bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment
Authors: Soupir Alex C , Hayes Mitchell T , Peak Taylor C , Ospina Oscar , Chakiryan Nicholas H , Berglund Anders E , Stewart Paul A , Nguyen Jonathan , Segura Carlos Moran , Francis Natasha L. , Echevarria Paola M. Ramos , Chahoud Jad , Li Roger , Tsai Kenneth Y. , Balasi Jodi A. , Peres Yamila Caraballo , Dhillon Jasreman , Martinez Lindsey A. , Gloria Warren E. , Schurman Nathan , Kim Sean , Gregory Mark , Mulé James , Fridley Brooke L , Manley Brandon J 
Published: November 2023

AbstractBackgroundImmunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples. Spatial gene set enrichment analysis (GSEA) and autocorrelation (coupling with high expression) of ligand-receptor transcript pairs were assessed. Multiplex immunofluorescence (mIF) validation was used for significant autocorrelative findings and the cancer genome atlas (TCGA) and the clinical proteomic tumor analysis consortium (CPTAC) databases were queried to assess bulk RNA expression and proteomic correlates.Results21 patient samples underwent SMI. Viable tumors following IO harbored more stromal CD8+ T cells and neutrophils than IO naïve tumors.YES1was significantly upregulated in IO exposed tumor cells. The epithelial-mesenchymal transition pathway was enriched on spatial GSEA and the associated transcript pairCOL4A1-ITGAVhad significantly higher autocorrelation in the stroma. Fibroblasts, tumor cells, and endothelium had the relative highest expression. More integrin αV+ cells were seen in IO exposed stroma on mIF validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of bothCOL4A1andITGAV. In CPTAC, collagen IV protein was more abundant in advanced stages of disease.ConclusionsOn spatial transcriptomics,COL4A1andITGAVwere more autocorrelated in IO-exposed stroma compared to IO-naïve tumors, with high expression amongst fibroblasts, tumor cells, and endothelium. Integrin represents a potential therapeutic target in IO treated ccRCC.
Video diffusion for early cellular apoptosis forecasting
Authors: Awasthi Akash , Nizam Jaer , Zare Samira , Ahmad Safwan , Montalvo Melisa J. , Varadarajan Navin , Roysam Badri , Nguyen Hien 
Published: November 2023

ABSTRACTReliable and early prediction of cell death (apoptosis) is critically important in various areas of biology, particularly in characterizing the effectiveness of cell-based infusion products utilized for cancer immunotherapy. While deep Convolutional Neural Networks (CNNs) are often used in state-of-the-art approaches for apoptosis classification, they typically focus solely on individual cells and ignore cell-cell interaction. To address this limitation, we propose a novel generative approach based on a video diffusion model, which predicts future cellular behaviors for early detection of apoptosis events, even before molecular markers like Annexin-V or visual indications like membrane blebbing become apparent. Our approach accounts for the interactions of multiple target cells and their spatial and temporal relationships at each time frame. We condition our generative model on two starting frames and utilize an auto-regressive framework to predict the subsequent five frames. Our model achieves a 0.88 F1 score on the cell death event classification and 2.11 mean absolute death-time error, significantly outperforming state-of-the-art methods.
Identification ofavaCfrom infant gut microbial isolates that convert 5AVA to 2-piperidone with high efficiency
Authors: Zhou Qiudi , Feng Lihui 
Published: November 2023

Abstract2-Piperidone has been identified as a biomarker for various human diseases, but its originin vivoremains poorly understood. Furthermore, 2-piperidone is a crucial industrial raw material, and thus the discovery of novel efficient 2-piperidone synthases may have an important application in its biosynthesis. In this study, we aimed to identify the bacterial source and metabolic mechanism of 2-piperidone from a previously generated infant gut microbial culture collection. We found that 2-piperidone could be produced from 5AVA by four bacterial strains, includingCollinsella aerofaciensLFYP39,Collinsella intestinalisLFYP54,Clostridium bolteaeLFYP116, andClostridium hathewayiLFYP18 from 51 bacterial strains. Furthermore, 2-piperidone could be synthesized from proline by cross-feeding betweenClostridium difficileLFYP43 andCollinsella intestinalisLFYP54. We employed a gain-of-function library to identify the geneavaC(5-aminovaleric acid cyclase) which can catalyze 5AVA to produce 2-piperidone inC. intestinalisLFYP54. Homologous genes ofavaCwere also identified and validated in the other three bacterial strains. GeneavaCexhibits a broad distribution in the natural environmental bacteria. Overall, our research identified the gut bacterial strains and the genes that are responsible for the production of 2-piperidone. This study may facilitate the prediction of 2-piperidone-related disease risks through the analysis of gut bacterial community composition, and enhance the efficiency of 2-piperidone in its biosynthesis in industry.ImportanceIn recent decades, it has become a consensus that gut microbiota can affect host health through producing metabolites. However, the complexity of gut flora composition makes finding the sources of the particular metabolite challenging. 2-piperidone is a biomarker for various diseases and a highly valued raw material for nylons. In this study, we identified the gut bacterial strains that can transform 5AVA to 2-piperidone. A novel 2-piperidone synthase gene,avaC, was also identified and characterized. These findings provided new insights into the potential connection between 2-piperidone related diseases and the intestinal flora, as well as a possible novel approach for more efficient biosynthesis of 2-piperidone in industry.
The T Cell Receptor β Chain Repertoire of Tumor Infiltrating Lymphocytes Improves Neoantigen Prediction and Prioritization
Authors: Pham Thi Mong Quynh , Nguyen Thanh Nhan , Nguyen Bui Que Tran , Tran Thi Phuong Diem , Pham Nguyen My Diem , Nguyen Hoang Thien Phuc , Ho Thi Kim Cuong , Nguyen Dinh Viet Linh , Nguyen Huu Thinh , Tran Duc Huy , Tran Thanh Sang , Pham Truong-Vinh Ngoc , Le Minh-Triet , Nguyen Thi Tuong Vy , Phan Minh-Duy , Giang Hoa , Nguyen Hoai-Nghia , Tran Le Son 
Published: November 2023

ABSTRACTIn the realm of cancer immunotherapy, the meticulous selection of neoantigens plays a fundamental role in enhancing personalized treatments. Traditionally, this selection process has heavily relied on predicting the binding of peptides to human leukocyte antigens (pHLA). Nevertheless, this approach often overlooks the dynamic interaction between tumor cells and the immune system. In response to this limitation, we have developed an innovative prediction algorithm rooted in machine learning, integrating T cell receptor β chain (TCRβ) profiling data from colorectal cancer (CRC) patients for a more precise neoantigen prioritization. TCRβ sequencing was conducted to profile the TCR repertoire of tumor-infiltrating lymphocytes (TILs) from 28 CRC patients. The data unveiled both intra-tumor and inter-patient heterogeneity in the TCRβ repertoires of CRC patients, likely resulting from the stochastic utilization of V and J segments in response to neoantigens. Our novel combined model integrates pHLA binding information with pHLA-TCR binding to prioritize neoantigens, resulting in heightened specificity and sensitivity compared to models using individual features alone. The efficacy of our proposed model was corroborated through ELISpot assays on long peptides, performed on four CRC patients. These assays demonstrated that neoantigen candidates prioritized by our combined model outperformed predictions made by the established tool NetMHCpan. This comprehensive assessment underscores the significance of integrating pHLA binding with pHLA-TCR binding analysis for more effective immunotherapeutic strategies.
Phylogenomics and phylodynamics of Zika Virus from Asia
Authors: Baig Kamil , Farah Shazia , Atkulwar Ashwin 
Published: November 2023

AbstractThe current study analyzes the Zika virus from Asia from a phylogenomic and phylodynamic perspective. To perform this study, 68 genomes from Asia were analyzed. A similar dataset was used to perform phylogenomics using Median Joining Network (MJN). MJN reconfirms African origin of Zika virus along with few notable instances of common origin of infection in some Asian countries. We investigated population dynamics using SkyGrid, Exponential Growth, and Constant Coalescence models. According to our phylodynamic analysis, effective population sizes throughout Asia reached higher peaks during the outbreak of 2016-2017. Zika virus population size increased exponentially during 2016-2017. From 1966 to 2021, there was a high and low peak in effective population size except for the outbreak of 2016-2017. To counter the outbreak of Zika Virus in Asian Countries in future, we recommend continuous genomic surveillance.
The stress history of soil bacteria under organic farming enhances the growth of wheat seedlings
Authors: Ornik Muriel , Salinas Renata , Antonacci Giona , Schädler Martin , Azarbad Hamed 
Published: November 2023

AbstractThe effects of stress factors associated with climate change and agricultural management practices on microorganisms are often studied separately, and it remains to be determined how these factors impact the soil microbiome and, subsequently, plant growth characteristics. The aim of this study was to understand how the historical climate and agriculture to which soil microbes have been exposed can influence the growth characteristics of wheat seedlings and their associated bacterial communities. We collected soil from organic and conventional fields with different histories of climate conditions to extract microbes to inoculate wheat seeds. The results showed a positive interaction between conventional farming practices and an ambient climate for faster and higher germination rates. We demonstrate that soil microbial extracts from organic farming with experience of the future climate significantly enhanced above-ground biomass along with bacterial diversity in the seedlings compared to the soil from conventional farming. Our data suggest that soil microbiomes selected by organic farming with a history of future climates can positively impact the aboveground biomass of wheat seedlings and their bacterial assemblages, emphasizing the potential benefits of organic farming practices under changing climate conditions.
Plant-based natural products for symptomatic relief of Parkinson’s disease: prevalence, interest, awareness and determinants
Authors: Diadhiou Sandra , Maas Bart R. , Schootemeijer Sabine , Bloem Bastiaan R. , de Vries Nienke M. , Calon Frédéric , Darweesh Sirwan K.L. , de Rus Jacquet Aurelie 
Published: November 2023

AbstractNatural health products (NHP) have emerged as a potential symptomatic therapeutic approach for persons with Parkinson’s disease (PwP). The objective of this study was to quantify the prevalence of ever use of NHP, interest in plant-based NHP, awareness of potential herb-drug interactions, and how often NHP use was discussed by PwP with their healthcare professionals. We addressed these objectives by embedding a cross-sectional 4-item survey within a large population-based cohort of PwP (PRIME-NL study). Sixty-five percent (n=367) of the 566 participants who were contacted completed the survey. Of those participants, 132 (36%) reported having used NHP to alleviate Parkinson’s disease (PD)-related symptoms, with coffee, cannabis and turmeric being the most popular. Overall, 12% (n=44) of PwP had used at least one NHP other than coffee or cannabis. Furthermore, 71% (n=259) participants expressed an interest in exploring the use of NHP, but only 39% (n=51) of NHP users were aware that these products could interact with PD medication. Finally, only 39% (n=51) of NHP users had discussed the use of NHP with their neurologist or PD nurse specialist. In a sensitivity analysis, we conservatively assumed that all non-responders to the survey had never used NHP and had no interest in exploring NHP. This rendered an estimated prevalence of NHP use of 23% and an estimated interest in exploring NHP of 46%. In conclusion, over one in three PwP has used NHP to alleviate symptoms of PD and the majority of PwP is interested in exploring the use of plant-based NHP. Most users had not discussed the intake of NHP with their PD healthcare professional and were unaware that these products could interact with PD medication. This study supports the need for evidence-based research on the properties of plant-derived therapeutics.
Enhancer landscape of lung neuroendocrine tumors reveals regulatory and developmental signatures with potential theranostic implications
Authors: Davis Ester , Avniel-Polak Shani , Abu-Kamel Shahd , Antman Israel , Saadoun Tsipora , Brim Chava , Bel-Ange Anat , Atlan Karine , Tzur Tomer , Akar Firas Abu , Wald Ori , Izhar Uzi , Hecht Merav , Grozinsky-Glasberg Simona , Drier Yotam 
Published: November 2023

AbstractWell-differentiated low-grade lung neuroendocrine tumors (lung carcinoids or LNETs) are histopathologically classified as typical and atypical LNETs, but each subtype is still heterogeneous at both the molecular level and its clinical manifestation. Here, we report the first genome-wide profiles of primary LNETs cis-regulatory elements by H3K27ac ChIP-seq with matching RNA-seq profiles. Analysis of these regulatory landscapes revealed three regulatory subtypes, independent of the typical / atypical classification. We identified unique differentiation signals that delineate each subtype. The ‘proneuronal subtype’ emerges under the influence of ASCL1, TCF4, and SOX4 transcription factors, embodying a pronounced proneuronal signature. The ‘luminal subtype’ is characterized by gain of acetylation at markers of luminal cells and GATA2 activation, and loss of LRP5 and OTP. The ‘HNF+ subtype’ is characterized by a robust enhancer landscape driven by HNF1A, HNF4A, and FOXA3, with a notable acetylation and expression of FGF signaling genes, especially FGFR3 and FGFR4 genes, pivotal components of the FGF pathway. Our findings not only deepen the understanding of LNETs’ regulatory and developmental diversity but also spotlight the HNF+ subtype’s reliance on FGFR signaling. We demonstrate that targeting this pathway with FGF inhibitors curtails tumor growth both in vitro and in xenograft models, unveiling a potential vulnerability and paving the way for targeted therapies. Overall, our work provides an important resource for studying LNETs to uncover regulatory networks, differentiation signals and therapeutically relevant dependences.
Pooled optical screening in bacteria using chromosomally expressed barcodes
Authors: Soares Ruben R. G. , García-Soriano Daniela A. , Larsson Jimmy , Fange David , Schirman Dvir , Grillo Marco , Knöppel Anna , Sen Beer Chakra , Svahn Fabian , Zikrin Spartak , Nilsson Mats , Elf Johan 
Published: November 2023

AbstractOptical pooled screening is an important tool to study dynamic phenotypes for libraries of genetically engineered cells. However, the desired engineering often requires that the barcodes used forin situgenotyping are expressed from the chromosome. This has not been possible in bacteria. Here we describe a method forin situgenotyping of libraries with genomic barcodes inEscherichia. coli. The method is applied to measure the intracellular maturation time of 81 red fluorescent proteins.
Co-habiting ants and silverfish display a converging feeding ecology
Authors: Parmentier Thomas , Molero-Baltanás Rafael , Valdivia Catalina , Gaju-Ricart Miquel , Boeckx Pascal , Łukasik Piotr , Wybouw Nicky 
Published: November 2023

AbstractSpecies from a great number of animal taxa have specialized to living with social hosts. Depending on their level of specialization, these symbiotic animals are characterized by distinct behavioural, chemical, and morphological traits that enable close heterospecific interactions. Despite its functional importance, our understanding of the feeding ecology of specialized animals living with social hosts remains limited.In this study, we examined how host specialization of silverfish co-habiting with ants affects several components of their feeding ecology. We combined stable isotope profiling, feeding assays, phylogenetic reconstruction, and microbial community characterization of theNeoasterolepismasilverfish genus and a wider nicoletiid and lepismatid silverfish panel where divergent myrmecophilous lifestyles are observed.Stable isotope profiling (δ13C and δ15N) showed that the isotopic niches (proxy for trophic niches) of granivorousMessorants andMessor-specializedNeoasterolepismaexhibit a remarkable overlap within an ant nest. Trophic experiments and gut dissections further supported that these specializedNeoasterolepismasilverfish transitioned to a diet that includes plant seeds. In contrast, the isotopic niches of generalistNeoasterolepismasilverfish and generalist nicoletiid silverfish were clearly different from their ant hosts within the shared nest environment.The impact of the myrmecophilous lifestyle on feeding ecology was also evident in the internal silverfish microbiome. Compared to generalists,Messor-specialists exhibited a higher bacterial density and a higher proportion of heterofermentative lactic acid bacteria. Moreover, the nest environment explained the infection profile (or the 16S rRNA genotypes) ofWeissellabacteria inMessor-specialized silverfish and the ant hosts.Together, we show that social hosts are important determinants for the feeding ecology of symbiotic animals, and can induce diet convergence.
Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice
Authors: Brito David V.C. , Kupke Janina , Sokolov Rostilav , Cambridge Sidney , Both Martin , Bengtson C. Peter , Rozov Andrei , Oliveira Ana M.M. 
Published: November 2023

AbstractLong-term memories are believed to be encoded by unique transcriptional signatures in the brain. The expression of immediate early genes (IEG) promotes structural and molecular changes required for memory consolidation. Recent evidence has shown that the brain is equipped with mechanisms that not only promote, but actively constrict memory formation. However, it remains unknown whether IEG expression may play a role in memory suppression. Here we uncovered a novel function of the IEG neuronal PAS domain protein 4 (Npas4), as an inducible memory suppressor gene of highly salient aversive experiences. Using a contextual fear conditioning paradigm, we found that low stimulus salience leads to monophasic Npas4 expression, while highly salient learning induces a biphasic expression of Npas4 in the hippocampus. The later phase requires NMDA receptor activity and is independent of dopaminergic neurotransmission. Ourin vivopharmacological and genetic manipulation experiments suggested that the later phase of Npas4 expression restricts the consolidation of a fear memory and promote behavioral flexibility, by facilitating fear extinction and the contextual specificity of fear responses. Moreover, immunofluorescence and electrophysiological analysis revealed a concomitant increase in synaptic input from cholecystokinin (CCK)-expressing interneurons. Our results demonstrate how salient experiences evoke unique temporal patterns of IEG expression that fine-tune memory consolidation. Moreover, our study provides evidence for inducible gene expression associated with memory suppression as a possible mechanism to balance the consolidation of highly salient memories, and thereby to evade the formation of maladaptive behavior.
Individual recognition in a jumping spider (Phidippus regius)
Authors: Dahl Christoph D. , Cheng Yaling 
Published: November 2023

SummaryIndividual recognition is conceptually complex and computationally intense, leading to the general assumption that this social knowledge is solely present in vertebrates with larger brains, while miniature-brained animals in differentiating societies eschew the evolutionary pressure for individual recognition by evolving computationally less demanding class-level recognition, such as kin, social rank, or mate recognition. Arguably, this social knowledge is restricted to species with a degree of sociality (sensu [1], for a review [2]). Here we show the exception to this rule in an asocial arthropod species, the jumping spider (Phidippus regius). Using a habituation - dishabituation paradigm, we visually confronted pairs of spatially separated spiders with each other and measured the ‘interest’ of one spider towards the other. The spiders exhibited high interest upon initial encounter of an individual, reflected in mutual approach behaviour, but adapted towards that individual when it reoccurred in the subsequent trial, indicated by their preference of staying farther apart. In contrast, spiders exhibited a rebound from habituation, reflected in mutual approach behaviour, when a different individual occurred in the subsequent trial, indicating the ability to tell apart spiders’ identities. These results suggest thatP. regiusis capable of individual recognition based on long-term social memory.
Understanding food pleasure in organic consumption: the moderating effects of trust within the theory of planned behavior
Authors: Cao Dayu , Zheng Yan , Li Gucheng 
Published: November 2023

PurposeThis study aims to identify and describe the relationships among sensory-driven pleasure, cognition-driven pleasure, symbolic-driven pleasure and organic food purchase behavior considering the moderating effects of functionality trust and authenticity trust from the viewpoint of the theory of planned behavior (TPB).Design/methodology/approachData were collected using a structured questionnaire survey in first-tier cities in China. A total of 352 consumers of organic foods participated in the study. Structural equation modeling and hierarchical regression analysis were employed for data analysis.FindingsThe results indicated the significant association of perceived behavioral control, subjective norm, attitude, sensory-driven pleasure and cognition-driven pleasure with purchase intention. Perceived behavioral control and purchase intention had significantly positive effects on purchase behavior. Moreover, functionality trust had a positive moderating effect on purchase intention and purchase behavior.Practical implicationsThis study not only provides novel and original insights for understanding organic consumption but also provides a reference for organic producers, sellers and policymakers to develop effective strategies to guide organic consumption that are conducive to promoting sustainable consumption.Originality/valueFor the first time, this research introduces the construct of food pleasure into the TPB to explore the relationships between food pleasure and purchase behavior based on the TPB. It may expand the scope of the TPB and provide valuable insights regarding how to improve the existing intention–behavior gap in organic consumption.