bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modernizing the original influenza vaccine to enhance protective antibody responses against neuraminidase antigens
Authors: Martinez Mira Rakic , Gao Jin , Wan Hongquan , Kang Hyeog , Klenow Laura , Daniels Robert 
Published: February 2023

ABSTRACTMost seasonal influenza vaccines are produced using hemagglutinin (HA) surface antigens from inactivated virions. However, virions are thought to be a suboptimal source for the less abundant NA surface antigen, which is also protective against severe disease. Here, we demonstrate that inactivated influenza virions are compatible with two modern approaches for improving protective NA antibody responses. Using a DBA/2J mouse model, we confirmed that the strong infection-induced NA inhibitory (NAI) antibody responses are only achieved by high dose immunizations of inactivated virions, likely due to low viral NA content. Based on this observation, we first produced virions with higher NA content by using reverse genetics to exchange the viral internal gene segments. Single immunizations with these inactivated virions enhanced NAI antibody responses, improved NA-based protection from a lethal viral challenge and allowed the development of natural immunity to the heterotypic challenge virus HA. Second, we combined inactivated virions with recombinant NA proteins. These mixtures increased NA-based protection following viral challenge and elicited stronger NA antibody responses than either component alone, especially when the NAs were homologous. Together, these results indicate that viral- and protein-based vaccines can be combined in a single syringe to improve protective antibody responses to influenza antigens.
Direct optical nanoscopy unveils signatures of cytokine-induced β-cell structural and functional stress
Authors: Pugliese Licia Anna , De Lorenzi Valentina , Bernardi Mario , Ghignoli Samuele , Tesi Marta , Marchetti Piero , Cardarelli Francesco , Pesce Luca 
Published: February 2023

AbstractHere we exploit a combination of advanced optical-microscopy tools and fluorescently-labeled molecular targets in rat Insulinoma 1E β-cells exposed to proinflammatory cytokines. Expansion microscopy (ExM) is used to achieve the spatial resolution (~50 nm) needed to analyze the structural features of key subcellular targets, i.e. insulin secretory granules (ISGs), microtubules, actin filaments, and mitochondria; time-lapse live-cell microscopy, on the other hand, provides complementary information on key dynamic and metabolic subcellular parameters. It is found that 24-hours exposure to proinflammatory cytokines induces a neat decrease in the number of ISGs and alteration in the dynamics of the residual pool, marked depolymerization of microtubules, change in mitochondrial morphology and metabolic activity, and decreased cell responsiveness to glucose stimulation. This is accompanied by clear signatures of the production of reactive oxygen species. Reported results provide direct evidence that proinflammatory cytokines act as potent stimulators of insulin secretion and, concomitantly, as cell stressors.
Integrated analysis and annotation for T-cell receptor sequences using TCRosetta
Authors: Yue Tao , Chen Si-Yi , Shen Wen-Kang , Cheng Liming , Guo An-Yuan 
Published: February 2023

AbstractBackgroundT cells and T cell receptors (TCRs) are essential components of the adaptive immune system. TCRs, on the surface of T cells, are responsible for recognizing and binding antigen peptide-MHC complex and play vital roles in T-cell immunology. Characterization of TCR repertoire offers a promising and high informative source for understanding the functions of T cells in immune responses and immunotherapies. Many researchers are now interested in TCR repertoire study; however, there are rare online servers for TCR analysis, especially no servers for TCR annotation and advanced analyses.ResultsWe developed TCRosetta, a comprehensive online server integrating the analytical methods for TCR repertoire/sequences analysis and visualization. TCRosetta combines general features analysis, large-scale sequence clustering, network construction, TCR-peptide binding prediction, generation probability calculation, and k-mer motif analysis for robust TCR sequence analysis, making TCR data analysis as simple as possible and allowing users to concentrate on research rather than coding. In addition, TCRosetta could annotate disease information for TRB CDR3 sequences by batch searching similar sequences in manually curated disease-related TCR database. The TCRosetta server accepts multiple input data formats and can analyze ∼20000 TCR sequences in less than three minutes.ConclusionsTCRosetta is the most comprehensive web server to date for TCR sequences/repertoires analysis and it is freely available athttp://bioinfo.life.hust.edu.cn/TCRosetta/. It can be applied to help discover novel biomarkers for disease diagnosis and identify cancer-associated TCR sequences.WHAT IS ALERADY KNOWN ON THIS TOPICT cell receptor repertoires are largely untapped resource than can be used for predicting immune responses to different exposures including viral infections and tumor neoantigens. The downstream analysis of TCR repertoire is often performed by different tools requiring diverse operating environments and expertise. There is no webserver for comprehensive TCR repertoire analysis including general and advanced analysis.WHAT THIS STUDY ADDSWe developed TCRosetta, a comprehensive platform for analyzing T-cell repertoire which combines nearly all TCR analysis methods. It supports different kinds of the format of input including most mainstream TCR extraction tools or amino acid sequences. It could analyze the features of TCR repertoire and display them in interactive graphs and is the first platform with a batch search and TCR annotation function.HOW THIS STUDY MIGHT AFFECT RESEARCH, PACTICE OR POLICYTCRosetta can be applied to discover novel biomarkers to predict response in immunotherapy such TCR repertoire diversity and clonality. It also can identify cancer-associated TCR sequences by clustering biochemically similar CDR3 sequences. It can make TCR repertoire analysis as effortless as possible and help users focus on research instead of coding.
Birds are easier to trick: an effect of magnetic field manipulation on migratory orientation of Nathusius’ pipistrelle in the circular release box
Authors: Cellarius Fyodor , Utvenko Gleb , Markovets Mikhail , Pakhomov Alexander 
Published: February 2023

SummaryBats, like birds, are capable of long annual migrations; however, a very limited number of studies are devoted to the role of the Earth’s magnetic field in bat navigation. We aimed to perform a series of experiments on Nathusius’ pipistrelle (Pipistrellus nathusii) to ensure that they are able to use the geomagnetic field for orientation. Bats were tested under two different conditions: in the geomagnetic field and the field, rotated 120° CW. To determine the takeoff direction and analyse behaviour in different magnetic conditions, we used the modified circular release box (CRBox) and a mini camera with IR LEDs. Helmholtz magnetic coils were used to manipulate the magnetic field. Bats were captured during migration through the Curonian spit (Kaliningrad region, Russia). Totally 53 bats were tested during August and September 2021-2022. During the second year, we recorded post-release bats’ behaviour using a thermal camera. Although results from 2021 are ambiguous, data obtained in 2022 suggests that under given conditions bats, unlike birds, could prefer local audible landmarks and wind direction prior to global cues. However, the recordings of released bats clearly show that they have some specific directional preferences, which correspond to their migratory orientation.
Antibody-mediated cell entry of SARS-CoV-2
Authors: Kibria Md Golam , Lavine Christy L. , Tang Weichun , Wang Shaowei , Gao Hailong , Shi Wei , Zhu Haisun , Voyer Jewel , Rits-Volloch Sophia , Keerti  , Bi Caihong , Peng Hanqin , Wesemann Duane R. , Lu Jianming , Xie Hang , Seaman Michael S. , Chen Bing 
Published: February 2023

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus-encoded spike protein and fusion between the viral and target cell membranes. We report here that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor-binding domain of the spike can replace ACE2 to serve as a receptor and efficiently support membrane fusion and viral infectivity. These receptor-like antibodies can function in the form of a complex of their soluble immunoglobulin G with Fc-gamma receptor I, a chimera of their antigen-binding fragment with the transmembrane domain of ACE2 or a membrane-bound B cell receptor, indicating that ACE2 and its specific interactions with the spike protein are dispensable for SARS-CoV-2 entry. These results suggest that antibody responses against SARS-CoV-2 may expand the viral tropism to otherwise nonpermissive cell types; they have important implications for viral transmission and pathogenesis.
A standardized and reproducible workflow for membrane glass slides in routine histology and spatial proteomics
Authors: Nordmann Thierry M. , Schweizer Lisa , Metousis Andreas , Thielert Marvin , Rodriguez Edwin , Rahbek-Gjerdrum Lise Mette , Stadler Pia-Charlotte , Bzorek Michael , Mund Andreas , Rosenberger Florian A. , Mann Matthias 
Published: February 2023

ABSTRACTDefining the molecular phenotype of single cellsin-situis essential for understanding tissue heterogeneity in health and disease. Powerful imaging technologies have recently been joined by spatial omics technologies, promising unparalleled insights into the molecular landscape of biological samples. One approach involves laser microdissection in combination with membrane glass slides for the isolation of single cells from specific anatomical regions for further analysis by spatial omics. However, so far this is not fully compatible with automated staining platforms and routine histology procedures such as heat-induced epitope retrieval, limiting reproducibility, throughput and integration of advanced staining procedures. This study describes a robust workflow for routine use of glass membrane slides, allowing precise extraction of tissue in combination with automated and multicolor immunofluorescence staining. The key advance is the addition of glycerol to standard heat-induced epitope retrieval protocol, preventing membrane distortion while preserving antigen retrieval properties. Importantly, we show that glycerol is fully compatible with mass-spectrometry based proteomics and does not affect proteome depth or quality. Further, we enable single focal plane imaging by removing remaining trapped air pockets with an incision. We demonstrate our workflow using the recently introduced Deep Visual Proteomics technology on the single-cell type analysis of adjacent suprabasal and basal keratinocytes of human skin. Our protocol extends the utility of membrane glass slides and enables much more robust integration with routine histology procedures, high-throughput multiplexed imaging and sophisticated downstream spatial omics technologies.
Cysteine-Rich Intestinal Protein 1 is a Novel Surface Marker for Myometrial Stem/Progenitor Cells
Authors: Paul Emmanuel N. , Carpenter Tyler J. , Fitch Sarah , Sheridan Rachael , Lau Kin H. , Arora Ripla , Teixeira Jose M. 
Published: February 2023

SummaryMyometrial stem/progenitor cells (MyoSPCs) have been proposed as the cells of origin for uterine fibroids, which are benign tumors that develop in the myometrium of most reproductive age women, but the identity of the MyoSPC has not been well established. We previously identified SUSD2 as a possible MyoSPC marker, but the relatively poor enrichment in stem cell characteristics of SUSD2+ over SUSD2- cells compelled us to find better discerning markers for more rigorous downstream analyses. We combined bulk RNA-seq of SUSD2+/- cells with single cell RNA-seq to identify markers capable of further enriching for MyoSPCs. We observed seven distinct cell clusters within the myometrium, with the vascular myocyte cluster most highly enriched for MyoSPC characteristics and markers, includingSUSD2. CRIP1expression was found highly upregulated in both techniques and was used as a marker to sort CRIP1+/PECAM1- cells that were both enriched for colony forming potential and able to differentiate into mesenchymal lineages, suggesting that CRIP1+/PECAM1- cells could be used to better study the etiology of uterine fibroids.
Recruitment of the SNX17-Retriever recycling pathway regulates synaptic function and plasticity
Authors: Rivero-Ríos Pilar , Tsukahara Takao , Uygun Tunahan , Chen Alex , Chavis Garrett D. , Giridharan Sai Srinivas Panapakkam , Iwase Shigeki , Sutton Michael A. , Weisman Lois S. 
Published: February 2023

AbstractTrafficking of cell-surface proteins from endosomes to the plasma membrane is a key mechanism to regulate synaptic function. In non-neuronal cells, proteins recycle to the plasma membrane either via the SNX27-Retromer-WASH pathway, or via the recently discovered SNX17-Retriever-CCC-WASH pathway. While SNX27 is responsible for the recycling of key neuronal receptors, the roles of SNX17 in neurons are less understood. Here, using cultured hippocampal neurons, we demonstrate that the SNX17 pathway regulates synaptic function and plasticity. Disruption of this pathway results in a loss of excitatory synapses and prevents structural plasticity during chemical long-term potentiation (cLTP). cLTP drives SNX17 recruitment to synapses, where its roles are in part mediated by regulating surface expression of β1-integrin. SNX17 recruitment relies on NMDAR activation, CamKII signaling, and requires binding to the Retriever and PI(3)P. Together, these findings provide molecular insights into the regulation of SNX17 at synapses, and define key roles for SNX17 in synaptic maintenance and in regulating enduring forms of synaptic plasticity.
Complex petal spot formation in the Beetle Daisy (Gorteria diffusa) relies on spot-specific accumulation of malonylated anthocyanin regulated by paralogous GdMYBSG6 transcription factors
Authors: Fattorini Róisín , Khojayori Farahnoz , Mellers Gregory , Moyroud Edwige , Serrano Eva Herrero , Kellenberger Roman T , Walker Rachel , Wang Qi , Hill Lionel , Glover Beverley J 
Published: February 2023

SummaryGorteria diffusahas elaborate petal spots that attract male bee-fly pollinators through sexual deception but the genetic basis ofG. diffusapetal spot development is currently unknown. Here we investigate the regulation of pigmentation during spot formation.We used UHPLC-MS/MS to determine the anthocyanin composition of spots and background pigmentation inG. diffusa. Combining gene expression analysis with protein interaction assays we characterised three R2R3-MYB genes regulating anthocyanin production inG. diffusaspots.We found that cyanidin 3-glucoside pigmentsG. diffusaray floret petals. Unlike other petal regions, spots contain a high proportion of malonylated anthocyanin. We identified three paralogous subgroup 6 R2R3-MYB transcription factors that activate the production of petal spot pigmentation. The corresponding genes are upregulated in developing spots and induce ectopic anthocyanin production upon heterologous expression in tobacco. EMSAs and dual luciferase assays suggest that these transcription factors regulate genes encoding three anthocyanin synthesis enzymes: anthocyanidin synthase (GdANS), dihydroflavonol reductase (GdDFR) and malonyl transferase (GdMAT1), accounting for the spot-specific production of malonylated pigments.Here we provide the first molecular characterisation ofG. diffusaspot development, showing that the elaboration of complex spots begins with accumulation of malonylated pigments at the base of ray floret petals, positively regulated by three subgroup 6 R2R3-MYB transcription factors.
A discrete choice experiment on oral and injection treatment preferences among moderate‐to‐severe psoriasis patients in Japan
Authors: Komine Mayumi , Kim Hyunchung , Yi Jingbo , Zhong Yichen , Sakai Yoko , Crawford Bruce , Habiro Katsuyoshi , Hikichi Yusuke , Feldman Steven R. 
Published: February 2023

AbstractLong‐term psoriasis (PsO) management remains challenging. With growing variation in treatment efficacy, cost, and modes of administration, patient preferences for different treatment characteristics are not well understood. A discrete choice experiment (DCE), informed by qualitative patient interviews, was conducted to assess patient preferences for different attributes of PsO treatments; 222 adult patients with moderate‐to‐severe PsO receiving systemic therapy participated in the DCE web survey. Better long‐term efficacy and lower cost were preferred (preference weights p < 0.05). Long‐term efficacy had the highest relative importance (RI) and mode of administration was as important as the outcome attributes (efficacy and safety). Patients also preferred oral to injectable administration. In subgroup analyses by disease severity, residence, psoriatic arthritis as a comorbidity, and gender, the trends for each subgroup were the same as the overall population although the extent of RI for administration mode varied. Mode of administration was more important for patients with moderate versus severe disease, or rural versus urban residence. This DCE utilized attributes related to both oral and injectable treatment as well as a broad study population of systemic treatment users. Preferences were further stratified by patient characteristics to explore trends in different subgroups. Understanding the RI of treatment attributes and the attribute trade‐offs acceptable to patients helps inform moderate‐to‐severe PsO systemic treatments decisions.
Strain‐specific quorum‐sensing responses determine virulence properties in Vibrio anguillarum
Authors: Mauritzen Jesper Juel , Søndberg Emilie , Kalatzis Panos G. , Roager Line , Gram Lone , Svenningsen Sine Lo , Middelboe Mathias 
Published: February 2023

AbstractBacterial populations communicate using quorum‐sensing (QS) molecules and switch on QS regulation to engage in coordinated behaviour such as biofilm formation or virulence. The marine fish pathogen Vibrio anguillarum harbours several QS systems, and our understanding of its QS regulation is still fragmentary. Here, we identify the VanT‐QS regulon and explore the diversity and trajectory of traits under QS regulation in Vibrio anguillarum through comparative transcriptomics of two wildtype strains and their corresponding mutants artificially locked in QS‐on (ΔvanO) or QS‐off (ΔvanT) states. Intriguingly, the two wildtype populations showed different QS responses to cell density changes and operated primarily in the QS‐on and QS‐off spectrum, respectively. Examining 27 V. anguillarum strains revealed that ~11% were QS‐negative, and GFP‐reporter measurements of nine QS‐positive strains revealed a highly strain‐specific nature of the QS responses. We showed that QS controls a plethora of genes involved in processes such as central metabolism, biofilm formation, competence, T6SS, and virulence properties in V. anguillarum, with large strain‐specific differences. Moreover, we demonstrated that the QS state is an important driver of virulence towards fish larvae in one of two V. anguillarum strains. We speculate that infections by mixed‐strain communities spanning diverse QS strategies optimize the infection efficiency of the pathogen.
The pragmatism of continual failure: environmental policy as experimentation in China
Authors: Bruckermann Charlotte 
Published: February 2023

AbstractFaced with stifling levels of airborne pollution, Chinese citizens hold the state accountable, demanding solutions through effective environmental policy. To reduce emissions, the state has set up experimental pilot carbon markets, where potential failure is cast as integral to continuing improvement. Those in charge of conceptualizing and implementing these experiments, namely carbon bureaucrats, consultants, and developers, feel their public responsibility acutely, sharpened by personal anxieties about pollution and health. But they also often perceive these carbon markets as doomed to fail, in absolute terms, in delivering decarbonization goals. Those charged with realizing carbon markets are therefore caught between, on the one hand, policy failure being folded into continual, pragmatic experimentation and, on the other, their embodied knowledge that such progressive, positively freighted failure is in fact terminal.
Stalinist political spectacle and the defeat of the opposition: The Fifteenth Congress of the Soviet Communist Party in 1927
Authors: TAKIGUCHI JUNYA 
Published: February 2023

AbstractThe Fifteenth Party Congress of the All‐Union Communist Party (Bolsheviks) took place in December 1927. It brought to an end the inner‐Party struggle of the Soviet Communist Party by confirming the expulsion of Leon Trotsky, Gregorii Zinoviev and other oppositionists from Party and government posts. The Fifteenth Party Congress marked the domination of Iosif Stalin and his allies over the whole Party and the beginning of Stalinist politics which flourished in the following decades. Despite extensive scholarly interest in this crucial Party congress in the history of the early Soviet Union and the Soviet Communist Party, little has been studied on the organisational aspect of the Fifteenth Congress. This article examines the process of establishing the organisational and institutional mechanisms ahead of the Fifteenth Congress, which enabled Stalin and the Central Committee to unanimously affirm the correctness of the Party line. It also explores how Stalin attained legitimacy as the Party leader during the pre‐Fifteenth Congress discussion and how it was presented at the Fifteenth Congress. Furthermore, this article demonstrates how the ‘memory’ of the Fifteenth Congress was constructed and how the Party leaders institutionalised the meaning of the Fifteenth Congress. Through these examinations, this article will shed fresh light on the Fifteenth Congress of the Soviet Communist Party and will contribute to the study of the rise of Stalinism.