bluuebunny/crossref_metadata_2025_split huggingface dataset:
A general model to explain repeated turnovers of sex determination in the Salicaceae
Authors: Yang Wenlu , Zhang Zhiyang , Wang Deyan , Li Yiling , Tong Shaofei , Li Mengmeng , Zhang Xu , Zhang Lei , Ren Liwen , Ma Xinzhi , Zhou Ran , Sanderson Brian J. , Keefover-Ring Ken , Yin Tongming , Smart Lawrence B. , Liu Jianquan , DiFazio Stephen P. , Olson Matthew , Ma Tao 
Published: April 2020

AbstractDioecy, the presence of separate sexes on distinct individuals, has evolved repeatedly in multiple plant lineages. However, the specific mechanisms through which sex systems evolve and their commonalities among plant species remain poorly understood. With both XY and ZW sex systems, the family Salicaceae provides a system to uncover the evolutionary forces driving sex chromosome turnovers. In this study, we performed a genome-wide association study to characterize sex determination in twoPopulusspecies,P. euphraticaandP. alba. Our results reveal an XY system of sex determination on chromosome 14 ofP. euphratica, and a ZW system on chromosome 19 ofP. alba. We further assembled the corresponding sex determination regions, and found that their sex chromosome turnovers may be driven by the repeated translocations of aHelitron-like transposon. During the translocation, this factor may have captured partial or intact sequences that are orthologous to a type-A cytokinin response regulator gene. Based on results from this and other recently published studies, we hypothesize that this gene may act as a master regulator of sex determination for the entire family. We propose a general model to explain how the XY and ZW sex systems in this family can be determined by the sameRRgene. Our study provides new insights into the diversification of incipient sex chromosome in flowering plants by showing how transposition and rearrangement of a single gene can control sex in both XY and ZW systems.
Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM
Authors: Hopp Christine S. , Diouf Ababacar , Miura Kazutoyo , Boswell Kristin , Sekar Padmapriya , Skinner Jeff , Tipton Christopher M. , Chambers Michael , Andrews Sarah , Tan Joshua , Li Shanping , Doumbo Safiatou , Kayentao Kassoum , Ongoiba Aissata , Traore Boubacar , Portugal Silvia , Long Carole , Koup Richard A. , Long Eric , McDermott Adrian B. , Crompton Peter D. 
Published: April 2020

AbstractIgG antibodies are known to play a central role in naturally acquired immunity to blood-stage malaria in humans, but little is known about the IgM response to blood-stage malaria, the mechanisms by which IgM may protect, or the underlying biology ofPlasmodium falciparum(Pf)-specific IgM B cells. In a Mali cohort spanning infants to adults we conducted a longitudinal analysis of B cells specific for thePfblood-stage antigens AMA1 and MSP1, as well as the comparator antigen influenza hemagglutinin (HA). At the uninfected baseline, before the malaria season,Pf-specific memory B cells (MBCs) in children are disproportionally IgM+and only gradually shift to IgG+with age, in contrast to HA-specific MBCs that are predominantly IgG+from infancy to adulthood. In response to acute febrile malaria,Pf-specific IgM B cells increase in frequency and upregulate activation and co-stimulatory markers. B cell receptor (BCR) analysis showed thatPf-specific IgM B cells are somatically hypermutated at levels comparable to HA-specific IgG B cells. Finally, IgM antibodies from the plasma of malaria-exposed individuals were comparable to IgG in inhibitingPfblood-stage growthin vitro, and significantly better at enhancing phagocytosis ofPfmerozoites, suggesting that IgM may protect through both direct neutralization and opsonization. Thus, somatically hypermutatedPf-specific IgM MBCs dominate in early life, are activated and expand during acute malaria and are associated with plasma IgM that inhibits parasite growthin vitro.
ASpediaFI: Functional interaction analysis of alternative splicing events
Authors: Yu Doyeong , Lee Kyubin , Hyung Daejin , Cho Soo Young , Park Charny 
Published: April 2020

ABSTRACTAlternative splicing (AS) regulates biological process governing phenotype or disease. However, it is challenging to systemically analyze global regulation of AS events, their gene interactions, and functions. Here, we introduce a novel application, ASpediaFI for identifying AS events and co-regulated gene interactions implicated in pathways. Our method establishes an interaction network including AS events, performs random walk with restart, and finally identifies a functional subnetwork containing the AS event. We validated the capability of ASpediaFI to interpret biological relevance based on three case studies. Using simulation data, we achieved higher accuracy than with other methods and detected pathway-associated AS events.
Alternative MyD88 -Cyclin D1 signaling in breast cancer cells regulates TLR3 mediated cell proliferation
Authors: Singh Aradhana , Devkar Ranjitsinh , Basu Anupam 
Published: April 2020

AbstractTLR3 mediated apoptotic changes in cancer cells are well documented and hence several synthetic ligands of TLR3 are being used for adjuvant therapy. But there are reports showing contradictory effect of TLR3 signaling which includes our previous report that had shown cell proliferation following surface localization of TLR 3. However, the underlying mechanism of cell surface localization of TLR3 and subsequent cell proliferation lacks clarity. This study addresses TLR3 ligand mediated signaling cascade that regulates a proliferative effect in breast cancer cells (MDA MB 231 and T47D) challenged with TLR3 ligand in the presence of MyD88 inhibitor. Evidences were obtained using immunoblotting, co-immunoprecipitation, confocal microscopy, Immunocytochemistry, ELISA, and flowcytometry. Results had revealed that TLR3 ligand treatment significantly enhanced breast cancer cell proliferation marked by an upregulated expression of cyclinD1 but the same were suppressed by addition of MyD88 inhibitor. Also, expression of IRAK1-TRAF6-TAK1 were altered in the given TLR3-signaling pathway. Inhibition of MyD88 disrupted the downstream adaptor complex and mediated signaling through TLR3-MyD88-NF-κB (p65)-IL6-Cyclin D1 pathway. TLR3 mediated alternative signaling of the TLR3-MyD88-IRAK1-TRAF6-TAK1-TAB1-NF-κB axis leads to upregulation of IL6 and cyclinD1. This response is hypothesized to be via the MyD88 gateway that culminates in proliferation of breast cancer cells. Overall, this study provides first comprehensive evidence on involvement of canonical signaling of TLR3 using MyD88 - Cyclin D1 mediated breast cancer cell proliferation. The findings elucidated herein will provide valuable insights into understand the TLR3 mediated adjuvant therapy in cancer.
Genomic Architecture of Cells in Tissues (GeACT): Study of Human Mid-gestation Fetus
Authors: Tian Feng , Zhou Fan , Li Xiang , Ma Wenping , Wu Honggui , Yang Ming , Chapman Alec R. , Lee David F. , Tan Longzhi , Xing Dong , Yin Guangjun , Semayel Ayjan , Wang Jing , Wang Jia , Sun Wenjie , He Runsheng , Zhang Siwei , Cao Zhijie , Wei Lin , Lu Shen , Yang Dechang , Mao Yunuo , Gao Yuan , Chen Kexuan , Zhang Yu , Liu Xixi , Yong Jun , Yan Liying , Huang Yanyi , Qiao Jie , Tang Fuchou , Gao Ge , Xie X. Sunney 
Published: April 2020

SummaryBy circumventing cellular heterogeneity, single cell omics have now been widely utilized for cell typing in human tissues, culminating with the undertaking of human cell atlas aimed at characterizing all human cell types. However, more important are the probing of gene regulatory networks, underlying chromatin architecture and critical transcription factors for each cell type. Here we report the Genomic Architecture of Cells in Tissues (GeACT), a comprehensive genomic data base that collectively address the above needs with the goal of understanding the functional genome in action. GeACT was made possible by our novel single-cell RNA-seq (MALBAC-DT) and ATAC-seq (METATAC) methods of high detectability and precision. We exemplified GeACT by first studying representative organs in human mid-gestation fetus. In particular, correlated gene modules (CGMs) are observed and found to be cell-type-dependent. We linked gene expression profiles to the underlying chromatin states, and found the key transcription factors for representative CGMs.HighlightsGenomic Architecture of Cells in Tissues (GeACT) data for human mid-gestation fetusDetermining correlated gene modules (CGMs) in different cell types by MALBAC-DTMeasuring chromatin open regions in single cells with high detectability by METATACIntegrating transcriptomics and chromatin accessibility to reveal key TFs for a CGM
Scalable hierarchical clustering by composition rank vector encoding and tree structure
Authors: Lai Xiao , Tian Pu 
Published: April 2020

AbstractSupervised machine learning, especially deep learning based on a wide variety of neural network architectures, have contributed tremendously to fields such as marketing, computer vision and natural language processing. However, development of un-supervised machine learning algorithms has been a bottleneck of artificial intelligence. Clustering is a fundamental unsupervised task in many different subjects. Unfortunately, no present algorithm is satisfactory for clustering of high dimensional data with strong nonlinear correlations. In this work, we propose a simple and highly efficient hierarchical clustering algorithm based on encoding by composition rank vectors and tree structure, and demonstrate its utility with clustering of protein structural domains. No record comparison, which is an expensive and essential common step to all present clustering algorithms, is involved. Consequently, it achieves linear time and space computational complexity hierarchical clustering, thus applicable to arbitrarily large datasets. The key factor in this algorithm is definition of composition, which is dependent upon physical nature of target data and therefore need to be constructed case by case. Nonetheless, the algorithm is general and applicable to any high dimensional data with strong nonlinear correlations. We hope this algorithm to inspire a rich research field of encoding based clustering well beyond composition rank vector trees.
The rates of introgression and barriers to genetic exchange between hybridizing species: sex chromosomes vs. autosomes
Authors: Fraïsse Christelle , Sachdeva Himani 
Published: April 2020

ABSTRACTInterspecific crossing experiments have shown that sex chromosomes play a major role in reproductive isolation between many pairs of species. However, their ability to act as reproductive barriers, which hamper interspecific genetic exchange, has rarely been evaluated quantitatively compared to Autosomes. This genome-wide limitation of gene flow is essential for understanding the complete separation of species, and thus speciation. Here, we develop a mainland-island model of secondary contact between hybridizing species of an XY (or ZW) sexual system. We obtain theoretical predictions for the frequency of introgressed alleles, and the strength of the barrier to neutral gene flow for the two types of chromosomes carrying multiple interspecific barrier loci. Theoretical predictions are obtained for scenarios where introgressed alleles are rare. We show that the same analytical expressions apply for sex chromosomes and autosomes, but with different sex-averaged effective parameters. The specific features of sex chromosomes (hemizygosity and absence of recombination in the heterogametic sex) lead to reduced levels of introgression on the X (or Z) compared to autosomes. This effect can be enhanced by certain types of sex-biased forces, but it remains overall small (except when alleles causing incompatibilities are recessive). We discuss these predictions in the light of empirical data comprising model-based tests of introgression and cline surveys in various biological systems.
Clustering and reverse transcription of HIV-1 genomes in nuclear niches of macrophages
Authors: Rensen Elena , Mueller Florian , Scoca Viviana , Parmar Jyotsana J. , Souque Philippe , Zimmer Christophe , Di Nunzio Francesca 
Published: April 2020

SummaryIn order to replicate, the Human Immunodeficiency Virus (HIV-1) reverse transcribes its RNA genome into DNA, which subsequently integrates into host cell chromosomes. These two key events of the viral life cycle are commonly viewed as separate not only in time but also in cellular space, since reverse transcription (RT) is thought to be completed in the cytoplasm before nuclear import and integration. However, the spatiotemporal organization of the early replication cycle in macrophages, natural non-dividing target cells that constitute reservoirs of HIV-1 and an obstacle to curing AIDS, remains unclear. Here, we demonstrate that infected macrophages display large nuclear foci of viral DNA and viral RNA, in which multiple genomes cluster together. These clusters form in the absence of chromosomal integration, sequester the paraspeckle protein CPSF6 and localize to nuclear speckles. Strikingly, we show that viral RNA clusters consist mostly of genomic, incoming RNA, both in cells where RT is pharmacologically suppressed and in untreated cells. We demonstrate that, after temporary inhibition, RT can resume in the nucleus and lead to vDNA accumulation in these clusters. We further show that nuclear RT can result in transcription competent viral DNA. These findings change our understanding of the early HIV-1 replication cycle, and may have implications for understanding HIV-1 persistence.
Precise triggering and chemical control of single-virus fusion within endosomes
Authors: Haldar Sourav , Okamoto Kenta , Kasson Peter M. 
Published: April 2020

AbstractMany enveloped viruses infect cells within endocytic compartments. The drop in pH that accompanies endosomal maturation, often in conjunction with proteolytic factors, serves as a trigger for viral fusion proteins to insert into the endosomal membrane and drive fusion. The dynamics of this process has been studied by tracking viruses within living cells, which limits the precision with which fusion can be synchronized and controlled, and by reconstituting viral fusion to synthetic membranes, which introduces non-physiological membrane curvature and composition. To overcome these limitations, we have engineered the chemically controllable triggering of single-virus fusion within endosomes. We isolate influenza virus:endosome conjugates from cells prior to fusion, immobilize them in a microfluidic flow cell, and then rapidly and controllably trigger fusion. This platform demonstrates lipid-mixing kinetics that are grossly similar to influenza fusion with model membranes but display some subtle differences. Because it preserves endosomal membrane asymmetry and protein composition, it also provides a means to test how perturbations to endosomal trafficking and cellular restriction factors affect viral membrane fusion.
Modern Hopfield Networks and Attention for Immune Repertoire Classification
Authors: Widrich Michael , Schäfl Bernhard , Pavlović Milena , Ramsauer Hubert , Gruber Lukas , Holzleitner Markus , Brandstetter Johannes , Sandve Geir Kjetil , Greiff Victor , Hochreiter Sepp , Klambauer Günter 
Published: April 2020

AbstractA central mechanism in machine learning is to identify, store, and recognize patterns. How to learn, access, and retrieve such patterns is crucial in Hopfield networks and the more recent transformer architectures. We show that the attention mechanism of transformer architectures is actually the update rule of modern Hop-field networks that can store exponentially many patterns. We exploit this high storage capacity of modern Hopfield networks to solve a challenging multiple instance learning (MIL) problem in computational biology: immune repertoire classification. Accurate and interpretable machine learning methods solving this problem could pave the way towards new vaccines and therapies, which is currently a very relevant research topic intensified by the COVID-19 crisis. Immune repertoire classification based on the vast number of immunosequences of an individual is a MIL problem with an unprecedentedly massive number of instances, two orders of magnitude larger than currently considered problems, and with an extremely low witness rate. In this work, we present our novel method DeepRC that integrates transformer-like attention, or equivalently modern Hopfield networks, into deep learning architectures for massive MIL such as immune repertoire classification. We demonstrate that DeepRC outperforms all other methods with respect to predictive performance on large-scale experiments, including simulated and real-world virus infection data, and enables the extraction of sequence motifs that are connected to a given disease class. Source code and datasets:https://github.com/ml-jku/DeepRC
Crosstalk between microRNA expression and DNA methylation drive the hormone-dependent phenotype of breast cancer
Authors: Aure Miriam Ragle , Fleischer Thomas , Bjørklund Sunniva , Ankill Jørgen , Castro-Mondragon Jaime A. ,   OSBREAC, Børresen-Dale Anne-Lise , Sahlberg Kristine K. , Mathelier Anthony , Tekpli Xavier , Kristensen Vessela N. 
Published: April 2020

AbstractBackgroundAbnormal DNA methylation is observed as an early event in breast carcinogenesis. However, how such alterations arise is still poorly understood. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and have been shown to play key roles in various biological processes. Here, we integrate miRNA expression and DNA methylation at CpGs to study how miRNAs may affect the breast cancer methylome and how DNA methylation may regulate miRNA expression.ResultsmiRNA expression and DNA methylation data from two breast cancer cohorts were subjected to genome-wide correlation analysis. Clustering of the miRNA expression-DNA methylation association pairs significant in both cohorts identified distinct clusters of miRNAs and CpGs. These clusters recapitulated important biological processes associated with breast cancer pathogenesis. Notably, two major clusters were related to immune or fibroblast infiltration, hence identifying miRNAs associated with cells of the tumor microenvironment, while another large cluster was related to estrogen receptor (ER) signaling. Studying the chromatin landscape surrounding the CpGs associated with the estrogen-signaling cluster, we found that miRNAs from this cluster are likely to be regulated through DNA methylation of enhancers bound by FOXA1, GATA2 and ER-alpha. Further, at the hub of the estrogen-cluster, we identified hsa-miR-29c-5p as negatively correlated with the mRNA and protein expression of the DNA methyltransferase DNMT3A, a key enzyme regulating DNA methylation. We found deregulation of hsa-miR-29c-5p already in pre-invasive breast lesions and postulate that hsa-miR-29c-5p may trigger early event abnormal DNA methylation in ER positive breast cancer.ConclusionsWe describe how miRNA expression and DNA methylation interact and associate with distinct breast cancer phenotypes.
Co-activation of NF-κB and MYC renders cancer cells addicted to IL6 for survival and phenotypic stability
Authors: Barbosa RR , Xu AQ , D’Andrea D , Copley F , Patel H , Chakravarty P , Clear A , Calaminici M , Janz M , Zhang B , Schmidt-Supprian M , Wang J , Gribben JG , Tooze R , Fitzgibbon J , Franzoso G , Rajewsky K , Calado DP 
Published: April 2020

SummaryNF-κB and MYC are found co-deregulated in human B and plasma-cell cancers. In physiology, NF-κB is necessary for terminal B-to-plasma cell differentiation, whereas MYC repression is required. It is thus unclear if NF-κB/MYC co-deregulation is developmentally compatible in carcinogenesis and/or impacts cancer cell differentiation state, possibly uncovering unique sensitivities. Using a mouse system to trace cell lineage and oncogene activation we found that NF-κB/MYC co-deregulation originated cancers with a plasmablast-like phenotype, alike human plasmablastic-lymphoma and was linked to t(8;14)[MYC-IGH] multiple myeloma. Notably, in contrast to NF-κB or MYC activation alone, co-deregulation rendered cells addicted to IL6 for survival and phenotypic stability. We propose that conflicting oncogene-driven differentiation pressures can be accommodated at a cost in poorly-differentiated cancers.SignificanceOur studies improve the understanding of cancer pathogenesis by demonstrating that co-deregulation of NF-κB and MYC synergize in forming a cancer with a poorly-differentiated state. The cancers in the mouse system share features with human Plasmablastic lymphoma that has a dismal prognosis and no standard of care, and with t(8;14)[MYC-IGH] Multiple myeloma, which is in overall resistant to standard therapy. Notably, we found that NF-κB and MYC co-deregulation uniquely render cells sensitive to IL6 deprivation, providing a road-map for patient selection. Because of the similarity of the cancers arising in the compound mutant mouse model with that of human Plasmablastic lymphoma and t(8;14)[MYC-IGH] Multiple myeloma, this model could serve in preclinical testing to investigate novel therapies for these hard-to-treat diseases.HighlightsNF-κB and MYC co-activation originates (pre)plasmablast-like cancerNF-κB/MYC+renders cancer cells addicted to IL6 for survival and phenotypic stabilityNF-κB/MYC+cancers are alike a fraction of human plasmablastic lymphomat(8;14)[MYC-IGH] multiple myeloma is linked to a NF-κB/MYC co-activation signature
Visualization of seasonal phosphorus re-translocation, and expression profile of phosphate transporters in a shortened annual cycle system of the deciduous poplar tree
Authors: Kurita Yuko , Kanno Satomi , Sugita Ryohei , Hirose Atsushi , Ohnishi Miwa , Tezuka Ayumi , Deguchi Ayumi , Ishizaki Kimitsune , Fukaki Hidehiro , Baba Kei’ichi , Nagano Atsushi J. , Tanoi Keitaro , Nakanishi Tomoko M. , Mimura Tetsuro 
Published: April 2020

AbstractPhosphorus (P) is an essential macronutrient for plant growth. In deciduous trees, P is remobilized from senescing leaves and stored in perennial tissues during winter for further growth. Annual internal recycling and accumulation of P is considered an important strategy to support vigorous growth of trees. However, the pathways of seasonal re-translocation of P and the molecular mechanisms of this transport have not been clarified. Here we show the seasonal P re-translocation route visualized using the real-time radioisotope imaging and the macro- and micro-autoradiography. We analyzed the seasonal re-translocation P in poplar (Populus alba. L) cultivated under “a shortened annual cycle system”, which mimicked seasonal phenology in a laboratory. From growing to senescing season, sink tissues of32P and/or33P shifted from young leaves and the apex to the lower stem and roots. The radioisotope P re-translocated from a leaf was stored in phloem and xylem parenchyma cells and redistributed to new shoots after dormancy. Seasonal expression profile of phosphate transporters (PHT1,PHT5andPHO1family) was obtained in the same system. Our results reveal the seasonal P re-translocation routes at the organ and tissue levels and provide a foothold for elucidating its molecular mechanisms.