bluuebunny/crossref_metadata_2025_split huggingface dataset:
Raman spectroscopy reveals phenotype switches in breast cancer metastasis
Authors: Paidi Santosh Kumar , Troncoso Joel Rodriguez , Harper Mason G. , Liu Zhenhui , Nguyen Khue G. , Ravindranathan Sruthi , Ivers Jesse D. , Zaharoff David A. , Rajaram Narasimhan , Barman Ishan 
Published: June 2021

AbstractThe accurate analytical characterization of metastatic phenotype at primary tumor diagnosis and its evolution with time are critical for controlling metastatic progression of cancer. Here, we report a label-free optical strategy using Raman spectroscopy and machine learning to identify distinct metastatic phenotypes observed in tumors formed by isogenic murine breast cancer cell lines of progressively increasing metastatic propensities. Our Raman spectra-based random forest analysis provided evidence that machine learning models built on spectral data can allow the accurate identification of metastatic phenotype of independent test tumors. By silencing genes critical for metastasis in highly metastatic cell lines, we showed that the random forest classifiers provided predictions consistent with the observed phenotypic switch of the resultant tumors towards lower metastatic potential. Furthermore, the spectral assessment of lipid and collagen content of these tumors was consistent with the observed phenotypic switch. Overall, our findings indicate that Raman spectroscopy may offer a novel strategy to evaluate metastatic risk during primary tumor biopsies in clinical patients.
Modelling brain representations of abstract concepts
Authors: Kaiser Daniel , Jacobs Arthur M. , Cichy Radoslaw M. 
Published: June 2021

AbstractAbstract conceptual representations are critical for human cognition. Despite their importance, key properties of these representations remain poorly understood. Here, we used computational models of distributional semantics to predict multivariate fMRI activity patterns during the activation and contextualization of abstract concepts. We devised a task in which participants had to embed abstract nouns into a story that they developed around a given background context. We found that representations in inferior parietal cortex were predicted by concept similarities emerging in models of distributional semantics. By constructing different model families, we reveal the models’ learning trajectories and delineate how abstract and concrete training materials contribute to the formation of brain-like representations. These results inform theories about the format and emergence of abstract conceptual representations in the human brain.
Partial genome assembly of the medicinal plantEphedra sinica
Authors: Li Qiushi , Morris Jeremy S. , Facchini Peter J. , Yeaman Sam 
Published: June 2021

AbstractEphedra sinicais a high-value medicinal plant that produces important phenylpropylamino alkaloids pseudoephedrine and ephedrine. Few genomics resources exist forE. sinica, which has been characterized as a tetraploid with a monoploid genome size of 8.56 Gb. Here we reported a partial genome assembly ofE. sinica(12.8 Gb) based on Illumina short-read sequencing at low coverage.
The human ribosomal RNA gene is composed of highly homogenized tandem clusters
Authors: Hori Yutaro , Shimamoto Akira , Kobayashi Takehiko 
Published: June 2021

ABSTRACTThe structure of the human ribosomal RNA gene clustering region (rDNA) has traditionally been hard to analyze due to its highly repetitive nature. However, the recent development of long-read sequencing technology, such as Oxford Nanopore sequencing, has enabled us to approach the large-scale structure of the genome. Using this technology, we found that human cells have a quite regular rDNA structure. Although each human rDNA copy has some variations in its non-coding region, contiguous copies of rDNA are similar, suggesting that homogenization through gene conversion frequently occurs between copies. Analysis of rDNA methylation by Nanopore sequencing further showed that all of the non-coding regions are heavily methylated, whereas about half of the coding regions are clearly unmethylated. The ratio of unmethylated copies, which are speculated to be transcriptionally active, was lower in individuals with a higher rDNA copy number, suggesting that there is a mechanism that keeps the active copy number stable. Lastly, the rDNA in progeroid syndrome patient cells with reduced DNA repair activity had more unstable copies as compared with control normal cells, although the rate was much lower than previously reported using a Fiber FISH method. Collectively, our results alter the view of rDNA stability and transcription regulation in human cells, indicating the presence of mechanisms for both homogenization to ensure sequence quality and maintenance of active copies for cellular functions.
Regulation of suberin biosynthesis and Casparian strip development in the root endodermis by two plant auxins
Authors: Cook Sam David , Kimura Seisuke , Wu Qi , Franke Rochus Benni , Kamiya Takehiro , Kasahara Hiroyuki 
Published: June 2021

AbstractThe biological function of the auxin phenylacetic acid (PAA) is not well characterized in plants. Although some aspects of its biology; transport, signaling and metabolism have recently been described. Previous work on this phytohormone has suggested that PAA behaves in an identical manner to IAA (indole-3-acetic acid) in promoting plant growth, yet plants require greater concentrations of PAA to elicit the same physiological responses. Here we show that normalized PAA treatment results in the differential expression of a unique list of genes, suggesting that plants can respond differently to the two auxins. This is further explored in endodermal barrier regulation where the two auxins invoke striking differences in the deposition patterns of suberin. We further show that auxin acts antagonistically on Casparian strip (CS) formation as it can circumvent the CS transcriptional machinery to repress CS related genes. Additionally, altered suberin biosynthesis reduces endogenous levels of PAA and CS deficiency represses the biosynthesis of IAA and the levels of both auxins. These findings implicate auxin as a regulator of endodermal barrier formation and highlight a novel role for PAA in root development and differentiation.
Characterization of the consensus mucosal microbiome of colorectal cancer
Authors: Zhao Lan , Grimes Susan M. , Greer Stephanie U. , Kubit Matthew , Lee HoJoon , Nadauld Lincoln D. , Ji Hanlee P. 
Published: June 2021

ABSTRACTRecent evidence suggests that dysbiosis, an imbalance of microbiota, is associated with increased risk of colorectal cancer. Diverse microbial organisms are physically associated with the cells found in tumor biopsies. Characterizing this mucosa-associated microbiome through genome sequencing has advantages compared to culture-based profiling. However, there are notable challenges in accurately characterizing the features of tumor microbiomes with methods like transcriptome sequencing. Most sequence reads originate from the host. Moreover, there is a high likelihood of bacterial contaminants being introduced. Another major challenge is the microbiome diversity among different studies. Colorectal tumors demonstrate a significant extent of microbiome variation among individuals from different geographic and ethnic origins. To address these challenges, we identified a consensus microbiome for colorectal cancer through analyzing 924 tumors from eight independent RNA-Seq data sets. A standardized meta-transcriptomic analysis pipeline was established and applied to the complete CRC cohort. Common contaminants were filtered out. Our study involved taxonomic investigation of non-human sequences, linked microbial signatures to phenotypes and the association of microbiome with tumor microenvironment components. Microbiome profiles across different CRC cohorts were compared, and recurrently altered microbial shifts specific to CRC were determined. We identified cancer-specific set of 114 microbial species associated with tumors that were found among all investigated studies. Validating our approach, we found that Fusobacterium nucleatum was one of the most enriched bacterial species in CRC. Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were among the four most abundant phyla for CRC microbiome. Signficant associations between the consensus species and specific immune cell types were noted. Our results are available as a web data resource for other researchers to explore (https://crc-microbiome.stanford.edu).
Distillation of MSA Embeddings to Folded Protein Structures with Graph Transformers
Authors: Costa Allan , Ponnapati Manvitha , Jacobson Joseph M. , Chatterjee Pranam 
Published: June 2021

AbstractDetermining the structure of proteins has been a long-standing goal in biology. Language models have been recently deployed to capture the evolutionary semantics of protein sequences. Enriched with multiple sequence alignments (MSA), these models can encode protein tertiary structure. In this work, we introduce an attention-based graph architecture that exploits MSA Transformer embeddings to directly produce three-dimensional folded structures from protein sequences. We envision that this pipeline will provide a basis for efficient, end-to-end protein structure prediction.
Haemosporidian taxonomic composition, network centrality and partner fidelity between resident and migratory avian hosts
Authors: de Angeli Dutra Daniela , Fecchio Alan , Braga Érika Martins , Poulin Robert 
Published: June 2021

AbstractMigration can modify interaction dynamics between parasites and their hosts with migrant hosts able to disperse parasites and impact local community transmission. Thus, studying the relationships among migratory hosts and their parasites is fundamental to elucidate how migration shapes host-parasite interactions. Avian haemosporidian parasites are some of the most prevalent, diverse, and important wildlife parasites, and are also widely used as models in ecological and evolutionary research. Here, we contrast parasite taxonomic composition, network centrality and partner fidelity among resident and non-resident hosts using avian haemosporidians as study model. In order to evaluate parasite taxonomic composition, we performed permutational multivariate analyses of variance to quantify dissimilarity in haemosporidian lineages infecting different host migratory categories. Additionally, we ran multilevel Bayesian models to assess the role of migration in determining centrality and partner fidelity in host-parasite networks of avian hosts and their respective haemosporidian parasites. We observed similar parasite taxonomic composition and partner fidelity among resident and migratory hosts. Conversely, we demonstrate that migratory hosts play a more central role in host-parasite networks than residents. However, when evaluating partially and fully migratory hosts separately, we observed that only partially migratory species presented higher network centrality when compared to resident birds. Therefore, migration does not lead to differences in both parasite taxonomic composition and partner fidelity. However, migratory behavior is positively associated with network centrality, indicating migratory hosts play more important roles in shaping host-parasite interactions and influence local transmission.
Chronic opioid treatment arrests neurodevelopment and alters synaptic activity in human midbrain organoids
Authors: Kim Hye Sung , Xiao Yang , Chen Xuejing , He Siyu , Im Jongwon , Willner Moshe J. , Finlayson Michael O. , Xu Cong , Zhu Huixiang , Choi Se Joon , Mosharov Eugene V. , Kim Hae-Won , Xu Bin , Leong Kam W. 
Published: June 2021

SummaryThe impact of long-term opioid exposure on the embryonic brain is crucial to healthcare due to the surging number of pregnant mothers with an opioid dependency. Current studies on the neuronal effects are limited due to human brain inaccessibility and cross-species differences among animal models. Here, we report a model to assess cell-type specific responses to acute and chronic fentanyl treatment, as well as fentanyl withdrawal, using human induced pluripotent stem cell (hiPSC)-derived midbrain organoids. Single cell mRNA sequencing (25,510 single cells in total) results suggest that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters the pathways associated with synaptic activities and neuron projection. Acute fentanyl treatment, however, increases dopamine release but does not induce significant changes in gene expressions of cell lineage development. To date, our study is the first unbiased examination of midbrain transcriptomics with synthetic opioid treatment at the single cell level.
A homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium
Authors: Van Winkle Jacob A. , Peterson Stefan T. , Kennedy Elizabeth A. , Wheadon Michael J. , Ingle Harshad , Desai Chandni , Rodgers Rachel , Constant David A. , Wright Austin P. , Li Lena , Artyomov Maxim , Lee Sanghyun , Baldridge Megan T. , Nice Timothy J. 
Published: June 2021

AbstractInterferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor (Ifnlr1), and is associated with IFN-λ production by leukocytes. Strikingly, imaging of these homeostatic ISGs reveals localization to pockets of the epithelium and concentration in mature IECs. Correspondingly, a minority of mature IECs express these ISGs in public single-cell RNA sequencing datasets from mice and humans. Furthermore, we assessed the ability of orally-administered bacterial components to restore localized ISGs in mice lacking bacterial microbiota. Lastly, we find that IECs lacking Ifnlr1 are hyper-susceptible to initiation of murine rotavirus infection. These observations indicate that bacterial microbiota stimulate ISGs in localized regions of the intestinal epithelium at homeostasis, thereby preemptively activating antiviral defenses in vulnerable IECs to improve host defense against enteric viruses.
Heavy-tailed distributions in a stochastic gene autoregulation model
Authors: Bokes Pavol 
Published: June 2021

AbstractSynthesis of gene products in bursts of multiple molecular copies is an important source of gene expression variability. This paper studies large deviations in a Markovian drift–jump process that combines exponentially distributed bursts with deterministic degradation. Large deviations occur as a cumulative effect of many bursts (as in diffusion) or, if the model includes negative feedback in burst size, in a single big jump. The latter possibility requires a modification in the WKB solution in the tail region. The main result of the paper is the construction, via a modified WKB scheme, of matched asymptotic approximations to the stationary distribution of the drift–jump process. The stationary distribution possesses a heavier tail than predicted by a routine application of the scheme.MSC 202092C40; 60J76, 45D05, 41A60
Zebrafish Danio rerio trunk muscle structure and growth from a spatial transcriptomics perspective
Authors: Liu Guanting , Ito Takumi , Kijima Yusuke , Yoshitake Kazutoshi , Asakawa Shuichi , Watabe Shugo , Kinoshita Shigeharu 
Published: June 2021

AbstractCompared to mammals, some fish exhibit indeterminate growth characteristics, meaning they can continue growing throughout their lives. Zebrafish trunk skeletal muscle can in general be classified into slow, intermediate, and fast based on morphological and physiological characteristics. After hatching, hyperplasia can be observed in the muscles of juvenile zebrafish, and with growth, hyperplasia in the fast muscles gradually decreases until it stagnates, after which fast muscle development relies on hypertrophy. In slow muscle, hyperplasia continues throughout life. Teleost muscle structure and growth has been described mainly by morphological and physiological features based on the expression of a limited number of proteins, transcripts, and metabolites. The details of mechanism remain unclear. Visium Spatial Gene Expression solution was used in this study. On the adult slide, 10 clusters were obtained based on whole gene expression similarities. The spatial expression of myosin heave chains, myosin light chains and myosin-binding proteins was investigated. GO enrichment analysis was also performed on different muscle regions of aged zebrafish. Dorsal and ventral slow muscles share the same processes such as myofibril assembly and muscle tissue development. On the larvae slide, 3 clusters were obtained, GO enrichment analysis suggest active muscle formation in zebrafish larvae.
Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age
Authors: Dimitrova Ralica , Pietsch Maximilian , Ciarrusta Judit , Fitzgibbon Sean P. , Williams Logan Z. J. , Christiaens Daan , Cordero-Grande Lucilio , Batalle Dafnis , Makropoulos Antonios , Schuh Andreas , Price Anthony N. , Hutter Jana , Teixeira Rui PAG , Hughes Emer , Chew Andrew , Falconer Shona , Carney Olivia , Egloff Alexia , Tournier J-Donald , McAlonan Grainne , Rutherford Mary A. , Counsell Serena J. , Robinson Emma C. , Hajnal Joseph V. , Rueckert Daniel , Edwards A. David , O’Muircheartaigh Jonathan 
Published: June 2021

AbstractIntroductionThe dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors.MethodsWe sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months.ResultsIn the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months.ConclusionWe showed that preterm birth alters cortical micro and macrostructural maturation near the time of fullterm birth. Deviations from normative development were highly variable between individual preterm infants.
The vagus nerve is critical for regulation of hypothalamic-pituitary-adrenal axis responses to acute stress
Authors: Keller Bailey N. , Snyder Angela E. , Coker Caitlin R. , Aguilar Elizabeth A. , O’Brien Mary K. , Bingaman Sarah S. , Arnold Amy C. , Hajnal Andras , Silberman Yuval 
Published: June 2021

AbstractThe hypothalamic pituitary adrenal (HPA) axis is a critical regulator of physiologic and psychological responses to acute and chronic stressors. HPA axis function is control by numerous feedback inhibitory mechanisms, disruptions of which can lead to various psychiatric conditions, such as depression, posttraumatic stress disorder, and schizophrenia. Vagus nerve stimulation has been shown to be efficacious in the treatment of in these various mental health issues potentially via modulation of HPA axis function, but the mechanisms by which the vagus nerve may regulate HPA function has not been fully elucidated. In the present studies, we sought to test the hypothesis that the vagus nerve is a critical regulator of HPA function. Neuroendocrine function and neurocircuit changes in corticotropin releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) were examined following acute stress after subdiaphragmatic left vagotomy (VX) in adult male Sprague-Dawley rats. We found that VX mimics HPA activation seen in sham surgery animals exposed to acute restraint stress, particularly increased plasma corticosterone levels, elevated PVN CRF mRNA, and increased action potential firing of putative CRF neurons in PVN brain slices. Furthermore, VX animals exposed to acute restraint stress showed increased elevations of plasma corticosterone and PVN CRF mRNA which may be due to lack of compensatory PVN GABAergic signaling in response to acute stress. Both Sham/Stress and VX/no stress conditions increased action potential firing in putative PVN CRF neurons, but this effect was not seen in the VX/stress condition, suggesting that not all forms of stress compensation are lost following VX. Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of local PVN neurocircuit activity.
M1-linked ubiquitination facilitates NF-κB activation during sterile inflammation
Authors: Aalto Anna , Martínez-Chacón Gabriela , Tsyganova Nadezhda , Kreutzer Joose , Kallio Pasi , Broemer Meike , Meinander Annika 
Published: June 2021

AbstractMethionine 1 (M1)-linked ubiquitination plays a key role in the regulation of inflammatory nuclear factor-κB (NF-κB) signalling and is important for clearance of pathogen infection in Drosophila melanogaster. M1-linked ubiquitin (M1-Ub) chains are assembled by the linear ubiquitin E3 ligase (LUBEL) in flies. Here, we have studied the role of LUBEL in sterile inflammation induced by different types of cellular stresses. We have found that LUBEL catalyses formation of M1-Ub chains in response to hypoxic, oxidative and mechanical stress conditions. LUBEL is shown to be important for flies to survive low oxygen conditions and paraquat-induced oxidative stress. This protective action seems to be driven by stress-induced activation of the NF-κB transcription factor Relish via the Immune deficiency (Imd) pathway. In addition to LUBEL, the intracellular mediators of Relish activation, including the Drosophila inhibitor of apoptosis (IAP) Diap2, the IκB kinase γ (IKKγ) Kenny and the initiator caspase Death-related ced-3/Nedd2-like protein (Dredd), but not the membrane receptor peptidoglycan recognition protein (PGRP)-LC, are shown to be required for sterile inflammatory response and survival. Finally, we showed that the stress-induced upregulation of M1-Ub chains in response to hypoxia, oxidative and mechanical stress is also induced in mammalian cells. Taken together, our results suggest that M1-Ub chains are important for NF-κB signalling in inflammation induced by stress conditions often observed in chronic inflammatory diseases and cancer.