bluuebunny/crossref_metadata_2025 huggingface dataset:
A closer look at high-energy X-ray-induced bubble formation during soft tissue imaging
Authors: Xian R. Patrick , Brunet Joseph , Huang Yuze , Wagner Willi L. , Lee Peter D. , Tafforeau Paul , Walsh Claire L.
Published: February 2023

Improving the scalability of tissue imaging throughput with bright, coherent X-rays requires identifying and mitigating artifacts resulting from the interactions between X-rays and matter. At synchrotron sources, long-term imaging of soft tissues in solution can result in gas bubble formation or cavitation, which dramatically compromises image quality and integrity of the samples. By combining in-line phase-contrast cineradiography withoperandogas chromatography, we were able to track the onset and evolution of high-energy X-ray-induced gas bubbles in ethanol-embedded soft tissue samples for tens of minutes (2 to 3 times the typical scan times). We demonstrate quantitatively that vacuum degassing of the sample during preparation can significantly delay bubble formation, offering up to a twofold improvement in dose tolerance, depending on the tissue type. However, once nucleated, bubble growth is faster in degassed than undegassed samples, indicating their distinct metastable states at bubble onset. Gas chromatography analysis shows increased solvent vaporization concurrent with bubble formation, yet the quantities of dissolved gases remain unchanged. Coupling features extracted from the radiographs with computational analysis of bubble characteristics, we uncover dose-controlled kinetics and nucleation site-specific growth. These hallmark signatures provide quantitative constraints on the driving mechanisms of bubble formation and growth. Overall, the observations highlight bubble formation as a critical, yet often overlooked hurdle in upscaling X-ray imaging for biological tissues and soft materials and we offer an empirical foundation for their understanding and imaging protocol optimization. More importantly, our approaches establish a top-down scheme to decipher the complex, multiscale radiation-matter interactions in these applications.

Significance statement

Better probing the X-ray radiation dose limit of bubble formation in biological tissue and developing mitigation methods is essential for improving imaging techniques involving X-ray, such as synchrotron X-ray tomography or crystallography. Here, we combinedoperandogas chromatography with in-line X-ray phase-contrast radiography on human lung and brain tissue to investigate bubble formation under high-energy X-ray irradiation. We demonstrate that vacuum degassing delays bubble nucleation up to a factor two, depending on the tissue type. Gas chromatography analysis showed increased solvent vaporization during bubble formation; however, the quantities of dissolved gases remained unchanged. Moreover, depending on the nucleation site, bubble growth can be geometrically constrained by sample microstructure, which influence its dynamics.
Spectral methods for prediction uncertainty quantification in Systems Biology
Authors: Deneer Anna , Molenaar Jaap , Fleck Christian
Published: February 2023

Uncertainty is ubiquitous in biological systems. These uncertainties can be the result of lack of knowledge or due to a lack of appropriate data. Additionally, the natural variability of biological systems caused by intrinsic noise, e.g. in stochastic gene expression, leads to uncertainties. With the help of numerical simulations the impact of these uncertainties on the model predictions can be assessed, i.e. the impact of the propagation of uncertainty in model parameters on the model response can be quantified. Taking this into account is crucial when the models are used for experimental design, optimisation, or decision-making, as model uncertainty can have a significant effect on the accuracy of model predictions. We focus here on spectral methods to quantify prediction uncertainty based on a probabilistic framework. Such methods have a basis in, e.g., computational mathematics, engineering, physics, and fluid dynamics, and, to a lesser extent, systems biology. In this chapter, we highlight the advantages these methods can have for modelling purposes in systems biology and do so by providing a novel and intuitive scheme. By applying the scheme to an array of examples we show its power, especially in challenging situations where slow converge due to high-dimensionality, bifurcations, and spatial discontinuities play a role.
Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa
Authors: Lowe Margaret M. , Cohen Jarish N. , Moss Madison I. , Clancy Sean , Adler James , Yates Ashley , Naik Haley B. , Pauli Mariela , Taylor Ian , McKay Austin , Harris Hobart , Kim Esther , Hansen Scott L. , Rosenblum Michael D. , Moreau Joshua M.
Published: February 2023

Structured Abstract

Background

Hidradenitis suppurativa (HS) skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu the biology and contribution of these cells in HS pathogenesis is unclear.

Objective

We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions.

Methods

We combined histological analysis, single-cell RNA-sequencing (scRNAseq), and spatial transcriptomic profiling of HS lesions to define the tissue microenvironment relative to B cell activity within this disease.

Results

Our findings identify tertiary lymphoid structures (TLS) within HS lesions and describe organized interactions between T cells, B cells, antigen presenting cells and skin stroma. We find evidence that B cells within HS TLS actively undergo maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells are primed to support the formation of TLS and facilitate B cell recruitment during HS.

Conclusion

Our data definitively demonstrate the presence of TLS in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed non-lymphoid tissue.
Targeted protein degradation via intramolecular bivalent glues
Authors: Hsia Oliver , Hinterndorfer Matthias , Cowan Angus D. , Iso Kentaro , Ishida Tasuku , Sundaramoorthy Ramasubramanian , Nakasone Mark A. , Imrichova Hana , Schätz Caroline , Rukavina Andrea , Husnjak Koraljka , Wegner Martin , Correa-Sáez Alejandro , Craigon Conner , Casement Ryan , Maniaci Chiara , Testa Andrea , Kaulich Manuel , Dikic Ivan , Winter Georg E. , Ciulli Alessio
Published: February 2023

Targeted protein degradation is a pharmacological modality based on the induced proximity of an E3 ubiquitin ligase and a target protein to promote target ubiquitination and proteasomal degradation. This has been achieved either via bifunctional compounds (PROTACs) composed of two separate warheads that individually bind the target and E3 ligase, or via molecular glues that monovalently bind either the ligase or the target1–4. Using orthogonal genetic screening, biophysical characterization, and structural reconstitution, we investigate the mode of action of bifunctional BRD2/4 degraders (IBG1-4) and find that – instead of connecting target and ligasein transas PROTACs do – they simultaneously engage two adjacent domains of the target proteinin cis. This conformational change glues BRD4 to the E3 ligases DCAF11 or DCAF16, leveraging intrinsic target-ligase affinities which, albeit pre-existing, do not translate to BRD4 degradation in absence of compound. Structural insights into the ternary BRD4:IBG1:DCAF16 complex guided the rational design of improved degraders of low picomolar potency. We thus introduce a new modality in targeted protein degradation, termed intramolecular bivalent glues (IBGs), which work by bridging protein domains to enhance surface complementarity with E3 ligases for productive ubiquitination and degradation.
Dephosphorylation of 4EBP1/2 Induces Prenatal Neural Stem Cell Quiescence
Authors: Geben Laura C. , Brockman Asa A. , Chalkley Mary Bronwen L. , Sweet Serena R. , Gallagher Julia E. , Scheuing Alexandra L. , Simerly Richard B. , Ess Kevin C. , Irish Jonathan M. , Ihrie Rebecca A.
Published: February 2023

A limiting factor in the regenerative capacity of the adult brain is the abundance and proliferative ability of neural stem cells (NSCs). Adult NSCs are derived from a subpopulation of embryonic NSCs that temporarily enter quiescence during mid-gestation and remain quiescent until postnatal reactivation. Here we present evidence that the mechanistic/mammalian target of rapamycin (mTOR) pathway regulates quiescence entry in embryonic NSCs of the developing forebrain. Throughout embryogenesis, two downstream effectors of mTOR, p-4EBP1/2 T37/46 and p-S6 S240/244, were mutually exclusive in NSCs, rarely occurring in the same cell. While 4EBP1/2 was phosphorylated in stem cells undergoing mitosis at the ventricular surface, S6 was phosphorylated in more differentiated cells migrating away from the ventricle. Phosphorylation of 4EBP1/2, but not S6, was responsive to quiescence induction in cultured embryonic NSCs. Further, inhibition of p-4EBP1/2, but not p-S6, was sufficient to induce quiescence. Collectively, this work offers new insight into the regulation of quiescence entry in embryonic NSCs and, thereby, correct patterning of the adult brain. These data suggest unique biological functions of specific posttranslational modifications and indicate that the preferential inhibition of such modifications may be a useful therapeutic approach in neurodevelopmental diseases where NSC numbers, proliferation, and differentiation are altered.
A thin line between conflict and reaction time effects on EEG and fMRI brain signals
Authors: Beldzik Ewa , Ullsperger Markus
Published: February 2023

The last two decades of electrophysiological and neuroimaging research converged that the activity in the medial frontal cortex plays a pivotal role in cognitive control processes. Notably, the midfrontal theta (MFT) oscillatory EEG power, as well as activity in the anterior midcingulate cortex (aMCC) or pre-supplementary motor area (preSMA), were consistently proclaimed as markers of conflict processing. However, these brain signals are strongly correlated with response time (RT) variability in various non-conflict tasks, which overshadows the true nature of their involvement. Our previous study (Beldzik et al., 2022) successfully identified these brain signals during a simultaneous EEG-fMRI experiment implementing Stroop and Simon tasks. Based on the assumption that overcoming the habitual prepotent response during high interference trials require additional neural resources beyond simple decision variable represented in RTs, here we aim to verify if these markers exhibit a congruency effect beyond RT variations. Furthermore, we explored if these brain signals represent either proactive or reactive cognitive control mechanisms by investigating two widely known behavioral phenomena observed in conflict tasks: proportion congruency and congruency sequence effects. The results revealed partially null findings for MFT activity, yet a distinct cognitive control specialization between aMCC and preSMA. Our study provides novel evidence that the former is involved in proactive control mechanisms, possibly contingency learning, whereas the latter reflects reactive control mechanisms by exhibiting a strong congruency effect regardless of RT variation and responding to adaptive behavior.
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

Electric 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

Accurate 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

Backgorund

RhoB 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.

Results

RhoB 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.

Conclusion

This 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

As 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

Microglia, 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

TheDrosophilaeye 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

Nervous 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

The 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

Understanding 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.

Importance

The 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

Learning 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

Deciphering 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

The 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

Epithelial-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

E-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.
Development and characterization of a multimeric recombinant protein based on the spike protein receptor binding domain of SARS-CoV-2 that can neutralize virus infection
Authors: de Lima Veronica Aparecida , da Silva Ferreira Rodrigo , Vilela Oliva Maria Luiza , Andreata-Santos Robert , Ramos Janini Luiz Mario , Maricato Juliana Terzi , Akamatsu Milena Apetito , Ho Paulo Lee , Schenkman Sergio
Published: February 2023

Background

The SARS-CoV-2 virus, responsible for the COVID-19 pandemic, has four structural proteins and sixteen non-structural proteins. The S-protein is one of the structural proteins exposed on the surface of the virus and is the main target for producing neutralizing antibodies and vaccines. The S-protein forms a trimer that can bind the angiotensin-converting enzyme 2 (ACE2) through its receptor binding domain (RBD) for cell entry.

Methods

We stably expressed in a constitutive manner in HEK293 cells a new recombinant protein containing a signal sequence of immunoglobulin to produce an extended C-terminal portion of the RBD followed by a region responsible for the trimerization inducer of the bacteriophage T4, and a sequence of 6 histidines. The protein was produced and released in the culture supernatant of cells and was purified by Ni-agarose column and exclusion chromatography. It was then characterized by SDS-polyacrylamide gel and used as antigen to generate protective antibodies to inhibit ACE2 receptor interaction and virus entry into Vero cells.

Results

The purified protein displayed a molecular mass of 135 kDa and with a secondary structure like the monomeric RBD. Electrophoresis analysis in SDS-polyacrylamide gel with and without reducing agents, and in the presence of crosslinkers indicated that it forms a multimeric structure composed of trimers and hexamers. The purified protein was able to bind the ACE2 receptor and generated high antibody titers in mice (1:10000), capable of inhibiting the binding of biotin labeled ACE2 to the virus S1 subunit, and to neutralize the entry of the SARS-CoV-2 Wuhan strain into cells.

Conclusion

Our results characterize a new multimeric protein based on S1 subunit to combat COVID-19, as a possible immunogen or antigen for diagnosis.
CRB3 navigates Rab11 trafficking vesicles to promote γTuRC assembly during ciliogenesis
Authors: Wang Bo , Liang Zheyong , tan Tan , Zhang Miao , Jiang Yina , Shang Yangyang , Gao Xiaoqian , Song Shaoran , Wang Ruiqi , Chen He , Liu Jie , Li Juan , Ren Yu , Liu Peijun
Published: February 2023

The primary cilium plays important roles in regulating cell differentiation, signal transduction, and tissue organization. Dysfunction of the primary cilium can lead to ciliopathies and cancer. The formation and organization of the primary cilium are highly associated with cell polarity proteins, such as the apical polarity protein CRB3. However, the molecular mechanisms by which CRB3 regulates ciliogenesis and the location of CRB3 remain unknown. Here, we show that CRB3, as a navigator, regulates vesicle trafficking in γ-TuRC assembly during ciliogenesis and cilium-related Hh and Wnt signaling pathways in tumorigenesis.Crb3knockout mice display severe defects of the primary cilium in the mammary ductal lumen and renal tubule, while mammary epithelial-specificCrb3knockout mice exhibit the promotion of ductal epithelial hyperplasia and tumorigenesis. CRB3 is essential for lumen formation and ciliary assembly in the mammary epithelium. We demonstrate that CRB3 localizes to the basal body and that CRB3 trafficking is mediated by Rab11-positive endosomes. Significantly, CRB3 interacts with Rab11 to navigate GCP6/Rab11 trafficking vesicles to CEP290, resulting in intact γ-TuRC assembly. In addition, CRB3-depleted cells are unresponsive to the activation of the Hh signaling pathway, while CRB3 regulates the Wnt signaling pathway. Therefore, our studies reveal the molecular mechanisms by which CRB3 recognizes Rab11-positive endosomes to facilitate ciliogenesis, and regulates cilium-related signaling pathways in tumorigenesis.
Scaling and controlling talent development in high-intensity organizations: the case of a Swedish football club
Authors: Carlsson-Wall Martin , DeMott Kai , Ali Hamza
Published: February 2023

Purpose

In this paper, the authors empirically and theoretically analyze the scaling and control of talent development to highlight an important part of commercialization in football clubs, especially in the light of a growing transfer market.

Design/methodology/approach

Conducting a single case study of a Swedish football club, the authors adapt a view of the club as a “high-intensity” organization (Alvesson and Kärreman, 2004), one that inherently relies on strong identification of employees and the fostering of talent. This view allows us to detail the importance of both socio-ideological and technocratic forms of control involved in the talent development process.

Findings

The authors show how socio-ideological and technocratic forms of control were combined to establish the football club as a “talent factory” in the league, as well as the corresponding challenges when scaling talent development activities and how these challenges were handled. In doing so, the authors contribute to the broader accounting literature on talent- and human resource management, as the authors provide an example of how football clubs may commercialize without necessarily violating their fundamental sports values.

Originality/value

Talent management has mainly been studied in terms of increasing player wages and a focus on the cost of talent. As opposed to these perspectives, the authors highlight the revenue potential in developing players in the light of a growing transfer market and the relevance of talent development for the commercialization of football clubs.
Latent topics identification from the articles of Sri Lankan authors using LDA
Authors: Ravikumar S. , Boruah Bidyut Bikash , Gayang Fullstar Lamin
Published: February 2023

Purpose

The purpose of the study is to identify the latent topics from 9102 Web of Science (WoS) indexed research articles published in 2645 journals of the Sri Lankan authors from 1989 to 2021 by applying Latent Dirichlet Allocation to the abstracts. Dominant topics in the corpus of text, the posterior probability of different terms in the topics and the publication proportions of the topics were discussed in the article.

Design/methodology/approach

Abstracts and other details of the studied articles are collected from WoS database by the authors. Data preprocessing is performed before the analysis. “ldatuning” from the R package is applied after preprocessing of text for deciding subjects in light of factual elements. Twenty topics are decided to extract as latent topics through four metrics methods.

Findings

It is observed that medical science, agriculture, research and development and chemistry-related topics dominate the subject categories as a whole. “Irrigation” and “mortality and health care” have a significant growth in the publication proportion from 2019 to 2021. For the most occurring latent topics, it is seen that terms like “activity” and “acid” carry higher posterior probability.

Practical implications

Topic models permit us to rapidly and efficiently address higher perspective inquiries without human mediation and are also helpful in information retrieval and document clustering. The unique feature of this study has highlighted how the growth of the universe of knowledge for a specific country can be studied using the LDA topic model.

Originality/value

This study will create an incentive for text analysis and information retrieval areas of research. The results of this paper gave an understanding of the writing development of the Sri Lankan authors in different subject spaces and over the period. Trends and intensity of publications from the Sri Lankan authors on different latent topics help to trace the interests and mostly practiced areas in different domains.
A bibliometric analysis and visualization of global research on rural livelihood
Authors: Khan Moin , Ahmad Ateeque , Yuvaraj Mayank , Husain Syed Shaz , Khan Daud
Published: February 2023

Purpose

This study aims to explore the scientific research progress in the field of “Rural Livelihood” from 1991 to 2022.

Design/methodology/approach

A total of 2,122 documents were extracted from the Web of Science Core Collection using the key terms “Rural Livelihood” OR “Rural Livelihoods” in the “Title-Abstract-Keyword” field. The statistical analysis was performed through VOSviewer, Bibliometrix, Biblioshiney open-source package of R language environment, and MS Office software.

Findings

The results show that the first research article related to the field of rural livelihood was published in 1991, and the rapid growth in the publications of rural livelihood was observed since 2000, with a positive annual growth rate of 14.87%. Shackleton CM (n = 30 articles) and Belcher B (n = 1235 citations) are the most productive and highly cited authors in the field of rural livelihood, respectively. World Development is the most prolific and dominant journal, followed by Sustainability and Land Use Policy. The citation analysis disclosed that “Capitals and capabilities: a framework for analysing peasant viability, rural livelihoods and poverty” is the most cited research paper published in the field of rural livelihood by Anthony Bebbington. University of Copenhagen, Wageningen University and Rhodes University emerged as the topmost organizations engaged in rural livelihood research. The USA and the UK are the most productive and cited countries in rural livelihood. The keyword analysis revealed that most of the research published in the field of rural livelihood has focussed on rural livelihoods, management, conservation, poverty, strategies, climate change, etc.; however, the least emphasis is given on the subjects like food security, income diversification, biodiversity, deforestation, soil fertility management, bio-economy and environmental intervention. The thematic evolution reflects that the field of rural livelihood has been extensively researched and has undergone many dimensions, such as agriculture, management, conservation, climate change, households, policy and biodiversity.

Originality/value

The study’s findings provide an insight into global research trends, latest advances, hot issues, leading topics, and the thematic evolution of rural livelihood research over the last 31 years approximately. This study is quite useful to researchers and stakeholders to obtain rigorous bibliographic knowledge on literature related to the topic and work accordingly for R&D activities.
Information literacy development and competencies of high school students in Accra
Authors: Kankam Philip Kwaku
Published: February 2023

Purpose

Information literacy (IL) is clearly important for academic performance, as evidenced by literature. It could be defined as a set of abilities, attitudes and experiences that enable people to recognize when they need information to solve an issue. The importance of investigating students’ IL competencies cannot be overstated. This study therefore aims to look into the IL development and competencies of high school students in Accra, as there appears to be a dearth of systematic study on this in Ghana.

Design/methodology/approach

To investigate this phenomenon, the study used a survey research design with a mixed-methods approach and a post-positivist research paradigm. A total of 454 high school students, 3 librarians and 3 heads of ICT departments from three senior high schools in Accra participated in this study. This study used two methods: an audit of the IL programmes and practices available at the selected schools as well as IL literacy assessment through the use of a standardized test instrument. The data collection tools used were a semi-structured interview schedule and a questionnaire.

Findings

This study found that high school students in Accra had low IL competencies. Again, the findings of this study revealed that inadequate infrastructure and lack of formalized IL instructions in schools hindered the IL development of students.

Originality/value

The author considers the study original both in conceptualization and design. The main question being interrogated stems from identified gaps in the literature and this study intends to fill these knowledge gaps. This study’s originality also stems from the fact that there is a paucity of information on the subject of study in the context of Ghana. This study recommends the need to integrate IL in the school curriculum to ensure effective and efficient IL instructions in high schools.