bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptome database forCamellia sinensisreveals genes important for flavonoid synthesis in tea plants
Authors: Zheng Xinghai , Mohd Ali Zahin , Lim Peng Ken , Mutwil Marek , Wang Yuefei 
Published: January 2024

AbstractTea, as one of the most popular beverages in the world, possesses a plethora of secondary metabolites that are beneficial to human health. Tea plants (Camellia sinensis) exhibit rich genetic diversity, where different cultivars can vary significantly in terms of yield, adaptability, morphology, and composition of secondary metabolites. Many tea cultivars have been the subject of much research interest, which have led to the accumulation of publicly available RNA-seq data. As such, it has become possible to systematically summarize the characteristics of different cultivars at the transcriptomic level, identify valuable functional genes, and infer gene functions through co-expression analysis. Here, the transcriptomes of 9 cultivars ofCamellia sinensiswere assembled and combined with the coding sequences of 13 cultivars ofCamellia sinensisto study the differences and similarities of gene expression and biological functions among cultivars. To give access to this data, we present TeaNekT (https://teanekt.sbs.ntu.edu.sg/), a web resource that provides user-friendly tools and interactive visualizations that facilitates the prediction of gene functions of various tea cultivars. We used TeaNekT to perform cross-cultivar comparison of co-expressed gene neighborhoods, clusters, and tissue-specific gene expression. We show that the members of the chalcone synthase (CHS) gene family, important for flavonoid synthesis, exhibit the highest expression variability, specific expression in leaves and buds, and significant modulation by methyl jasmonate (MeJA) treatment. By using comparative co-expression tools of TeaNekT, we identified multiple conserved genes involved in flavonoid biosynthesis among cultivars that have not been previously studied, warranting further research.
DCs targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors
Authors: López-Rodríguez Lucía , Morosi Luciano , La Terza Federica , Bourdely Pierre , Rospo Giuseppe , Amadio Roberto , Piperno Giulia Maria , Russo Valentina , Volponi Camilla , Vodret Simone , Joshi Sonal , Giannese Francesca , Lazarevi Dejan , Germano Giovanni , Stoitzner Patrizia , Bardelli Alberto , Dalod Marc , Pace Luigia , Caronni Nicoletta , Guermonprez Pierre , Benvenuti Federica 
Published: January 2024

AbstractCross-presentation by type 1 cDCs (cDC1) is critical to induce and sustain antitumoral CD8 T cell responses to model antigens, in various tumor settings. However, the impact of cross-presenting cDC1 and the potential of DC-based therapies in tumors carrying varied levels ofbona-fideneoantigens (neoAgs) remains unclear. Here we generated a non-small cell lung cancer model with distinct ranges of TMB and MHC-I neoepitopes to test immunogenicity and response to Flt3L+αCD40 (DC-therapy). We found that cDC1 are required to broaden the pattern of CD8 responses to basal and acquired neoAgs and DC-therapy strongly inhibits the growth of TMBhightumors. In contrast, TMBlowtumors induce weaker responses that are not sufficient to block progression. scRNA transcriptional analysis, immune profiling and functional assays show that DC-therapy triggers the accumulation of lung cDC1 with increased immunostimulatory properties and CD8 T cells with enhanced cytotoxic functions and reduced exhaustion, most prominently in neoAgshightumors. We conclude that boosting cDC1 activity is critical to broaden the diversity of anti-tumoral CD8 T cell responses and to leverage neoAgs content for therapeutic advantage.
Non-physiologic interaction of MG53 with insulin receptor and lack of evidence for MG53’s role in controlling insulin-stimulated Akt phosphorylation in muscle, heart and liver tissues
Authors: Lee Kyung Eun , Nishi Miyuki , Kim Jongsoo , Murayama Takashi , Dawson Zachary , Wang Xiaoliang , Zhou Xinyu , Tan Tao , Cai Chuanxi , Takeshima Hiroshi , Park Ki Ho 
Published: January 2024

ABSTRACTRationaleMG53’s known function in facilitating tissue repair and anti-inflammation has broad applications to regenerative medicine. There is controversy regarding MG53’s role in the development of type 2 diabetes mellitus (T2DM).ObjectiveThis study aims to address this controversy – whether MG53’s myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues.Study DesignWe determined the binding affinity of the recombinant human MG53 (rhMG53) to the insulin receptor extracellular domain (IR-ECD) and found low affinity of interaction with Kd(>480 nM). Using cultured C2C12 myotubes and HepG2 cells, we found no effect of rhMG53 on insulin-stimulated Akt phosphorylation (p-Akt). We performed in vivo assay with C57BL/6J mice subjected to insulin stimulation (1 U/kg, intraperitoneal injection) and observed no effect of rhMG53 on insulin-stimulated p-Akt in muscle, heart and liver tissues.ConclusionOverall, our data suggest that rhMG53 can bind to the IR-ECD, however has a low likelihood of a physiologic role, as the Kdfor binding is ∼10,000 higher than the physiologic level of MG53 present in the serum of rodents and humans (∼10 pM). Our findings question the notion proposed by Xiao and colleagues – whether targeting circulating MG53 opens a new therapeutic avenue for T2DM and its complications.
Identifying genomic data use with the Data Citation Explorer
Authors: Byers Neil , Parker Charles , Beecroft Chris , Reddy T.B.K. , Salamon Hugh , Garrity George , Fagnan Kjiersten 
Published: January 2024

ABSTRACTIncreases in sequencing capacity, combined with rapid accumulation of publications and associated data resources, have increased the complexity of maintaining associations between literature and genomic data. As the volume of literature and data have exceeded the capacity of manual curation, automated approaches to maintaining and confirming associations among these resources have become necessary. Here we present the Data Citation Explorer (DCE), which discovers literature incorporating genomic data whether or not provenance was clearly indicated. This service provides advantages over manual curation methods including consistent resource coverage, metadata enrichment, documentation of new use cases, and identification of conflicting metadata. The service reduces labor costs associated with manual review, improves the quality of genome metadata maintained by the U.S. Department of Energy Joint Genome Institute (JGI), and increases the number of known publications that incorporate its data products. The DCE facilitates an understanding of JGI impact, improves credit attribution for data generators, and can encourage data sharing by allowing scientists to see how reuse amplifies the impact of their original studies.
Deciphering the molecular mechanism underlying morphology transition in two-component DNA-protein cophase separation
Authors: Li Cheng , Bian Yunqiang , Tang Yiting , Meng Lingyu , Yin Peipei , Hong Ye , Cheng Jun , Li Yuchen , Lin Jie , Tang Chao , Chen Chunlai , Li Wenfei , Qi Zhi 
Published: January 2024

AbstractNucleic acid and protein co-condensates exhibit diverse morphologies crucial for fundamental cellular processes. Despite their significance, the molecular mechanisms governing morphology transitions remain poorly understood. To address this gap in knowledge, we investigated DNA and the human transcription factor p53 as a model system, specifically focusing on DNA-protein interactive co-condensates (DPICs)—a scenario where neither dsDNA nor the protein demonstrates phase-separation behavior individually. Through a combination of experimental assays and theoretical approaches, we elucidated: (i) the phase diagram of DPICs, identifying two distinct transition phenomena—a phase transition between viscoelastic fluid and viscoelastic solid states, and a morphology transition from droplet-like to "pearl chain"-like DPICs; (ii) the growth dynamics of DPICs. Droplet-like and "pearl chain"-like DPICs, although with dramatically distinct final morphologies and material properties, share a common initial critical microscopic cluster (CMC) size at the nanometer scale during the early stage of phase separation. These findings provide novel insights into the biophysical mechanisms underlying multi-component phase separations within cellular environments.Significance StatementNucleic acids and proteins have the capacity to form co-condensates, exhibiting various morphologies, including droplet-like and “pearl chains” formations. Despite this observation, the underlying biophysical mechanisms remain poorly understood. In this study, we employed DNA and the protein p53 as a model system. Our investigation revealed that the strength of the DNA-p53 interactions dictates the material properties of the co-condensates, leading to a transition from a viscoelastic fluid to a viscoelastic solid phase. This transition is accompanied by a morphological shift from droplet-like formations to structures resembling “pearl chains”. Additionally, we explored the growth dynamics of these co-condensates and demonstrated that the strength of p53-DNA interactions influences the relaxation time of the co-condensates, thereby potentially determining their morphological features.
Precision phenotyping of a barley diversity set reveals distinct drought response strategies
Authors: Paul Maitry , Dalal Ahan , Jääskeläinen Marko , Moshelion Menachem , Schulman Alan H. 
Published: January 2024

AbstractPlants exhibit a wide array of responses and adaptive mechanisms to drought. During drought, the trade-off between water loss and CO2uptake for growth is mediated by the regulation of stomatal aperture in response to soil water content (SWC), among other factors. We earlier identified, in a few reference varieties of barley that differed by the SWC at which transpiration was curtailed, two divergent water use strategies: water-saving (“isohydric”) and water-spending (“anisohydric”). We proposed that an isohydric strategy may reduce risk from early droughts in climates where the probability of precipitation increases during the growing season, whereas an anisohydric strategy is consistent with environments having terminal droughts, or with those where dry periods are short and show little seasonal variation. Here, we have examined drought response in an 81-line barley diversity set that spans 20thcentury European barley breeding and identified a several lines with a third, dynamic transpirational response to drought. We found a strong positive correlation between vigor and transpiration, the dynamic group being highest for both. However, these lines curtailed daily transpiration at a higher SWC than the isohydric group. While the dynamic lines, particularly cv Hydrogen and Baronesse, were not the most resilient in terms of restoring initial growth rates, their strong initial vigor and high return to initial transpiration rates meant that their growth nevertheless surpassed more resilient lines during recovery from drought. The results will be of use for defining barley physiological ideotypes suited to future climate scenarios.
3D Bioprinting of Collagen-based Microfluidics for Engineering Fully-biologic Tissue Systems
Authors: Shiwarski Daniel J. , Hudson Andrew R. , Tashman Joshua W. , Bakirci Ezgi , Moss Samuel , Coffin Brian D. , Feinberg Adam W. 
Published: January 2024

AbstractMicrofluidic and organ-on-a-chip devices have improved the physiologic and translational relevance of in vitro systems in applications ranging from disease modeling to drug discovery and pharmacology. However, current manufacturing approaches have limitations in terms of materials used, non-native mechanical properties, patterning of extracellular matrix (ECM) and cells in 3D, and remodeling by cells into more complex tissues. We present a method to 3D bioprint ECM and cells into microfluidic collagen-based high-resolution internally perfusable scaffolds (CHIPS) that address these limitations, expand design complexity, and simplify fabrication. Additionally, CHIPS enable size-dependent diffusion of molecules out of perfusable channels into the surrounding device to support cell migration and remodeling, formation of capillary-like networks, and integration of secretory cell types to form a glucose-responsive, insulin-secreting pancreatic-like microphysiological system.One-Sentence SummaryMulti-material FRESH 3D bioprinting of microfluidic CHIPS to generate fully biologic centimeter-scale and vascularized pancreatic-like tissue systems.
A learned score function improves the power of mass spectrometry database search
Authors: Ananth Varun , Sanders Justin , Yilmaz Melih , Oh Sewoong , Noble William Stafford 
Published: January 2024

AbstractOne of the core problems in the analysis of protein tandem mass spectrometry data is the peptide assignment problem: determining, for each observed spectrum, the peptide sequence that was responsible for generating the spectrum. Two primary classes of methods are used to solve this problem: database search andde novopeptide sequencing. State-of-the-art methods forde novosequencing employ machine learning methods, whereas most database search engines use hand-designed score functions to evaluate the quality of a match between an observed spectrum and a candidate peptide from the database. We hypothesize that machine learning models forde novosequencing implicitly learn a score function that captures the relationship between peptides and spectra, and thus may be re-purposed as a score function for database search. Because this score function is trained from massive amounts of mass spectrometry data, it could potentially outperform existing, hand-designed database search tools. To test this hypothesis, we re-engineered Casanovo, which has been shown to provide state-of-the-artde novosequencing capabilities, to assign scores to given peptide-spectrum pairs. We then evaluated the statistical power of this Casanovo score function, Casanovo-DB, to detect peptides on a benchmark of three mass spectrometry runs from three different species. Our results show that, at a 1% peptide-level false discovery rate threshold, Casanovo-DB outperforms existing hand-designed score functions by 35% to 88%. In addition, we show that re-scoring with the Percolator post-processor benefits Casanovo-DB more than other score functions, further increasing the number of detected peptides.
Decoding the Microbiome-Metabolome Nexus: A Systematic Benchmark of Integrative Strategies
Authors: Mangnier Loïc , Bodein Antoine , Mariaz Margaux , Scott-Boyer Marie-Pier , Mathieu Alban , Vashist Neerja , Bramble Matthew S. , Droit Arnaud 
Published: January 2024

AbstractBackgroundThe exponential growth of high-throughput sequencing technologies was an incredible opportunity for researchers to combine various -omics within computational frameworks. Among these, metagenomics and metabolomics data have gained an increasing interest due to their involvement in many complex diseases. However, currently, no standard seems to emerge for jointly integrating both microbiome and metabolome datasets within statistical models.ResultsThus, in this paper we comprehensively benchmarked nineteen different integrative methods to untangle the complex relationships between microorganisms and metabolites. Methods evaluated in this paper cover most of the researcher’s goals such as global associations, data summarization, individual associations, and feature selection. Through an extensive and realistic simulation we identified best methods across questions commonly encountered by researchers. We applied the most promising methods in an application to real gut microbial datasets, unraveling complementary biological processes involved between the two omics. We also provided practical guidelines for practitioners tailored to specific scientific questions and data types.ConclusionIn summary, our work paves the way toward establishing research standards when mutually analyzing metagenomics and metabolomics data, building foundations for future methodological developments.
Macrophage Polarizations in the Placenta and Lung are Associated with Bronchopulmonary Dysplasia
Authors: Mestan Karen K. , Sharma Abhineet , Lazar Sarah , Pandey Sonalisa , Parast Mana M. , Laurent Louise C. , Prince Lawrence S. , Sahoo Debashis 
Published: January 2024

ABSTRACTThe intricate interplay between macrophage polarization and placenta vascular dysfunction has garnered increasing attention in the context of placental inflammatory diseases. This study delves into the complex relationship between macrophage polarization within the placenta and its potential impact on the development of vascular dysfunction and inflammatory conditions. The placenta, a crucial organ in fetal development, relies on a finely tuned balance of immune responses for proper functioning. Disruptions in this delicate equilibrium can lead to pathological conditions, including inflammatory diseases affecting the fetus and newborn infant.We explored the interconnectedness between placental macrophage polarization and its relevance to lung macrophages, particularly in the context of early life lung development. Bronchopulmonary dysplasia (BPD), the most common chronic lung disease of prematurity, has been associated with abnormal immune responses, and understanding the role of macrophages in this context is pivotal. The investigation aims to shed light on how alterations in placental macrophage polarization may contribute to lung macrophage behavior and, consequently, influence the development of BPD. By unraveling the intricate mechanisms linking macrophage polarization, placental dysfunction and BPD, this research seeks to provide insights that could pave the way for targeted therapeutic interventions. The findings may offer novel perspectives on preventing and managing placental and lung-related pathologies, ultimately contributing to improved maternal and neonatal health outcomes.
TTSBBC: Triplex Target Site Biomarkers and Barcodes in Cancer
Authors: Ylagan Maya , Xu Qi , Kowalski Jeanne 
Published: January 2024

ABSTRACTThe technology of Triplex-forming oligonucleotides (TFOs) provides an approach to manipulate genes at the DNA level. TFOs bind to specific sites on genomic DNA, creating a unique intermolecular triple-helix DNA structure through Hoogsteen hydrogen bonding. This targeting by TFOs is site-specific and the locations TFOs bind are referred to as TFO target sites (TTS). Triplexes have been observed to selectively influence gene expression, homologous recombination, mutations, protein binding, and DNA damage. These sites typically feature a poly-purine sequence in duplex DNA, and the characteristics of these TTS sequences greatly influence the formation of the triplex. We introduce TTSBBC, a novel analysis and visualization platform designed to explore features of TTS sequences to enable users to design and validate TTSs. The web server can be freely accessed athttps://kowalski-labapps.dellmed.utexas.edu/TTSBC/.
Initial pig developmental stage influences intestinal organoid growth but not phenotype
Authors: Duchesne Camille , Randuineau Gwénaëlle , Normand Laurence Le , Romé Véronique , Laraqui Samia , Arnaud Alexis Pierre , Boudry Gaëlle 
Published: January 2024

AbstractIntestinal organoids are promising tools in the context of animal experiment reduction. Yet, a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig, a valuable model of Humans. Organoids were derived from jejunal and colonic ISC obtained from 1, 7, 28, 36 and 180-day old pigs and passaged three times. We first confirmed by qPCR that the expression of 18% of the >80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (P<0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, P<0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (P<0.05), spheroids were larger during the primary culture but smaller after two passages (P<0.05) and organoids smaller after one passage (P>0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) were observed between organoids originating from 7 or 180-day old pigs, while difference between intestinal site origin were noticed. In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence their phenotype.
Silver nanoparticles can be sampled by ultrafiltration probe but elution into & recovery from plasma and DPBS differsin vitro
Authors: Risselada Marije , McCain Robyn R , Bates Miriam G , Anderson Makensie L 
Published: January 2024

AbstractWe compared 1) the influence of elution fluid on rate, pattern, and completeness of silver nanoparticle (AgNP) elution, and 2) ultrafiltration (UF) probe and direct samplingin vitro. Six specimens (2.5ml of 0.02mg/ml 10nm AgNP and 5.0ml of 30% poloxamer 407) contained in a dialysis tube (12-14kDa pores) were placed in 100ml Dulbecco’s Phosphate Buffered Saline (DPBS) (n=3) or canine plasma (n=3) for 96h on a stirred hot plate (37°C and 600rpm) and sampled 20 times. Six pipette and UF probe samples were taken of a 0.001mg AgNP/ml DPBS or plasma solution. Inductively coupled plasma mass spectrometry was used to analyze Ag. Stock plasma contained Ag. At 96h, 5/6 dialysis tubes had not fully released AgNP. One peak in hourly Ag increase was present in DPBS (10-13h), and two peaks in plasma (6-8h and 10-13h). The hourly Ag increase in plasma decreased earlier than in DPBS. UF probe sampling was possible in both DPBS and plasma and resulted in higher Ag concentrations but with more variation than pipette samples. Whilein vitrouse of DPBS might be more cost effective, plasma should be considered due to difference in elution and recovery.