bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subfunctionalization of paralog transcription factors contributes to regulation of alkaloid pathway branch choice inCatharanthus roseus
Authors: Colinas Maite , Pollier Jacob , Vaneechoutte Dries , Malat Deniz G. , Schweizer Fabian , De Milde Liesbeth , De Clercq Rebecca , Guedes Joana G. , Martínez-Cortés Teresa , Molina Hidalgo Francisco J. , Sottomayor Mariana , Vandepoele Klaas , Goossens Alain 
Published: May 2020

SUMMARYCatharanthus roseusproduces a diverse range of specialized metabolites of the monoterpenoid indole alkaloid (MIA) class in a heavily branched pathway. Recent great progress in identification of MIA biosynthesis genes revealed that the different pathway branch genes are expressed in a highly cell type- and organ-specific and stress-dependent manner. This implies a complex control by specific transcription factors (TFs), only partly revealed today. We generated and mined a comprehensive compendium of publicly availableC. roseustranscriptome data for MIA pathway branch-specific TFs. Functional analysis was performed through extensive comparative gene expression analysis and profiling of over 40 MIA metabolites in theC. roseusflower petal expression system. We identified additional members of the known BIS and ORCA regulators. Further detailed study of the ORCA TFs suggests subfunctionalization of ORCA paralogs in terms of target gene-specific regulation and synergistic activity with the central jasmonate response regulator MYC2. Moreover, we identified specific amino acid residues within the ORCA DNA-binding domains that contribute to the differential regulation of some MIA pathway branches. Our results advance our understanding of TF paralog specificity for which, despite the common occurrence of closely related paralogs in many species, comparative studies are scarce.SIGNIFICANCE STATEMENTA gene discovery program for regulators of monoterpenoid indole alkaloid biosynthesis inCatharanthus roseusadvances our understanding of paralog specificity and subfunctionalization of the renowned class of ORCA transcription factors, particularly in terms of target gene-specificity and synergistic activity with other jasmonate-responsive transcription factors.
A theoretical framework to study the influence of electrical fields on mesenchymal stem cells
Authors: Dawson Jonathan , Lee Poh Soo , van Rienen Ursula , Appali Revathi 
Published: May 2020

ABSTRACTMesenchymal stem cell dynamics involves cell proliferation and cell differentiation into cells of distinct functional type, such as osteoblasts, adipocytes, or chondrocytes. Electrically active implants influence these dynamics for the regeneration of the cells in damaged tissues. How applied electric field influences processes of individual stem cells is a problem mostly unaddressed. The mathematical approaches to study stem cell dynamics have focused on the stem cell population as a whole, without resolving individual cells and intracellular processes. In this paper, we present a theoretical framework to describe the dynamics of a population of stem cells, taking into account the processes of the individual cells. We study the influence of the applied electric field on the cellular processes. We test our mean-field theory with the experiments from the literature, involvingin vitroelectrical stimulation of stem cells. We show that a simple model can quantitatively describe the experimentally observed time-course behavior of the total number of cells and the total alkaline phosphate activity in a population of mesenchymal stem cells. Our results show that the stem cell differentiation rate is dependent on the applied electrical field, confirming published experimental findings. Moreover, our analysis supports the cell density-dependent proliferation rate. Since the experimental results are averaged over many cells, our theoretical framework presents a robust and sensitive method for determining the effect of applied electric fields at the scale of the individual cell. These results indicate that the electric field stimulation may be effective in promoting bone regeneration by accelerating osteogenic differentiation.
Independent and Interacting Value Systems for Reward and Information in the Human Brain
Authors: Dezza I. Cogliati , Cleeremens A. , Alexander W. 
Published: May 2020

ABSTRACTTheories of Prefrontal Cortex (PFC) as optimizingrewardvalue have been widely deployed to explain its activity in a diverse range of contexts, with substantial empirical support in neuroeconomics and decision neuroscience. Theoretical frameworks of brain function, however, suggest the existence of a second, independent value system for optimizinginformationduring decision-making. To date, however, there has been little direct empirical evidence in favor of such frameworks. Here, by using computational modeling, model-based fMRI analysis, and a novel experimental paradigm, we aim at establishing whether independent value systems exist in human PFC. We identify two regions in the human PFC which independently encode distinct value signals. These value signals are then combined in subcortical regions in order to implement choices. Our results provide empirical evidence for PFC as an optimizer of independent value signals during decision-making under realistic scenarios, with potential implications for the interpretation of PFC activity in both healthy and clinical population.One Sentence SummaryReward and information value are independently optimized in the Human PFC and are then combined in subcortical regions in order to implement choices.
Impact of formate supplementation on body weight and plasma amino acids
Authors: Dhayade Sandeep , Pietzke Matthias , Wiesheu Robert , Tait-Mulder Jacqueline , Athineos Dimitris , Sumpton David , Coffelt Seth B. , Blyth Karen , Vazquez Alexei 
Published: May 2020

AbstractCurrent nutritional recommendations are focused on energy, fat, carbohydrate, protein and vitamins. Less attention has been paid to the nutritional demand of one-carbon units for nucleotide and methionine synthesis. Here we investigate the impact of sodium formate supplementation as a nutritional intervention to increase the dietary intake of one-carbon units. A cohort of six female and six male mice received 125 mM sodium formate in the drinking water for three months. A control group of another six female and six male mice was also followed up for the same period of time. Tail vein blood samples were collected once a month and profiled with a haematology Analyser. At the end of the study blood and tissues were collected for metabolomics analysis and immune cell sorting. Formate supplementation has no significant physiological effect on male mice. Formate supplementation has no significant effect on the immune cell counts during the intervention or at the end of the study in either gender. In female mice however, the body weight and spleen wet-weight were significantly increased by formate supplementation, while the blood plasma levels of amino acids were decreased. Formate supplementation also increased the frequency of probiotic bacteria in the stools of female mice. We conclude that formate supplementation induces physiological changes in female mice.
Spontaneous network coupling enables efficient task performance without local task-induced activations
Authors: Allaman Leslie , Mottaz Anaïs , Kleinschmidt Andreas , Guggisberg Adrian G. 
Published: May 2020

AbstractNeurobehavioral studies in humans have long concentrated on changes in local activity levels during repetitive executions of a task. Spontaneous neural coupling within extended networks has latterly been found to also influence performance. Here, we intend to uncover the underlying mechanisms and the interaction with task-induced activations. We demonstrate that high performers in visual perception and motor sequence tasks present an absence of classical task-induced activations, but, instead, strong spontaneous network coupling. Activations were thus a compensation mechanism needed only in subjects with lower spontaneous network interactions. This challenges classical models of neural processing and calls for new strategies in attempts to train and enhance performance.
The Digital Mouse: why computational modelling of mouse models of disease can improve translation
Authors: van Riel Natal , Müller Ralph , Dall’Ara Enrico 
Published: May 2020

AbstractComputational models can be used to study the mechanistic phenomena of disease. Current mechanistic computer simulation models mainly focus on (patho)physiology in humans. However, often data and experimental findings from preclinical studies are used as input to develop such models. Biological processes underlying age-related chronic diseases are studied in animal models. The translation of these observations to clinical applications is not trivial. As part of a group of international scientists working in the COST Action network MouseAGE, we argue that in order to boost the translation of pre-clinical research we need to develop accuratein silicocounterparts of thein vivoanimal models. The Digital Mouse is proposed as framework to support the development of evidence-based medicine, for example to develop geroprotectors, which are drugs that target fundamental mechanisms of ageing.HighlightsComputational modelling of human (patho)physiology is advancing rapidly, often using and extrapolating experimental findings from preclinical disease models.The lack ofin silicomodels to supportin vivomodelling in mice is a missing link in current approaches to study complex, chronic diseases.The development of mechanistic computational models to simulate disease in mice can boost the discovery of novel therapeutic interventions.The ‘Digital Mouse’ is proposed as a framework to implement this ambition. The development of a Digital Mouse Frailty Index (DM:FI) to study aging and age-related diseases is provided as an example.
An agent-based model clarifies the importance of functional and developmental integration in shaping brain evolution
Authors: Avin Shahar , Currie Adrian , Montgomery Stephen H. 
Published: May 2020

AbstractComparisons of vertebrate brain structure suggest a conserved pattern of scaling between components, but also many examples of lineages diverging dramatically from these general trends. Two competing hypotheses of brain evolution seek to explain these patterns of variation by invoking either ‘external’ processes, such as selection driving phenotypic change, or ‘internal’ processes, like developmental coupling among brain regions. Efforts to reconcile these views remain deadlocked, in part due to empirical under-determination and the limitations of ‘relative significance’ debates. We introduce an agent-based model that allows us to simulate brain evolution in a ‘bare-bones’ system and examine the dependencies between variables that may shape brain evolution. Our simulations formalise verbal arguments and interpretations concerning the evolution of brain structure. We illustrate that ‘concerted’ patterns of brain evolution cannot alone be taken as evidence for developmental coupling, or constraint, despite these terms often being treated as synonymous in the literature. Both developmentally coupled and uncoupled brain architectures can represent adaptive mechanisms, depending on the distribution of selection across the brain, life history, and the relative costs of neural tissue. Our model also illustrates how the prevalence of mosaic and concerted patterns of evolution may fluctuate through time in a variable environment, which we argue implies that developmental coupling is unlikely to be a significant evolutionary constraint.
LAMA: Automated image analysis for developmental phenotyping of mouse embryos
Authors: Horner Neil R. , Venkataraman Shanmugasundaram , Casero Ramón , Brown James M. , Johnson Sara , Teboul Lydia , Wells Sara , Brown Steve , Westerberg Henrik , Mallon Ann-Marie 
Published: May 2020

AbstractAdvanced 3D imaging modalities such as micro computed tomography (micro-CT), high resolution episcopic microscopy (HREM), and optical projection tomography (OPT) have been readily incorporated into high-throughput phenotyping pipelines, such as the International Mouse Phenotyping Consortium (IMPC). Such modalities generate large volumes of raw data that cannot be immediately harnessed without significant resources of manpower and expertise. Thus, rapid automated analysis and annotation is critical to ensure that 3D imaging data is able to be integrated with other multi-dimensional phenotyping data. To this end, we present an automated computational mouse phenotyping pipeline called LAMA, based on image registration, which requires minimal technical expertise and human input to use. Designed predominantly for developmental biologists, our software performs image pre-processing, registration, statistical and gene function annotation, and segmentation of 3D micro-CT data. We address several limitations of current methods and create an easy to use, fast solution application for mouse embryo phenotyping. We also present a highly granular, novel anatomical E14.5 (14.5 days post coitus) atlas of a population average that integrates with our pipeline to allow a range of dysmorphologies to be automatically annotated as well as results from the validation of the pipeline.
Global mapping ofSalmonella enterica-host protein-protein interactions during infection
Authors: Walch Philipp , Selkrig Joel , Knodler Leigh A. , Rettel Mandy , Stein Frank , Fernandez Keith , Viéitez Cristina , Potel Clément M. , Scholzen Karoline , Geyer Matthias , Rottner Klemens , Steele-Mortimer Olivia , Savitski Mikhail M. , Holden David W. , Typas Athanasios 
Published: May 2020

SummaryIntracellular bacterial pathogens inject effector proteins into host cells to hijack diverse cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32Salmonella entericaserovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effector proteins, and quantified PPIs in macrophages and epithelial cells by Affinity-Purification Quantitative Mass-Spectrometry. Thereby, we identified 25 previously described and 421 novel effector-host PPIs. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. Using reciprocal co-immunoprecipitations, we validated 13 out of 22 new PPIs. We then used this host-pathogen physical interactome resource to demonstrate that SseJ and SseL collaborate in redirecting cholesterol to theSalmonellaContaining Vacuole (SCV) via NPC1, PipB directly recruits the organelle contact site protein PDZD8 to the SCV, and SteC promotes actin bundling by directly phosphorylating formin-like proteins.
The UCSC SARS-CoV-2 Genome Browser
Authors: Fernandes Jason D. , Hinrichs Angie S. , Clawson Hiram , Navarro Gonzalez Jairo , Lee Brian T. , Nassar Luis R. , Raney Brian J. , Rosenbloom Kate R. , Nerli Santrupti , Rao Arjun , Schmelter Daniel , Zweig Ann S. , Lowe Todd M. , Ares Manuel , Corbet-Detig Russ , Kent W. James , Haussler David , Haeussler Maximilian 
Published: May 2020

ABSTRACTBackgroundResearchers are generating molecular data pertaining to the SARS-CoV-2 RNA genome and its proteins at an unprecedented rate during the COVID-19 pandemic. As a result, there is a critical need for rapid and continuously updated access to the latest molecular data in a format in which all data can be quickly cross-referenced and compared. We adapted our genome browser visualization tool to the viral genome for this purpose. Molecular data, curated from published studies or from database submissions, are mapped to the viral genome and grouped together into “annotation tracks” where they can be visualized along the linear map of the viral genome sequence and programmatically downloaded in standard format for analysis.ResultsThe UCSC Genome Browser for SARS-CoV-2 (https://genome.ucsc.edu/covid19.html) provides continuously updated access to the mutations in the many thousands of SARS-CoV-2 genomes deposited in GISAID and the international nucleotide sequencing databases, displayed alongside phylogenetic trees. These data are augmented with alignments of bat, pangolin, and other animal and human coronavirus genomes, including per-base evolutionary rate analysis. All available annotations are cross-referenced on the virus genome, including those from major databases (PDB, RFAM, IEDB, UniProt) as well as up-to-date individual results from preprints. Annotated data include predicted and validated immune epitopes, promising antibodies, RT-PCR and sequencing primers, CRISPR guides (from research, diagnostics, vaccines, and therapies), and points of interaction between human and viral genes. As a community resource, any user can add manual annotations which are quality checked and shared publicly on the browser the next day.ConclusionsWe invite all investigators to contribute additional data and annotations to this resource to accelerate research and development activities globally. Contact us atgenome-www@soe.ucsc.eduwith data suggestions or requests for support for adding data. Rapid sharing of data will accelerate SARS-CoV-2 research, especially when researchers take time to integrate their data with those from other labs on a widely-used community browser platform with standardized machine-readable data formats, such as the SARS-CoV-2 Genome Browser.
Phosphorylation and dephosphorylation of Ser852 and Ser889 control clustering, localization, and function of PAR-3
Authors: Yamashita Kazunari , Mizuno Keiko , Furukawa Kana , Hirose Hiroko , Sakurai Natsuki , Masuda-Hirata Maki , Amano Yoshiko , Hirose Tomonori , Suzuki Atsushi , Ohno Shigeo 
Published: May 2020

AbstractCell polarity is essential for various asymmetric cellular events, where the partitioning defective (PAR) protein, PAR3, plays a unique role as a cellular landmark to establish polarity. In epithelial cells, PAR3 localizes at the subapical border such as the tight junction in vertebrates and functions as an apical determinant. Although there is much information about the regulators of PAR3 localization, the mechanism involved in PAR3 concentration and localization to the specific membrane domain remains an important question to be clarified. In this study, we demonstrate that ASPP2, a stimulator of PAR3 localization, can link PAR3 and protein phosphatase 1 (PP1). The ASPP2–PP1 complex dephosphorylates a novel phosphorylation site, Ser852, of PAR3. Furthermore, Ser852- or Ser889-unphosphorylatable PAR3 mutants form protein clusters and ectopically localize to the lateral membrane. Concomitance of clustering and ectopic localization suggests that PAR3 localization is a consequence of local clustering. We also demonstrate that unphosphorylatable forms of PAR3 are static in molecular turnover and fail to coordinate rapid reconstruction of the tight junction, supporting that both phosphorylated and dephosphorylated states are essential for the functional integrity of PAR3.Summary statementWe show that phosphorylation and dephosphorylation regulate clustering of PAR-3, a cell polarity-regulating factor, and how the clustering regulation affects localization of PAR-3 and cell-cell junction formation.
Effects of evolution on niche displacement and emergent population properties, a discussion on optimality
Authors: Rohr Rudolf P. , Loeuille Nicolas 
Published: May 2020

AbstractUnderstanding the effects of evolution on emergent population properties such as intrinsic growth rate, species abundance, or dynamical resilience is not only a key theoretical question, but has major empirical implications for conservation, agroecology, invasion ecology among others. In particular, could we classify evolutionary scenarios leading to optimisation of those properties, from the ones who do not. First, we uncover two classes of invasion fitness functions, only the first one allowing optimization of some (but typically not all) population properties. Second, we showed that our two classes are also strongly linked to niche displacement and emergence of polymorphism. Our results indicate that optimization is, in general, incompatible with niche differentiation and, therefore, with emergence of polymorphism through evolutionary branching. Actually, niche displacement between resident and mutant morphs, and potentially polymorphism, only arise when we do not expect optimality to hold. We extensively discuss which biological traits can fall into which class of invasion fitness. Although, it is possible to find traits for which optimality is expected, we argue that for the majority of the cases it does not hold. Finally, we provide practical applications of our results in conservation, agroecology, harvesting and invasion ecology.
A functional genetic toolbox for human tissue-derived organoids
Authors: Sun Dawei , Evans Lewis , Lim Kyungtae , Rawlins Emma L. 
Published: May 2020

AbstractHuman organoid systems recapitulate key features of organs offering platforms for modelling developmental biology and disease. Tissue-derived organoids have been widely used to study the impact of extrinsic niche factors on stem cells. However, they are rarely used to study endogenous gene function due to the lack of efficient gene manipulation tools. We have systematically developed and optimised a complete genetic toolbox for tissue-derived organoids. This includes “Organoid Easytag”, our efficient workflow for targeting all types of gene loci through CRISPR-mediated homologous recombination followed by flow cytometry for enriching correctly-targeted cells. Our toolbox also incorporates conditional gene knock-down, or overexpression, using tightly-inducible CRISPR interference and CRISPR activation; the first efficient application of these techniques to tissue-derived organoids. These tools will facilitate gene perturbation studies in tissue-derived organoids providing a functional counter-part to many on-going descriptive studies, such as the Human Cell Atlas Project.
Nothing better to do? Environment quality and the evolution of cooperation by partner choice
Authors: Ecoffet Paul , Bredeche Nicolas , André Jean-Baptiste 
Published: May 2020

AbstractThe effects of partner choice have been documented in a large number of biological systems such as sexual markets, interspecific mutualisms, or human cooperation. There are, however, a number of situations in which one would expect this mechanism to play a role, but where no such effect has ever been demonstrated. This is the case in particular in many intraspecific interactions, such as collective hunts, in non-human animals. Here we use individual-based simulations to solve this apparent paradox. We show that the conditions for partner choice to operate are in fact restrictive. They entail that individuals can compare social opportunities and choose the best. The challenge is that social opportunities are often rare because they necessitate the co-occurrence of (i) at least one available partner, and (ii) a resource to exploit together with this partner. This has three consequences. First, partner choice cannot lead to the evolution of cooperation when resources are scarce, which explains that this mechanism could never be observed in many cases of intraspecific cooperation in animals. Second, partner choice can operate when partners constitute in themselves a resource, which is the case in sexual interactions and interspecific mutualisms. Third, partner choice can lead to the evolution of cooperation when individuals live in a rich environment, and/or when they are highly efficient at extracting resources from their environment.