Clinton , Curtis Maurice A , Faull Richard L M , Walker Adam K , Scotter Emma L 
Published: February 2023

AbstractMicroglia, the innate immune cells of the brain, are activated by damage or disease. In mouse models of amyotrophic lateral sclerosis (ALS), microglia shift from neurotrophic to neurotoxic states with disease progression. It remains unclear how human microglia change relative to the TAR DNA-binding protein 43 (TDP-43) aggregation that occurs in 97% of ALS cases. Here we examine spatial relationships between microglial activation and TDP-43 pathology in brain tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from the Neurological Foundation Human Brain Bank was obtained from 10 control and 10 ALS cases in parallel with brain tissue from a bigenicNFFH-tTA/tetO-hTDP-43ΔNLS (rNLS) mouse model of ALS at disease onset, early disease, and late disease stages. The spatiotemporal relationship between microglial activation and ALS pathology was determined by investigating microglial functional marker expression in brain regions with low and high TDP-43 burden at end-stage human disease: hippocampus and motor cortex, respectively. Sections were immunohistochemically labelled with a two-round multiplexed antibody panel against; microglial functional markers (L-ferritin, HLA-DR, CD74, CD68, and Iba1), a neuronal marker (NeuN), an astrocyte marker (GFAP), and pathological phosphorylated TDP-43 (pTDP-43). Single-cell levels of microglial functional markers were quantified using custom analysis pipelines and mapped to anatomical regions and ALS pathology. We identified a significant increase in microglial Iba1 and CD68 expression in the human ALS motor cortex, with microglial CD68 being significantly correlated with pTDP-43 pathology load. We also identified two subpopulations of microglia enriched in the ALS motor cortex that were defined by high L-ferritin expression. A similar pattern of microglial changes was observed in the rNLS mouse, with an increase first in CD68 and then in L-ferritin expression, with both occurring only after pTDP-43 inclusions were detectable. Our data strongly suggest that microglia are phagocytic at early-stage ALS but transition to a dysfunctional state at end-stage disease, and that these functional states are driven by pTDP-43 aggregation. Overall, these findings enhance our understanding of microglial phenotypes and function in ALS.
A Single Cell Genomics Atlas of theDrosophilaLarval Eye Reveals Distinct Developmental Timelines and Novel Markers for All Photoreceptor Subtypes
Authors: Bollepogu Raja Komal Kumar , Yeung Kelvin , Shim Yoon-Kyung , Li Yumei , Chen Rui , Mardon Graeme 
Published: February 2023

AbstractTheDrosophilaeye is a powerful model system to study principles of cell differentiation, proliferation, survival and morphogenesis. However, a high-resolution single cell genomics resource that accurately captures all major cell types of the larval eye disc and their spatiotemporal relationships is lacking. Here, we report transcriptomic and chromatin accessibility data for all known cell types in the developing eye. Photoreceptors appear as streams of cells that represent dynamic developmental timelines. Photoreceptor subtypes are transcriptionally distinct when they begin to differentiate, but then converge upon a common transcriptome just 24 hours later. We identify novel cell type-specific marker genes, enhancers and potential regulators, as well as genes with distinct R3 or R4 photoreceptor specific expression. Finally, we observe that photoreceptor chromatin accessibility is more permissive than non-neuronal lens-secreting cone cells, which show a more restrictive chromatin profile. This single cell genomics atlas will greatly empower theDrosophilaeye as a model system.
Nuclear Factor-Y is a Pervasive Regulator of Neuronal Gene Expression
Authors: Moreira Pedro , Papatheodorou Paul , Deng Shuer , Gopal Sandeep , Handley Ava , Powell David , Pocock Roger 
Published: February 2023

SUMMARYNervous system function relies on the establishment of complex gene expression programs that provide neuron-type-specific and core pan-neuronal features. These complementary regulatory paradigms are controlled by terminal selector and parallel-acting transcription factors (TFs), respectively. Here, we identify the Nuclear Factor Y (NF-Y) TF as a pervasive regulator of both neuron-type-specific and pan-neuronal gene expression. Mapping global NF-Y targets reveals direct binding to thecis-regulatory regions of pan-neuronal genes and terminal selector TFs. We show that NFYA-1 controls pan-neuronal gene expression directly through binding to CCAAT boxes in target gene promoters and indirectly by regulating the expression of terminal selector TFs. Further, we find that NFYA-1 regulation of neuronal gene expression is important for neuronal activity and motor function. Thus, our research sheds light on how global neuronal gene expression programs are buffered through direct and indirect regulatory mechanisms.
Position-dependent changes in phycobilisome abundance in multicellular cyanobacterial filaments revealed by Raman spectral analysis
Authors: Ishihara Jun-ichi , Imai Yuto 
Published: February 2023

AbstractThe one-dimensional filamentous cyanobacterium,Anabaenasp. PCC 7120, shows a simple pattern consisting of two types of cells under the nitrogen-deprived conditions. We found that the microbial pigment composition in differentiated (heterocyst) and undifferentiated cells (vegetative cells) were distinguished by using a Raman microscope. The Raman bands of phycocyanin and allophycocyanin were higher in the vegetative cells than those in the heterocysts. However, these bands were statistically lower in a part of vegetative cells, which were located far from a nearby heterocyst. That is, the pigment composition in the individual cells was affected by a locational information in a filament.
Coral disease and ingestion: investigating the role of heterotrophy in the transmission of pathogenicVibriospp. using a sea anemone (Exaiptasia pallida) model system
Authors: Norfolk William A. , Melendez-Declet Carolina , Lipp Erin K. 
Published: February 2023

AbstractUnderstanding disease transmission in corals can be complicated given the intracity of the holobiont and difficulties associated withex situcoral cultivation. As a result, most of the established transmission pathways for coral disease are associated with perturbance (i.e., damage) rather than evasion of immune defenses. Here we investigate ingestion as a potential pathway for the transmission of coral pathogens that evades the mucus membrane. Using sea anemones (Exaiptasia pallida) and brine shrimp (Artemiasp.) to model coral feeding, we tracked the acquisition of the putative pathogens,Vibrio alginolyticus, V. harveyi, andV. mediterraneiusing GFP-tagged strains.Vibriosp. were provided to anemones using three experimental exposures 1) direct water exposure alone, 2) water exposure in the presence of a food source (cleanArtemia), and 3) through a “spiked” food source (Vibrio-colonizedArtemia) created by exposingArtemiacultures to GFP-Vibriovia the ambient water overnight. Following a 3 h feeding/exposure duration, the level of acquiredGFP-Vibriowas quantified from anemone tissue homogenate. Ingestion of spikedArtemiaresulted in a significantly greater burden of GFP-Vibrioequating to an 829.7-fold, 3,108.2-fold, and 435.0-fold increase in CFU mL−1when compared to water exposed trials and a 206.8-fold, 62.2-fold, and 27.3-fold increase in CFU mL−1compared to water exposed with food trials forV. alginolyticus, V. harveyi, andV. mediterranei, respectively. These data suggest that ingestion can facilitate delivery of an elevated dose of pathogenic bacteria in cnidarians and may describe an important portal of entry for pathogens in the absence of perturbing conditions.ImportanceThe front line of pathogen defense in corals is the mucus membrane. This membrane coats the surface body wall creating a semi-impermeable layer that inhibits pathogen entry from the ambient water both physically and biologically through mutualistic antagonism from resident mucus microbes. To date, much of the coral disease transmission research has been focused on mechanisms associated with perturbance of this membrane such as direct contact, vector lesions (predation/biting), and waterborne exposure through preexisting lesions. The present research describes a transmission pathway that evades the defenses provided by this membrane allowing unencumbered entry of bacteria as in association with food. This pathway may explain an important portal of entry for emergence of idiopathic infections in otherwise healthy corals and can be used to improve management practices for coral conservation.
Consequence assessment and behavioral patterns of inhibition in decision-making: modelling its underlying mechanisms
Authors: Cecchini Gloria , DePass Michael , Baspinar Emre , Andujar Marta , Ramawat Surabhi , Pani Pierpaolo , Ferraina Stefano , Destexhe Alain , Moreno-Bote Rubén , Cos Ignasi 
Published: February 2023

ABSTRACTLearning to make adaptive decisions depends on exploring options, experiencing their consequence, and reassessing one’s strategy for the future. Although several studies have analyzed various aspects of value-based decision-making, most of them have focused on decisions in which gratification is cued and immediate. By contrast, how the brain gauges delayed consequence for decision-making remains poorly understood.To investigate this, we designed a decision-making task in which each decision altered future options. The task was organized in groups of consecutively dependent trials, and the participants were instructed to maximize the cumulative reward value within each group. In the absence of any explicit performance feedback, the participants had to test and internally assess specific criteria to make decisions. This task was designed to specifically study how the assessment of consequence forms and influences decisions as learning progresses. We analyzed behavior results to characterize individual differences in reaction times, decision strategies, and learning rates.We formalized this operation mathematically by means of a multi-layered decision-making model. By using a mean-field approximation, the first layer of the model described the dynamics of two populations of neurons which characterized the binary decision-making process. The other two layers modulated the decision-making policy by dynamically adapting an oversight learning mechanism. The model was validated by fitting each individual participants’ behavior and it faithfully predicted non-trivial patterns of decision-making, regardless of performance level.These findings provided an explanation to how delayed consequence may be computed and incorporated into the neural dynamics of decision-making, and to how learning occurs in the absence of explicit feedback.
Predicting long-term collective animal behavior with deep learning
Authors: Papaspyros Vaios , Escobedo Ramón , Alahi Alexandre , Theraulaz Guy , Sire Clément , Mondada Francesco 
Published: February 2023

AbstractDeciphering the social interactions that govern collective behavior in animal societies has greatly benefited from advancements in modern computing. Computational models diverge into two kinds of approaches: analytical models and machine learning models. This work introduces a deep learning model for social interactions in the fish speciesHemigrammus rhodostomus, and compares its results to experiments and to the results of a state-of-the-art analytical model. To that end, we propose a systematic methodology to assess the faithfulness of a model, based on the introduction of a set of stringent observables. We demonstrate that machine learning models of social interactions can directly compete against their analytical counterparts. Moreover, this work demonstrates the need for consistent validation across different timescales and highlights which design aspects critically enables our deep learning approach to capture both short- and long-term dynamics. We also show that this approach is scalable to other fish species.
Sotrovimab retains activity against SARS-CoV-2 Omicron variant BQ.1.1 in a non-human primate model
Authors: Hérate Cécile , Marlin Romain , Touret Franck , Dereuddre-Bosquet Nathalie , Donati Flora , Relouzat Francis , Junges Laura , Galhaut Mathilde , Dehan Océane , Sconosciutti Quentin , Nougairède Antoine , de Lamballerie Xavier , van der Werf Sylvie , Grand Roger Le 
Published: February 2023

AbstractThe SARS-CoV2 Omicron variants have acquired new Spike mutations leading to escape from the most of the currently available monoclonal antibody treatments reducing the options for patients suffering from severe Covid-19. Recently, bothin vitroandin vivodata have suggested that Sotrovimab could retain partial activity against recent omicron sub-lineage such as BA.5 variants, including BQ.1.1. Here we report full efficacy of Sotrovimab against BQ.1.1 viral replication as measure by RT-qPCR in a non-human primate challenge model.
CD4 T cells and neutrophils contribute to epithelial-mesenchymal transition in breast cancer
Authors: Sanlaville Amélien , Voissière Aurélien , Poujol Dominique , Hubert Margaux , André Suzanne , Perret Clémence , Foy Jean-Philippe , Goutagny Nadège , Malfroy Marine , Durand Isabelle , Châlons-Cottavoz Marie , Valladeau-Guilemond Jenny , Saintigny Pierre , Puisieux Alain , Caux Christophe , Michallet Marie-Cécile , Puisieux Isabelle , Bendriss-Vermare Nathalie 
Published: February 2023

ABSTRACTEpithelial-mesenchymal transition (EMT) is a central oncogenic mechanism, contributing both to transformation and metastatic dissemination. Inflammation and innate immune cells are known to favor EMT induction, but the role of adaptive immunity still remains unclear. Using an original murine mammary tumor model in immune cell subpopulation depletion experiments, we demonstrated that tumor cells maintain their epithelial phenotype in mice deficient for adaptive immune response, but undergo EMT in the presence of T-cells. This phenotypic conversion involves the major contribution of CD4 T cells, but not CD8 T cells nor B cells, undoubtedly demonstrating the pro-EMT role of CD4 T cells specifically among adaptive immune cells. Moreover, combined intra-tumor immune infiltrate and transcriptomic analyses of murine mammary tumors with various EMT phenotype revealed an inverse correlation between mesenchymal tumor cell and intratumoral neutrophil proportions, due to the reduced ability of mesenchymal cells to recruit neutrophils. Last, selectivein vivodepletion of neutrophils and transcriptomic analysis of human breast tumor cohorts demonstrated the pro-EMT role of neutrophils and suggest a cooperation with CD4 T cells in EMT promotion. Collectively, our data highlight a novel mechanism of EMT regulation by both innate and adaptive immune compartments.
Scribble, Lgl1, and myosin IIA interact with α/β-catenin to maintain epithelial junction integrity
Authors: Abedrabbo Maha , Sloomy Shirel , Abu-Leil Reham , Kfir-Cohen Einav , Ravid Shoshana 
Published: February 2023

AbstractE-cadherin, α- and β-catenin (E-cadherin-catenin complex) together with the cytoskeleton build the core of Adherens junctions (AJs). Scribble and Lgl1 are tumor suppressors, and it has been reported that Scribble stabilizes the coupling of E-cadherin with catenins promoting epithelial cell adhesion, but the molecular mechanism remains unknown. Here, we investigated the role of Scribble, Lgl1, and myosin-IIA (NMII-A) in AJ integrity. We show that Scribble, Lgl1, and NMII-A reside in a complex with the E-cadherin-catenin complex. Depletion of either Scribble or Lgl1 disrupts the localization of E-cadherin-catenin complex to AJs. aPKCζ phosphorylation of Lgl1 regulates AJ localization of Lgl1 and E-cadherin-catenin complex. Both Scribble and Lgl1 regulate the activation and recruitment of NMII-A at AJs. Finally, Scribble and Lgl1 are downregulated by TGFβ-induced EMT, and re-expression of Scribble or Lgl1 during EMT impedes its progression. Our results provide insight into the mechanism regulating AJ integrity by Scribble, Lgl1, and NMII-A.