bluuebunny/crossref_metadata_2025_split huggingface dataset:
No-U-Turn sampling for phylogenetic trees
Authors: Wahle Johannes 
Published: March 2021

AbstractThe inference of phylogenetic trees from sequence data has become a staple in evolutionary research. Bayesian inference of such trees is predominantly based on the Metropolis-Hastings algorithm. For high dimensional and correlated data this algorithm is known to be inefficient. There are gradient based algorithms to speed up such inference. Building on recent research which uses gradient based approaches for the inference of phylogenetic trees in a Bayesian framework, I present an algorithm which is capable of performing No-U-Turn sampling for phylogenetic trees. As an extension to Hamiltonian Monte Carlo methods, No-U-Turn sampling comes with the same benefits, such as proposing distant new states with a high acceptance probability, but eliminates the need to manually tune hyper parameters. Evaluated on real data sets, the new sampler shows that it converges faster to the target distribution. The results also indicate that a higher number of topologies are traversed during sampling by the new algorithm in comparison to traditional Markov Chain Monte Carlo approaches. This new algorithm leads to a more efficient exploration of the posterior distribution of phylogenetic tree topologies.Author summaryPhylogentic trees are important for our understanding of evolutionary relationships. But even for only a small number of entities the number of possible trees is immense. In order to efficiently search through this large space and analyze the distributions of these trees, different algorithmic solutions have been proposed. A phylogenetic tree is not only defined by the way it groups the entities but also by the length of the branches. This nature of the phylogentic trees complicates the exploration of these distributions. Building on research and algorithmic ideas for non tree like data and recent developments on the mathematics of trees, I propose a new method which is able to traverse the space of possible trees more rapidly. By using a search strategy which is guided by the data and the underlying evolutionary model, the algorithm is able to better sample from the desired distribution. I am able to show that the new algorithm can indeed analyze the correct distribution but can do so with a higher efficiency than other algorithms.
Vegfr3-tdTomato, a reporter mouse for microscopic visualization of lymphatic vessel by multiple modalities
Authors: Redder Esther , Kirschnick Nils , Hägerling René , Hansmeier Nils , Kiefer Friedemann 
Published: March 2021

AbstractLymphatic vessels are indispensable for tissue fluid homeostasis, transport of solutes and dietary lipids and immune cell trafficking. In contrast to blood vessels, which are easily visible by their erythrocyte cargo, lymphatic vessels are not readily detected in the tissue context. Their invisibility interferes with the analysis of the three-dimensional lymph vessel structure in large tissue volumes and hampers dynamic intravital studies on lymphatic function and pathofunction. An approach to overcome these limitations are mouse models, which express transgenic fluorescent proteins under the control of tissue-specific promotor elements.We introduce here the BAC-transgenic mouse reporter strainVegfr3-tdTomato that expresses a membrane-tagged version of tdTomato under control of Flt4 regulatory elements.Vegfr3-tdTomato mice inherited the reporter in a mendelian fashion and showed selective and stable fluorescence in the lymphatic vessels of multiple organs tested, including lung, kidney, heart, diaphragm, intestine, mesentery and dermis. In this model, tdTomato expression was sufficient for direct visualisation of lymphatic vessels by epifluorescence microscopy. Furthermore, lymph vessels were readily visualized using a number of microscopic modalities including confocal laser scanning, light sheet fluorescence and two-photon microscopy. Due to the early onset of VEGFR-3 expression in venous embryonic vessels and the short maturation time of tdTomato, this reporter offers an interesting alternative to Prox1-promoter driven lymphatic reporter mice for instance to study the developmental differentiation of venous to lymphatic endothelial cells.
A graph-based cell tracking algorithm with few manually tunable parameters and automated segmentation error correction
Authors: Löffler Katharina , Scherr Tim , Mikut Ralf 
Published: March 2021

AbstractAutomatic cell segmentation and tracking enables to gain quantitative insights into the processes driving cell migration. To investigate new data with minimal manual effort, cell tracking algorithms should be easy to apply and reduce manual curation time by providing automatic correction of segmentation errors. Current cell tracking algorithms, however, are either easy to apply to new data sets but lack automatic segmentation error correction, or have a vast set of parameters that needs either manual tuning or annotated data for parameter tuning. In this work, we propose a tracking algorithm with only few manually tunable parameters and automatic segmentation error correction. Moreover, no training data is needed. We compare the performance of our approach to three well-performing tracking algorithms from the Cell Tracking Challenge on data sets with simulated, degraded segmentation – including false negatives, over- and under-segmentation errors. Our tracking algorithm can correct false negatives, over- and under-segmentation errors as well as a mixture of the aforementioned segmentation errors. On data sets with under-segmentation errors or a mixture of segmentation errors our approach performs best. Moreover, without requiring additional manual tuning, our approach ranks several times in the top 3 on the 6thedition of the Cell Tracking Challenge.
Growth-Rate Dependent And Nutrient-Specific Gene Expression Resource Allocation In Fission Yeast
Authors: Kleijn Istvan T. , Martínez-Segura Amalia , Bertaux François , Saint Malika , Kramer Holger , Shahrezaei Vahid , Marguerat Samuel 
Published: March 2021

ABSTRACTCellular resources are limited and their relative allocation to gene expression programmes determines physiological states and global properties such as the growth rate. Quantitative studies using various growth conditions have singled out growth rate as a major physiological variable explaining relative protein abundances. Here, we used the simple eukaryoteSchizosaccharomyces pombeto determine the importance of growth rate in explaining relative changes in protein and mRNA levels during growth on a series of non-limiting nitrogen sources. Although half of fission yeast genes were significantly correlated with the growth rate, this came alongside wide-spread nutrient-specific regulation. Proteome and transcriptome often showed coordinated regulation but with notable exceptions, such as metabolic enzymes. Genes positively correlated with growth rate participated in every level of protein production with the notable exception of RNA polymerase II, whereas those negatively correlated mainly belonged to the environmental stress response programme. Critically, metabolic enzymes, which represent ∼55-70% of the proteome by mass, showed mainly condition-specific regulation. Specifically, many enzymes involved in glycolysis and NAD-dependent metabolism as well as the fermentative and respiratory pathways were condition-dependent and not consistently correlated with growth. In summary, we provide a rich account of resource allocation to gene expression in a simple eukaryote, advancing our basic understanding of the interplay between growth-rate dependent and nutrient-specific gene expression.
OCRbayes: A Bayesian hierarchical modeling framework for Seahorse extracellular flux oxygen consumption rate data analysis
Authors: Zhang Xiang , Yuan Taolin , Keijer Jaap , de Boer Vincent C. J. 
Published: March 2021

AbstractBackgroundMitochondrial dysfunction is involved in many complex diseases. Efficient and accurate evaluation of mitochondrial functionality is crucial for understanding pathology as well as facilitating novel therapeutic developments. As a popular platform, Seahorse extracellular flux (XF) analyzer is widely used for measuring mitochondrial oxygen consumption rate (OCR) in living cells. A hidden feature of Seahorse XF OCR data is that it has a complex data structure, caused by nesting and crossing between measurement cycles, wells and plates. Surprisingly, statistical analysis of Seahorse XF data has not received sufficient attention, and current methods completely ignore the complex data structure, impairing the robustness of statistical inference.ResultsTo rigorously incorporate the complex structure into data analysis, here we developed a Bayesian hierarchical modeling framework, OCRbayes, and demonstrated its applicability based on analysis of published data sets.ConclusionsWe showed that OCRbayes can analyze Seahorse XF OCR experimental data derived from either single or multiple plates. Moreover, OCRbayes has potential to be used for diagnosing patients with mitochondrial diseases.
Timing of increased temperature sensitivity coincides with nervous system development in winter moth embryos
Authors: van Dis Natalie E. , van der Zee Maurijn , Hut Roelof A. , Wertheim Bregje , Visser Marcel E. 
Published: March 2021

AbstractClimate change is rapidly altering the environment and many species will need to genetically adapt their seasonal timing to keep up with these changes. Insect development rate is largely influenced by temperature, but we know little about the mechanisms underlying temperature sensitivity of development. Here we investigate seasonal timing of egg hatching in the winter moth, one of the few species which has been found to genetically adapt to climate change, likely through selection on temperature sensitivity of egg development rate. To study when during development winter moth embryos are most sensitive to changes in ambient temperature, we gave eggs an increase or decrease in temperature at different moments during their development. We measured their developmental progression and timing of egg hatching, and used fluorescence microscopy to construct a timeline of embryonic development for the winter moth. We found that egg development rate responded more strongly to temperature once embryos were in the fully extended germband stage. This is the phylotypic stage at which all insect embryos have developed a rudimentary nervous system. Furthermore, at this stage timing of ecdysone signaling determines developmental progression, which could act as an environment dependent gateway. Intriguingly, this may suggest that, from the phylotypic stage onward, insect embryos can start to integrate internal and environmental stimuli to actively regulate important developmental processes. As we found evidence that there is genetic variation for temperature sensitivity of egg development rate in our study population, such regulation could be a target of selection imposed by climate change.
Metagenomic analysis reveals the signature of gut microbiota associated with human chronotypes
Authors: Carasso Shaqed , Fishman Bettina , Lask Liel Stelmach , Shochat Tamar , Geva-Zatorsky Naama , Tauber Eran 
Published: March 2021

AbstractPatterns of diurnal activity differ substantially between individuals, with early risers and late sleepers being examples of opposite chronotypes. Growing evidence suggests that the late chronotype significantly impacts the risk of developing mood disorders, obesity, diabetes, and other chronic diseases. Despite the vast potential of utilizing chronotype information for precision medicine, those factors that shape chronotypes remain poorly understood. Here, we assessed whether the various chronotypes are associated with different gut microbiome compositions. Using metagenomic sequencing analysis, we established a distinct signature associated with chronotype based on two bacterial genera,Alistipes(elevated in “larks”) andLachnospira(elevated in “owls”). We identified three metabolic pathways associated with the early chronotype, and linked distinct dietary patterns with different chronotypes. Our work demonstrates an association between the gut microbiome and chronotype and may represent the first step towards developing dietary interventions aimed at ameliorating the deleterious health correlates of the late chronotype.
DNA spike-ins enable confident interpretation of SARS-CoV-2 genomic data from amplicon-based sequencing
Authors: Lagerborg Kim A. , Normandin Erica , Bauer Matthew R. , Adams Gordon , Figueroa Katherine , Loreth Christine , Gladden-Young Adrianne , Shaw Bennett , Pearlman Leah , Shenoy Erica S. , Hooper David , Pierce Virginia M. , Zachary Kimon C. , Park Daniel J. , MacInnis Bronwyn L. , Lemieux Jacob E. , Sabeti Pardis C. , Reilly Steven K , Siddle Katherine J. 
Published: March 2021

AbstractThe rapid global spread and continued evolution of SARS-CoV-2 has highlighted an unprecedented need for viral genomic surveillance and clinical viral sequencing. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine lab processes and results. This challenge will only increase with expanding global production of sequences by diverse research groups for epidemiological and clinical interpretation. We present an approach which uses synthetic DNA spike-ins (SDSIs) to track samples and detect inter-sample contamination through a sequencing workflow. Applying this approach to the ARTIC Consortium’s amplicon design, we define a series of best practices for Illumina-based sequencing and provide a detailed characterization of approaches to increase sensitivity for low-viral load samples incorporating the SDSIs. We demonstrate the utility and efficiency of the SDSI method amidst a real-time investigation of a suspected hospital cluster of SARS-CoV-2 cases.
Persistent ventricle partitioning in the adult zebrafish heart
Authors: Pfefferli Catherine , Moran Hannah R. , Felker Anastasia , Mosimann Christian , Jaźwińska Anna 
Published: March 2021

AbstractThe vertebrate heart integrates cells from the early-differentiating first heart field (FHF) and the later-differentiating second heart field (SHF) emerging from the lateral plate mesoderm. In mammals, this process forms the basis for the development of the left and right ventricle chambers and subsequent chamber septation. The single ventricle-forming zebrafish heart also integrates FHF and SHF lineages during embryogenesis, yet the contributions of these two myocardial lineages to the adult zebrafish heart remain incompletely understood. Here, we characterize the myocardial labeling of FHF descendants in both the developing and adult zebrafish ventricle. Expanding previous findings, late gastrulation-stage labeling usingdrl-driven CreERT2 recombinase with a myocardium-specific,myl7-controlledloxPreporter results in predominant labeling of FHF-derived outer curvature and the right side of the embryonic ventricle. Raised to adulthood, such lineage-labeled hearts retain broad areas of FHF cardiomyocytes in a region of the ventricle that is positioned at the opposite side to the atrium and encompasses the apex. Our data add to the increasing evidence for a persisting cell-based compartmentalization of the adult zebrafish ventricle even in the absence of any physical boundary.
Binary interactome models of inner- versus outer-complexome organisation
Authors: Lambourne Luke , Yadav Anupama , Wang Yang , Desbuleux Alice , Kim Dae-Kyum , Cafarelli Tiziana , Pons Carles , Kovács István A. , Jailkhani Noor , Schlabach Sadie , Ridder David De , Luck Katja , Bian Wenting , Shen Yun , Yang Zhipeng , Mee Miles W. , Helmy Mohamed , Jacob Yves , Lemmens Irma , Rolland Thomas , Coté Atina G. , Gebbia Marinella , Kishore Nishka , Knapp Jennifer J. , Mellor Joseph C. , Reimand Jüri , Tavernier Jan , Cusick Michael E. , Falter-Braun Pascal , Spirohn Kerstin , Zhong Quan , Aloy Patrick , Hao Tong , Charloteaux Benoit , Roth Frederick P. , Hill David E. , Calderwood Michael A. , Twizere Jean-Claude , Vidal Marc 
Published: March 2021

SummaryHundreds of different protein complexes that perform important functions across all cellular processes, collectively comprising the “complexome” of an organism, have been identified1. However, less is known about the fraction of the interactome that exists outside the complexome, in the “outer-complexome”. To investigate features of “inner”- versus outer-complexome organisation in yeast, we generated a high-quality atlas of binary protein-protein interactions (PPIs), combining three previous maps2–4and a new reference all-by-all binary interactome map. A greater proportion of interactions in our map are in the outer-complexome, in comparison to those found by affinity purification followed by mass spectrometry5–7or in literature curated datasets8–11. In addition, recent advances in deep learning predictions of PPI structures12mirror the existing experimentally resolved structures in being largely focused on the inner complexome and missing most interactions in the outer-complexome. Our new PPI network suggests that the outer-complexome contains considerably more PPIs than the inner-complexome, and integration with functional similarity networks13–15reveals that interactions in the inner-complexome are highly detectable and correspond to pairs of proteins with high functional similarity, while proteins connected by more transient, harder-to-detect interactions in the outer-complexome, exhibit higher functional heterogeneity.
Cis-regulatory variants affect gene expression dynamics in yeast
Authors: Shih Ching-Hua , Fay Justin C. 
Published: March 2021

AbstractEvolution ofcis-regulatory sequences depends on how they effect gene expression and motivates both the identification and prediction ofcis-regulatory variants responsible for expression differences within and between species. While much progress has been made in relatingcis-regulatory variants to expression levels, the timing of gene activation and repression may also be important to the evolution ofcis-regulatory sequences. We investigated allele-specific expression (ASE) dynamics within and betweenSaccharomycesspecies during the diauxic shift and found appreciablecis-acting variation in gene expression dynamics. Within species ASE is associated with intergenic variants, but ASE dynamics are more strongly associated with insertions and deletions than ASE levels. To refine these associations we used a high-throughput reporter assay to test promoter regions and individual variants. Within the subset of regions that recapitulated endogenous expression we identified and characterizedcis-regulatory variants that affect expression dynamics. Between species, chimeric promoter regions generate novel patterns and indicate constraints on the evolution of gene expression dynamics. We conclude that changes incis-regulatory sequences can tune gene expression dynamics and that the interplay between expression dynamics and other aspects expression are relevant to the evolution ofcis-regulatory sequences.
An egg-derived sulfated N-Acetyllactosamine glycan is an antigenic decoy of influenza virus vaccines
Authors: Guthmiller Jenna J. , Utset Henry A. , Henry Carole , Li Lei , Zheng Nai-Ying , Sun Weina , Vieira Marcos Costa , Zost Seth , Huang Min , Hensley Scott E. , Cobey Sarah , Palese Peter , Wilson Patrick C. 
Published: March 2021

AbstractInfluenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess differential glycosylation patterns than viruses circulating amongst humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived sulfated N-acetyllactosamine (LacNAc) that is an antigenic decoy. Half of subjects that received an egg-grown vaccine mounted an antibody response against this egg-derived antigen. Egg-binding monoclonal antibodies specifically bind viruses grown in eggs, but not viruses grown in other chicken derived cells, suggesting only egg-grown vaccines can induce anti-LacNAc antibodies. Notably, antibodies against the sulfated LacNAc utilized a restricted antibody repertoire and possessed features of natural antibodies, as most antibodies were IgM and have simple heavy chain complementarity determining region 3. By analyzing a public dataset of influenza virus vaccine induced plasmablasts, we discovered egg-binding public clonotypes that were shared across studies. Together, this study shows that egg-grown vaccines can induce antibodies against an egg-associated glycan, which may divert the host immune response away from protective epitopes.
Understanding C4photosynthesis in Setaria by a proteomic and kinetic approach
Authors: Calace Paula , Tonetti Tomás , Margarit Ezequiel , Figueroa Carlos M. , Lobertti Carlos , Andreo Carlos S. , Wheeler Mariel C. Gerrard , Saigo Mariana 
Published: March 2021

AbstractPlants performing C4photosynthesis have a higher productivity per crop area related to an optimized use of water and nutrients. This is achieved through a series of anatomical and biochemical features that allow the concentration of CO2around RuBisCO. In C4plants the photosynthetic reactions are distributed between two cell types, they initially fix the carbon to C4acids within the mesophyll cells (M) and then transport these compounds to the bundle sheath cells (BS), where they are decarboxylated so that the resulting CO2is incorporated into the Calvin cycle (CC).This work is focused on the comparative analysis of the proteins present in M and BS ofSetaria viridis, a C4model close relative of several major feed, fuel, and bioenergy grasses. The integration of kinetic and proteomic approaches agrees that the C4compound malate is mainly decarboxylated in the chloroplasts of BS cells by NADP-malic enzyme (NADP-ME). Besides, NAD-malic enzyme (NAD-ME) located in the mitochondria could also contribute to the C4carbon shuttle. We presented evidence of metabolic strategies that involve chloroplastic, mitochondrial and peroxisomal proteins to avoid the leakage of C4intermediates in order to sustain an efficient photosynthetic performance.HighlightProteomic and kinetic analyses show metabolic strategies involving chloroplastic, mitochondrial and peroxisomal proteins to maintain the C4cycle performance in parallel to other metabolic pathways.
A novel, open source, low-cost bioreactor for load-controlled cyclic loading of tendon explants
Authors: Pedaprolu Krishna , Szczesny Spencer E 
Published: March 2021

AbstractA major risk factor for tendinopathy is tendon overuse (i.e., fatigue loading). Fatigue loading of tendon damages the extracellular matrix and induces tissue degeneration. However, the specific mechanisms linking tendon fatigue damage with tissue degeneration are unclear. While explant models of tendon fatigue loading have been used to address this knowledge gap, they predominantly employ bioreactors that apply cyclic displacements/strains rather than loads/stresses, which are more physiologically relevant. This is because of the technical complexity and cost of building a load-controlled bioreactor, which requires multiple motors, load cells, and computationally intensive feedback loops. Here, we present a novel, low-cost, load-controlled bioreactor that applies cyclic loading to multiple tendon explants by offloading weights from a single motorized stage. Using an optional load cell, we validated that the bioreactor can effectively provide load-controlled fatigue testing of mouse and rat tendon explants while maintaining tissue viability. Furthermore, all the design files, bill of materials, and operating software are available “open source” (https://github.com/Szczesnytendon/Bioreactor) so that anyone can easily manufacture and use the bioreactor for their own research. Therefore, this novel load-controlled bioreactor will enable researchers to study the mechanisms driving fatigue-induced tendon degeneration in a more physiologically relevant and cost-effective manner.