bluuebunny/crossref_metadata_2025_split huggingface dataset:
Style Transfer Using Generative Adversarial Networks for Multi-Site MRI Harmonization
Authors: Liu Mengting , Maiti Piyush , Thomopoulos Sophia , Zhu Alyssa , Chai Yaqiong , Kim Hosung , Jahanshad Neda 
Published: March 2021

AbstractLarge data initiatives and high-powered brain imaging analyses require the pooling of MR images acquired across multiple scanners, often using different protocols. Prospective cross-site harmonization often involves the use of a phantom or traveling subjects. However, as more datasets are becoming publicly available, there is a growing need for retrospective harmonization, pooling data from sites not originally coordinated together. Several retrospective harmonization techniques have shown promise in removing cross-site image variation. However, most unsupervised methods cannot distinguish between image-acquisition based variability and cross-site population variability, so they require that datasets contain subjects or patient groups with similar clinical or demographic information. To overcome this limitation, we consider cross-site MRI image harmonization as a style transfer problem rather than a domain transfer problem. Using a fully unsupervised deep-learning framework based on a generative adversarial network (GAN), we show that MR images can be harmonized by inserting the style information encoded from a reference image directly, without knowing their site/scanner labelsa priori. We trained our model using data from five large-scale multi-site datasets with varied demographics. Results demonstrated that our styleencoding model can harmonize MR images, and match intensity profiles, successfully, without relying on traveling subjects. This model also avoids the need to control for clinical, diagnostic, or demographic information. Moreover, we further demonstrated that if we included diverse enough images into the training set, our method successfully harmonized MR images collected from unseen scanners and protocols, suggesting a promising novel tool for ongoing collaborative studies.
Efficiency of the synthetic self-splicing RiboJ ribozyme is robust tocis- andtrans-changes in genetic background
Authors: Vlková Markéta , Morampalli Bhargava Reddy , Silander Olin K. 
Published: March 2021

AbstractThe expanding knowledge of the variety of synthetic genetic elements has enabled the construction of new and more efficient genetic circuits and yielded novel insights into molecular mechanisms. However, context dependence, in which interactions between proximal (cis) or distal (trans) elements affect the behaviour of these elements, can reduce their general applicability or predictability. Genetic insulators, which mitigate unintended context-dependentcis-interactions, have been used to address this issue. One of the most commonly used genetic insulators is a self-splicing ribozyme called RiboJ, which can be used to decouple upstream 5’ UTR in mRNA from downstream sequences (e.g., open reading frames). Despite its general use as an insulator, there has been no systematic study quantifying the efficiency of RiboJ splicing or whether this autocatalytic activity is robust totrans- andcis-genetic context. Here, we determine the robustness of RiboJ splicing in the genetic context of six widely divergentE. colistrains. We also check for possiblecis-effects by assessing two SNP versions close to the catalytic site of RiboJ. We show that mRNA molecules containing RiboJ are rapidly spliced even during rapid exponential growth and high levels of gene expression, with a mean efficiency of 98%. We also show that neither thecis- nortrans-genetic context has a significant impact on RiboJ activity, suggesting this element is robust to bothcis- andtrans-genetic changes.
High throughput genome-wide single cell protein:DNA binding site mapping by targeted insertion of promoters (TIP-seq)
Authors: Bartlett Daniel A. , Dileep Vishnu , Henikoff Steve , Gilbert David M. 
Published: March 2021

ABSTRACTAssessing cell to cell, and importantly, chromosome to chromosome, heterogeneity in cellular phenotypes is a central goal of modern cell biology. However, chromatin profiling in single cells has been extremely challenging, and single chromosome profiling has not been achieved. In cases where single cell methods have shown promise, success has been mainly limited to histone proteins and/or require highly specialized equipment or cell type specific protocols and are relatively low throughput. Here, we have combined the advantages of tagmentation, linear amplification and combinatorial indexing to produce a high throughput single cell DNA binding site mapping method that does not require specialized equipment and is capable of multiplexing several samples/ target proteins in one experiment. Targeted Insertion of Promoters (TIP-seq) uses Tn5 fused to protein A (as with CUT&Tag) to insert a T7 RNA polymerase promoter into sites adjacent to an antibody bound to a chromatin protein of interest, followed by linear amplification of flanking DNA with T7 polymerase, cDNA preparation and PCR indexing. Tip-seq provides ∼10-fold higher unique reads and thus higher coverage per single cell compared to state-of-the-art methods. We apply TIP-seq to map histone modifications, RNA PolII and CTCF binding sites in single human and mouse cells. TIP-seq will also be adaptable for other platforms, such as 10X genomics and ICELL8. In summary, TIP-seq provides a high-throughput, low-cost method for single cell protein mapping, that yields substantially higher coverage per cell and signal to noise than existing methods.
Decreased synthesis and variable gene transcripts of oxytocin in a domesticated avian species
Authors: Tobari Yasuko , Theofanopoulou Constantina , Mori Chihiro , Sato Yoshimi , Marutani Momoka , Fujioka Sayaka , Konno Norifumi , Suzuki Kenta , Furutani Akari , Hakataya Shiomi , Yao Cheng-Te , Yang En-Yun , Tsai Chia-Ren , Tang Pin-Chi , Chen Chih-Feng , Boeckx Cedric , Jarvis Erich D. , Okanoya Kazuo 
Published: March 2021

AbstractThe Bengalese finch was domesticated more than 250 years ago from the wild white-rumped munia. Similar to other domesticated species, Bengalese finches show a reduced fear response and have lower corticosterone levels, compared to white-rumped munias. Bengalese finches and munias also have different song types. Since oxytocin (OT) has been found to be involved in stress coping and auditory processing, we tested whether theOTsequence and brain expression pattern and content differ in wild munias and domesticated Bengalese finches. We identified intra-strain variability in the untranslated regions of theOTsequence in Bengalese finches in comparison to the muniaOT. Several of these changes fall in specific transcription factor binding sites, which show either a conserved or a relaxed evolutionary trend in the avian lineage, and in vertebrates in general. Althoughin situhybridization in several hypothalamic nuclei did not reveal significant differences in the number of cells expressingOTbetween the two strains, real-time quantitative PCR showed significantly lowerOTmRNA expression in the diencephalon of the Bengalese finches relative to munias. Our study thus points to a decreasedOTsynthesis in the domestic strain compared with the wild strain in birds. This is an opposite pattern from that found in some domesticated mammals, suggesting that different processes ofOTfunction might have occurred in mammals and birds under domestication.
Micro-region transcriptomics of fixed human tissue using Pick-Seq
Authors: Maliga Zoltan , Nirmal Ajit J. , Ericson Nolan G. , Boswell Sarah A. , U’Ren Lance , Podyminogin Rebecca , Chow Jennifer , Chen Yu-An , Chen Alyce A. , Weinstock David M. , Lian Christine G. , Murphy George F. , Kaldjian Eric P. , Santagata Sandro , Sorger Peter K. 
Published: March 2021

ABSTRACTSpatial transcriptomics and multiplexed imaging are complementary methods for studying tissue biology and disease. Recently developed spatial transcriptomic methods use fresh-frozen specimens but most diagnostic specimens, clinical trials, and tissue archives rely on formaldehyde-fixed tissue. Here we describe the Pick-Seq method for deep spatial transcriptional profiling of fixed tissue. Pick-Seq is a form of micro-region sequencing in which small regions of tissue, containing 5-20 cells, are mechanically isolated on a microscope and then sequenced. We demonstrate the use of Pick-Seq with several different fixed and frozen human specimens. Application of Pick-Seq to a human melanoma with complex histology reveals significant differences in transcriptional programs associated with tumor invasion, proliferation, and immuno-editing. Parallel imaging confirms changes in immuno-phenotypes and cancer cell states. This work demonstrates the ability of Pick-Seq to generate deep spatial transcriptomic data from fixed and archival tissue with multiplexed imaging in parallel.
Targetingde novolipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer
Authors: Bartolacci Caterina , Andreani Cristina , Vias Do Vale Gonçalo , Berto Stefano , Melegari Margherita , Crouch Anna C. , Baluya Dodge L. , Kemble George , Hodges Kurt , Starrett Jacqueline , Politi Katerina , Starnes Sandra L. , Lorenzini Daniele , Raso Maria Gabriela , Soto Luisa Solis , Behrens Carmen , Kadara Humam , Gao Boning , Gerber David , Wistuba Ignacio I. , Minna John D. , McDonald Jeffrey , Scaglioni Pier Paolo 
Published: March 2021

AbstractMutantKRAS(KM) is the most common oncogene in lung cancer (LC). KM regulates several metabolic networks, but their role in tumorigenesis is still not sufficiently characterized to be exploited in cancer therapy. To identify metabolic networks specifically deregulated in KMLC, we characterized the lipidome of genetically engineered LC mice, cell lines, patient derived xenografts and primary human samples. We also determined that KMLC, but not EGFR-mutant (EGFR-MUT) LC, is enriched in triacylglycerides (TAG) and phosphatidylcholines (PC). We also found that KM upregulates fatty acid synthase (FASN), a rate-limiting enzyme in fatty acid (FA) synthesis promoting the synthesis of palmitate and PC. We determined that FASN is specifically required for the viability of KMLC, but not of LC harboring EGFR-MUT or wild type KRAS. Functional experiments revealed that FASN inhibition leads to ferroptosis, a reactive oxygen species (ROS)-and iron-dependent cell death. Consistently, lipidomic analysis demonstrated that FASN inhibition in KMLC leads to accumulation of PC with polyunsaturated FA (PUFA) chains, which are the substrate of ferroptosis. Integrating lipidomic, transcriptome and functional analyses, we demonstrated that FASN provides saturated (SFA) and monounsaturated FA (MUFA) that feed the Lands cycle, the main process remodeling oxidized phospholipids (PL), such as PC. Accordingly, either inhibition of FASN or suppression of the Lands cycle enzymes PLA2 and LPCAT3, promotes the intracellular accumulation of lipid peroxides and ferroptosis in KMLC bothin vitroandin vivo. Our work supports a model whereby the high oxidative stress caused by KM dictates a dependency on newly synthesized FA to repair oxidated phospholipids, establishing a targetable vulnerability. These results connect KM oncogenic signaling, FASN induction and ferroptosis, indicating that FASN inhibitors already in clinical trial in KMLC patients (NCT03808558) may be rapidly deployed as therapy for KMLC.
The potential of dynamic physiological traits in young tomato plants to predict field-yield performance
Authors: Gosa Sanbon Chaka , Koch Amit , Shenhar Itamar , Hirschberg Joseph , Zamir Dani , Moshelion Menachem 
Published: March 2021

AbstractTo address the challenge of predicting tomato yields in the field, we used whole-plant functional phenotyping to evaluate water relations under well-irrigated and drought conditions. The genotypes tested are known to exhibit variability in their yields in wet and dry fields. The examined lines included two lines with recessive mutations that affect carotenoid biosynthesis, zetaz2083and tangerinet3406, both isogenic to the processing tomato variety M82. The two mutant lines were reciprocally grafted onto M82, and multiple physiological characteristics were measured continuously, before, during and after drought treatment in the greenhouse. A comparative analysis of greenhouse and field yields showed that the whole-canopy stomatal conductance (gsc) in the morning and cumulative transpiration (CT) were strongly correlated with field measurements of total yield (TY:r2= 0.9 and 0.77, respectively) and plant vegetative weight (PW:r2= 0.6 and 0.94, respectively). Furthermore, the minimum CT during drought and the rate of recovery when irrigation was resumed were both found to predict resilience.
A novel Mycobacterium tuberculosis-specific subunit vaccine provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin
Authors: Woodworth Joshua S. , Clemmensen Helena Strand , Battey Hannah , Dijkman Karin , Lindenstrøm Thomas , Laureano Raquel Salvador , Taplitz Randy , Morgan Jeffrey , Aagaard Claus , Rosenkrands Ida , Lindestam Arlehamn Cecilia S. , Andersen Peter , Mortensen Rasmus 
Published: March 2021

ABSTRACTTuberculosis (TB) remains a global health crisis. Following encouraging clinical results of subunit vaccination and revaccination with Bacillus Calmette-Guérin (BCG), it has been suggested to combine BCG and subunit vaccines for increased efficacy. Current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study was to design a subunit vaccine that does not share antigens with BCG and explore the advantages of a BCG+subunit vaccine co-administration strategy, where the two vaccines do not cross-react. Eight protective antigens were selected to create a Mycobacterium tuberculosis (Mtb)-specific subunit vaccine, named H107. Whereas subunit vaccines with BCG-shared antigens displayed cross-reactivity to BCG in vivo in both mice and humans, H107 showed no cross-reactivity and did not inhibit BCG colonization in mice. Encouragingly, co-administering H107 with BCG (BCG+H107) led to increased adaptive immune responses against both H107 and BCG leading to improved BCG-mediated immunity. In contrast to subunit vaccines with BCG-shared antigens, ‘boosting’ BCG with H107 led to substantial expansion of clonal diversity in the T cell repertoire, and BCG+H107 co-administration conferred significantly increased Th17 responses and less differentiated CD4 T cells. CD4 T cells induced by BCG+H107 maintained functional superiority after Mtb infection, and BCG+H107 provided significantly increased long-term protection compared to both BCG and H107 alone, as well as, BCG co-administered with a subunit vaccine composed of antigens shared with BCG. Overall, we identify several advantages of combining an Mtb-specific subunit vaccine with BCG and introduce H107 as a BCG-complementing vaccine with distinctive value for co-administration with BCG.
BATL: Bayesian annotations for targeted lipidomics
Authors: Chitpin Justin G. , Surendra Anuradha , Nguyen Thao T. , Taylor Graeme P. , Xu Hongbin , Alecu Irina , Ortega Roberto , Tomlinson Julianna J. , Crawley Angela M. , McGuinty Michaeline , Schlossmacher Michael G. , Saunders-Pullman Rachel , Cuperlovic-Culf Miroslava , Bennett Steffany A.L. , Perkins Theodore J. 
Published: March 2021

AbstractMotivationBioinformatic tools capable of annotating, rapidly and reproducibly, large, targeted lipidomic datasets are limited. Specifically, few programs enable high-throughput peak assessment of liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) data acquired in either selected or multiple reaction monitoring (SRM and MRM) modes.ResultsWe present here Bayesian Annotations for Targeted Lipidomics (BATL), a Gaussian naïve Bayes classifier for targeted lipidomics that annotates peak identities according to eight features related to retention time, intensity, and peak shape. Lipid identification is achieved by modelling distributions of these eight input features across biological conditions and maximizing the joint posterior probabilities of all peak identities at a given transition. When applied to sphingolipid and glycerophosphocholine SRM datasets, we demonstrate over 95% of all peaks are rapidly and correctly identified.Availability and implementationBATL software is freely accessible online athttps://complimet.ca/batl/and is compatible with Safari, Firefox, Chrome and Edge.Supplementary informationSupplementary data are available atBioinformaticsonline.
Hubness reduction improves clustering and trajectory inference in single-cell transcriptomic data
Authors: Amblard Elise , Bac Jonathan , Chervov Alexander , Soumelis Vassili , Zinovyev Andrei 
Published: March 2021

AbstractBackgroundSingle-cell RNA-seq datasets are characterized by large ambient dimensionality, and their analyses can be affected by various manifestations of the dimensionality curse. One of these manifestations is the hubness phenomenon, i.e. existence of data points with surprisingly large incoming connectivity degree in the neighbourhood graph. Conventional approach to dampen the unwanted effects of high dimension consists in applying drastic dimensionality reduction. It remains unexplored if this step can be avoided thus retaining more information than contained in the low-dimensional projections, by correcting directly hubness.ResultsWe investigate the phenomenon of hubness in scRNA-seq data in spaces of increasing dimensionality. We also link increased hubness to increased levels of dropout in sequencing data. We show that hub cells do not represent any visible technical or biological bias. The effect of various hubness reduction methods is investigated with respect to the visualization, clustering and trajectory inference tasks in scRNA-seq datasets. We show that hubness reduction generates neighbourhood graphs with properties more suitable for applying machine learning methods; and that it outperforms other state-of-the-art methods for improving neighbourhood graphs. As a consequence, clustering, trajectory inference and visualisation perform better, especially for datasets characterized by large intrinsic dimensionality.ConclusionHubness is an important phenomenon in sequencing data. Reducing hubness can be beneficial for the analysis of scRNA-seq data with large intrinsic dimensionality in which case it can be an alternative to drastic dimensionality reduction.
A two-type branching process model of gene family evolution
Authors: Zwaenepoel Arthur , Peer Yves Van de 
Published: March 2021

AbstractPhylogenetic models of gene family evolution based on birth-death processes (BDPs) vide an awkward fit to comparative genomic data sets. A central assumption of these models is the constant per-gene loss rate in any particular family. Because of the possibility of partial functional redundancy among gene family members, gene loss dynamics are however likely to be dependent on the number of genes in a family, and different variations of commonly employed BDP models indeed suggest this is the case. We propose a simple two-type branching process model to better approximate the stochastic evolution of gene families by gene duplication and loss and perform Bayesian statistical inference of model parameters in a phylogenetic context. We evaluate the statistical methods using simulated data sets and apply the model to gene family data forDrosophila, yeasts and primates, providing new quantitative insights in the long-term maintenance of duplicated genes.
Plasma Membrane Calcium ATPase (PMCA) Regulates Stoichiometry of CD4+T-cell Compartments
Authors: Merino-Wong Maylin , Niemeyer Barbara A. , Alansary Dalia 
Published: March 2021

AbstractImmune responses involve mobilization of T cells within naïve and memory compartments. Tightly regulated Ca2+levels are essential for balanced immune outcomes. How Ca2+contributes to regulating compartment stoichiometry is unknown. Here, we show that plasma membrane Ca2+ATPase 4 (PMCA4) is differentially expressed in human CD4+T compartments yielding distinct store operated Ca2+entry (SOCE) profiles. Modulation of PMCA4 yielded a more prominent increase of SOCE in memory than in naïve CD4+T cell. Interestingly, downregulation of PMCA4 reduced the effector compartment fraction and led to accumulation of cells in the naïve compartment.In silicoanalysis and chromatin immunoprecipitation unraveled Ying Yang 1 (YY1) as a transcription factor regulating PMCA4 expression. Analyses of PMCA and YY1 expression patterns following activation and of PMCA promoter activity following downregulation of YY1 highlight repressive role of YY1 on PMCA expression. Our findings show that under the transcriptional control by YY1, PMCA4 adapts Ca2+levels to cellular requirements during effector and quiescent phases and thereby represent a potential target to intervene with the outcome of the immune response.
Evolutionary determinants of non-seasonal breeding in wild chacma baboons
Authors: Dezeure Jules , Baniel Alice , Burtschell Lugdiwine , Carter Alecia J. , Godelle Bernard , Cowlishaw Guy , Huchard Elise 
Published: March 2021

ABSTRACTAnimal reproductive phenology varies from strongly seasonal to non-seasonal, sometimes among closely related or sympatric species. While the extent of reproductive seasonality is often attributed to environmental seasonality, this fails to explain many cases of non-seasonal breeding in seasonal environments. We investigated the evolutionary determinants of non-seasonal breeding in a wild primate, the chacma baboon (Papio ursinus), living in a seasonal environment with high climatic unpredictability. We tested three hypotheses proposing that non-seasonal breeding has evolved in response to (1) climatic unpredictability, (2) reproductive competition between females favouring birth asynchrony, and (3) individual, rank-dependent variations in optimal reproductive timing. We found strong support for an effect of reproductive asynchrony modulated by rank: (i) birth synchrony is costly to subordinate females, lengthening their interbirth intervals, and (ii) females delay their reproductive timings (fertility periods and conceptions) according to other females in the group to stagger conceptions. These results indicate that reproductive competition generates reproductive asynchrony, weakening the intensity of reproductive seasonality at the population level. This study emphasizes the importance of sociality in mediating the evolution of reproductive phenology in gregarious organisms, a result of broad significance for understanding key demographic parameters driving population responses to increasing climatic fluctuations.