bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gds1 interacts with NuA4 to promote H4 acetylation at ribosomal protein genes
Authors: Joo Yoo Jin , Buratowski Stephen 
Published: July 2021

AbstractIn our previously published studies, RNA polymerase II transcription initiation complexes were assembled from yeast nuclear extracts onto immobilized transcription templates and analyzed by quantitative mass spectrometry. In addition to the expected basal factors and coactivators, we discovered that the uncharacterized protein Gds1 showed activator-stimulated association with promoter DNA. Gds1 co-precipitated with the histone H4 acetyltransferase NuA4, and its levels often tracked with NuA4 in immobilized template experiments. GDS1 deletion led to reduction in H4 acetylation in vivo and other phenotypes consistent with partial loss of NuA4 activity. Genome-wide chromatin immunoprecipitation revealed that the reduction in H4 acetylation was strongest at ribosomal protein gene promoters and other genes with high NuA4 occupancy. Therefore, while Gds1 is not a stoichiometric subunit of NuA4, we propose that it interacts with and modulates NuA4 in specific promoter contexts. Gds1 has no obvious metazoan homolog, but structural predictions suggest it may be distantly related to the DEK protein.
Data-driven multiscale dynamical framework to control a pandemic evolution with non-pharmaceutical interventions
Authors: Reingruber Jürgen , Papale Andrea , Ruckly Stéphane , Timsit Jean-Francois , Holcman David 
Published: July 2021

AbstractBefore the availability of vaccines, many countries have resorted multiple times to drastic social restrictions to prevent saturation of their health care system, and to regain control over an otherwise exponentially increasing COVID-19 pandemic. With the advent of data-sharing, computational approaches are key to efficiently control a pandemic with non-pharmaceutical interventions (NPIs). Here we develop a data-driven computational framework based on a time discrete and age-stratified compartmental model to control a pandemic evolution inside and outside hospitals in a constantly changing environment with NPIs. Besides the calendrical time, we introduce a second time-scale for the infection history, which allows for non-exponential transition probabilities. We develop inference methods and feedback procedures to successively recalibrate model parameters as new data becomes available. As a showcase, we calibrate the framework to study the pandemic evolution inside and outside hospitals in France until February 2021. We combine national hospitalization statistics from governmental websites with clinical data from a single hospital to calibrate hospitalization parameters. We infer changes in social contact matrices as a function of NPIs from positive testing and new hospitalization data. We use simulations to infer hidden pandemic properties such as the fraction of infected population, the hospitalisation probability, or the infection fatality ratio. We show how reproduction numbers and herd immunity levels depend on the underlying social dynamics.
An efficient method of evaluating multiple concurrent management actions on invasive populations
Authors: Davis Amy J. , Farrar Randy , Jump Brad , Hall Parker , Guerrant Travis , Pepin Kim M. 
Published: July 2021

ABSTRACTEvaluation of the efficacy of management actions to control invasive species is crucial for maintaining funding and to provide feedback for the continual improvement of management efficiency. However, it is often difficult to assess the efficacy of control methods due to limited resources for monitoring. Many managers view effort on monitoring as effort taken away from performing management actions. We developed a method to estimate invasive species abundance, evaluate management effectiveness, and evaluate population growth overtime from a combination of removal activities (e.g., aerial gunning, trapping, ground shooting) using only data collected during removal efforts (the method of removal, the date, location, number of animals removed, and the effort). This dynamic approach allows for estimating abundance at discrete time points and the estimation of population growth between removal periods. We applied this method to removal data from Mingo National Wildlife Refuge in Missouri from December 2015 to September 2019, where the management objective is elimination. Populations of feral swine on Mingo NWR have fluctuated over time but showed more marked declines in the last 3-6 months of the time series. More dramatic declines were observed in the center of the refuge likely aided by reducing potential immigration from the rest of the refuge. To counteract population growth (from both births and immigration) the percent of the population of feral swine removed monthly must be greater than the growth rate. On average, we found that removing 10% of the population monthly had only a 50% chance of causing a population decline, whereas removing 15% of the population monthly had a 95% chance of causing a population decline. Our method provides advancement over traditional removal modeling approaches because it can be applied to evaluate management programs that use a broad range of removal techniques concurrently and whose management effort and spatial coverage vary across time.
Active Cell Divisions Generate Exotic Fourfold Orientationally Ordered Phase in Living Tissue
Authors: Cislo Dillon , Qin Haodong , Yang Fengshuo , Bowick Mark J. , Streichan Sebastian J. 
Published: July 2021

AbstractMorphogenesis, the process through which genes generate form, establishes tissue scale order as a template for constructing the complex shapes of the body plan. The extensive growth required to build these ordered substrates is fuelled by cell proliferation, which, naively, should destroy order. The active mechanisms that couple cellular and physical processes to generate and maintain global order, thereby reconciling this seeming contradiction, remain elusive. Using live imaging and tissue cartography, we quantitatively analyze the dynamics of fourfold tissue ordering in the crustaceanParhyale hawaiensis. We show that cell divisions are the main drivers of tissue flow leading to a fourfold orientationally ordered phase. Waves of anisotropic cell proliferation propagate across the embryo with precise choreography, such that defects introduced into the nascent lattice by cell divisions are healed by subsequent divisions through active defect climb. Orchestrating cell proliferation rates and orientations enables cell divisions to organize, rather than fluidize, the tissue. The result is a robust, active mechanism for generating global orientational order in a non-equilibrium system that sets the stage for the subsequent development of shape and form.
Solution NMR and racemic crystallography provide insights into a novel structural class of cyclic plant peptides
Authors: Payne Colton D. , Vadlamani Grishma , Hajiaghaalipour Fatemeh , Muhammad Taj , Fisher Mark F. , Andersson Håkan S. , Göransson Ulf , Clark Richard J. , Bond Charles S. , Mylne Joshua S. , Rosengren K. Johan 
Published: July 2021

AbstractHead-to-tail cyclic and disulfide-rich peptides are natural products with applications in drug design. Among these are the PawS-Derived Peptides (PDPs) produced in seeds of the daisy plant family. PDP-23 is a unique member of this class in that it is twice the typical size and adopts two β-hairpins separated by a hinge region. The β-hairpins - both stabilised by a single disulfide bond - fold together into a V-shaped tertiary structure creating a hydrophobic core. In water two PDP-23 molecules merge their hydrophobic cores to form a square prism quaternary structure. Here, we synthesised PDP-23 and its enantiomer comprising all D-amino acids, which allowed us to confirm these solution NMR structural data by racemic crystallography. Furthermore, we discovered the related PDP-24. NMR analysis showed that PDP-24 does not form a dimeric structure and it has poor water solubility, but in less polar solvents adopts near identical secondary and tertiary structure to PDP-23. The natural role of these peptides in plants remains enigmatic, as we did not observe any antimicrobial or insecticidal activity. However, the plasticity of these larger PDPs and their ability to change structure under different conditions make them appealing peptide drug scaffolds.
The iron maiden. Cytosolic aconitase/IRP1 conformational transition in the regulation of ferritin translation and iron hemostasis
Authors: Hognon Cécilia , Bignon Emmanuelle , Harle Guillaume , Touche Nadège , Grandemange Stéphanie , Monari Antonio 
Published: July 2021

AbstractMaintaining iron homeostasis is fundamental for almost all living being, and its deregulation correlates with severe and debilitating pathologies. The process is made more complicated by the omnipresence of iron and by its role as a fundamental component of a number of crucial metallo proteins. The response to modifications in the amount of the free iron pool is performed via the inhibition of ferritin translation by sequestering consensus messenger RNA (mRNA) sequences. In turn this is regulated by the iron-sensitive conformational equilibrium between aconitase and IRP, mediated by the presence of an iron-sulfur cluster. In this contribution we analyze by full-atom molecular dynamics simulation, the factors leading to both the interaction with mRNA, and the conformational transition. Furthermore, the role of the iron-sulfur cluster in driving the conformational transition is assessed by obtaining the related free energy profile via enhanced sampling molecular dynamics simulations.
The contribution of uncharted RNA sequences to tumor identity in lung adenocarcinoma
Authors: Wang Yunfeng , Xue Haoliang , Aglave Marine , Lainé Antoine , Gallopin Mélina , Gautheret Daniel 
Published: July 2021

AbstractBackgroundTranscriptome analysis of cancer tissues has been instrumental in defining tumor subtypes, diagnostic signatures and cancer regulatory networks. Cancer transcriptomes are still predominantly analyzed at the level of gene expression. Few studies have addressed transcript-level variations, and most of these only looked at splice variants. Previously we introduced a k-mer based, reference-free method, DE-kupl, that performs differential analysis of RNA-seq data at the k-mer level, which enables distinguishing RNAs differing by a single nucleotide. Here we evaluate the significance of differential events discovered by this method in two independent lung adenocarcinoma RNA-seq datasets (N=583 and N=154).ResultsFocusing on differential events in a tumor vs normal setting, we found events in endogenous repeats, alternative splicing and polyadenylation sites, long non-coding RNAs, retained introns and unmapped RNAs. Replicability was highly significant for most event classes (assessed by comparing to events shared between unrelated tumors). Overall about 160,000 differential k-mer contigs were shared between datasets, including a large set of sequences from hypervariable genes such as immunoglobulins,SFTPand mucin genes. Most interestingly, we identified a set of novel tumor-specific long non-coding RNAs in intergenic and intronic regions. We found that expressed endogenous transposons defined two major groups of patients (high/low repeat expression) with distinct clinical characteristic. A number of repeats, intronic RNAs and lincRNA achieved strong patient stratification in univariate or multivariate survival models. Finally, using antigen presentation prediction, we identified 55 contigs predicted to produce recurrent tumor-specific antigens.ConclusionsK-mer based RNA-seq analysis enables description of cancer transcriptomes at nucleotide precision, independently of prior transcript annotation. Application to lung cancer data uncovered events stemming from a wide variety of transcriptional and postranscriptional mechanisms. Among those events, a significant subset was replicable between cohorts, thus constituting novel RNA hallmarks of cancer. The code is available at:https://github.com/Transipedia/dekupl-lung-cancer-inter-cohort.
Structural and functional network-level reorganization in the coding of auditory motion directions and sound source locations in the absence of vision
Authors: Battal Ceren , Gurtubay-Antolin Ane , Rezk Mohamed , Mattioni Stefania , Bertonati Giorgia , Occelli Valeria , Bottini Roberto , Targher Stefano , Maffei Chiara , Jovicich Jorge , Collignon Olivier 
Published: July 2021

AbstracthMT+/V5 is a region in the middle occipito-temporal cortex that responds preferentially to visual motion in sighted people. In case of early visual deprivation, hMT+/V5 enhances its response to moving sounds. Whether hMT+/V5 contains information about motion directions and whether the functional enhancement observed in the blind is motion specific, or also involves sound source location, remains unsolved. Moreover, the impact of this crossmodal reorganization of hMT+/V5 on the regions typically supporting auditory motion processing, like the human Planum Temporale (hPT), remains equivocal. We used a combined functional and diffusion MRI approach and individual in-ear recordings to study the impact of early blindness on the brain networks supporting spatial hearing, in male and female humans. Whole-brain univariate analysis revealed that the anterior portion of hMT+/V5 responded to moving sounds in sighted and blind people, while the posterior portion was selective to moving sounds only in blind participants. Multivariate decoding analysis revealed that the presence of motion directions and sound positions information was higher in hMT+/V5 and lower in hPT in the blind group. While both groups showed axis-of-motion organization in hMT+/V5 and hPT, this organization was reduced in the hPT of blind people. Diffusion MRI revealed that the strength of hMT+/V5 – hPT connectivity did not differ between groups, whereas the microstructure of the connections was altered by blindness. Our results suggest that the axis-of-motion organization of hMT+/V5 does not depend on visual experience, but that blindness alters the response properties of occipito-temporal networks supporting spatial hearing in the sighted.Significance StatementSpatial hearing helps living organisms navigate their environment. This is certainly even more true in people born blind. How does blindness affect the brain network supporting auditory motion and sound source location? Our results show that the presence of motion directions and sound positions information was higher in hMT+/V5 and lower in hPT in blind relative to sighted people; and that this functional reorganization is accompanied by microstructural (but not macrostructural) alterations in their connections. These findings suggest that blindness alters crossmodal responses between connected areas that share the same computational goals.
Large-scale genome-wide association study of food liking reveals genetic determinants and genetic correlations with distinct neurophysiological traits
Authors: May-Wilson Sebastian , Matoba Nana , Wade Kaitlin , Hottenga Jouke-Jan , Concas Maria Pina , Mangino Massimo , Grzeszkowiak Eryk J. , Menni Cristina , Gasparini Paolo , Timpson Nicholas J. , Veldhuizen Maria G. , de Geus Eco , Wilson James F. , Pirastu Nicola 
Published: July 2021

AbstractVariable preferences for different foods are among the main determinants of their intake and are influenced by many factors, including genetics. Despite considerable twins’ heritability, studies aimed at uncovering food-liking genetics have focused mostly on taste receptors. Here, we present the first results of a large-scale genome-wide association study of food liking conducted on 161,625 participants from UK Biobank. Liking was assessed over 139 specific foods using a 9-point hedonic scale. After performing GWAS, we used genetic correlations coupled with structural equation modelling to create a multi-level hierarchical map of food liking. We identified three main dimensions: high caloric foods defined as “Highly palatable”, strong-tasting foods ranging from alcohol to pungent vegetables, defined as “Learned” and finally “Low caloric” foods such as fruit and vegetables. The “Highly palatable” dimension was genetically uncorrelated from the other two, suggesting that two independent processes underlie liking high reward foods and the Learned/Low caloric ones. Genetic correlation analysis with the corresponding food consumption traits revealed a high correlation, while liking showed twice the heritability compared to consumption. For example, fresh fruit liking and consumption showed a genetic correlation of 0.7 with heritabilities of 0.1 and 0.05, respectively. GWAS analysis identified 1401 significant food-liking associations located in 173 genomic loci, with only 11 near taste or olfactory receptors. Genetic correlation with morphological and functional brain data (33,224 UKB participants) uncovers associations of the three food-liking dimensions with non-overlapping, distinct brain areas and networks, suggestive of separate neural mechanisms underlying the liking dimensions. In conclusion, we created a comprehensive and data-driven map of the genetic determinants and associated neurophysiological factors of food liking beyond taste receptor genes.
Rapid redistribution and extensive binding of NANOG and GATA6 at shared regulatory elements underlie specification of divergent cell fates
Authors: Thompson Joyce J. , Lee Daniel J. , Mitra Apratim , Frail Sarah , Dale Ryan , Rocha Pedro P. 
Published: July 2021

ABSTRACTEstablishment of divergent cell types from a common progenitor requires transcription factors (TFs) to promote lineage-restricted transcriptional programs while suppressing alternative fates. In the mouse blastocyst, cells of the inner cell mass (ICM) coexpress NANOG and GATA6, two TFs that drive the bifurcation of these progenitors into either the epiblast (Epi) or the primitive endoderm (PrE), respectively. Here, using in vitro differentiation, we describe the molecular mechanisms of how GATA6 quickly induces the PrE fate while repressing the Epi lineage. GATA6 functions as a pioneer TF by inducing nucleosome repositioning at regulatory elements controlling PrE genes, making them accessible for deposition of active histone marks and leading to rewiring of chromatin interactions and ultimately transcriptional activation. GATA6 also binds most regulatory elements of Epi genes followed by eviction of the Epispecific TFs NANOG and SOX2, loss of active histone marks, and reduction in chromatin accessibility that culminates in transcriptional repression. Unexpectedly, evicted NANOG and SOX2 transiently bind PrE regulatory elements occupied by GATA6. Our study shows that GATA6 binds and modulate the same regulatory elements as Epi TFs, a phenomenon we also validated in blastocysts. We propose that the ability of PrE and Epi-specific TFs to extensively bind and regulate the same gene networks contributes to ICM plasticity and allows rapid cell lineage specification by coordinating both activation and repression of divergent transcriptional programs.
Evolution of Regulatory Complexity for Cell-Cycle Control
Authors: von der Dunk Samuel H. A. , Snel Berend , Hogeweg Paulien 
Published: July 2021

AbstractHow complexity arises is a fundamental evolutionary question. Complex gene regulation is thought to arise by the interplay between adaptive and non-adaptive forces at multiple organizational levels. Using a computational model, we investigate how complexity arises in cell-cycle regulation. Starting from the well-known Caulobacter crescentus network, we study how cells adapt their cell-cycle behaviour to a gradient of limited nutrient conditions using 10 replicate in silico evolution experiments.We find adaptive expansion of the gene regulatory network: improvement of cell-cycle behaviour allows cells to overcome the inherent cost of complexity. Replicates traverse different evolutionary trajectories leading to distinct eco-evolutionary strategies. In four replicates, cells evolve a generalist strategy to cope with a variety of nutrient levels; in two replicates, different specialist cells evolve for specific nutrient levels; in the remaining four replicates, an intermediate strategy evolves. The generalist and specialist strategies are contingent on the regulatory mechanisms that arise early in evolution, but they are not directly linked to network expansion and overall fitness.This study shows that functionality of cells depends on the combination of gene regulatory network topology and genome structure. For example, the positions of dosage-sensitive genes are exploited to signal to the regulatory network when replication is completed, forming a de novo evolved cell-cycle checkpoint. Complex gene regulation can arise adaptively both from expansion of the regulatory network and from the genomic organization of the elements in this network, demonstrating that to understand complex gene regulation and its evolution, it is necessary to integrate systems that are often studied separately.
Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex
Authors: Bercum Florencia M , Navarro Gomez Maria J , Saddoris Michael P 
Published: July 2021

AbstractStress experienced early in development can have profound influences on developmental trajectories and ultimately behaviors in adulthood. Potent stressors during brain maturation can profoundly disrupt prefrontal cortical areas in particular, which can set the stage for prefrontal-dependent alterations in fear regulation and risk of drug abuse in adulthood. Despite these observations, few studies have investigated in vivo signaling in prefrontal signals in animals with a history of early life stress (ELS). Here, rats with ELS experienced during the first post-natal week were then tested on a conditioned suppression paradigm during adulthood. During conditioned suppression, electrophysiological recordings were made in the ventral medial prefrontal cortex (vmPFC) during presentations of a fear-associated cues that resolved both single-unit activity and local field potentials (LFPs). Relative to unstressed controls, ELS-experienced rats showed greater fear-related suppression of lever pressing. During presentations of the fear-associated cue (CS+), neurons in the vmPFC of ELS animals showed a significant increase in the probability of excitatory encoding relative to controls, and excitatory phasic responses in the ELS animals were reliably of higher magnitude than Controls. In contrast, vmPFC neurons in ELS subjects better discriminated between the shock-associated CS+ and the neutral (“safe”) CS-cue than Controls. LFPs recorded in the same locations revealed that high gamma band (65-95 Hz) oscillations were strongly potentiated in Controls during presentation of the fear-associated CS+ cue, but this potentiation was abolished in ELS subjects. Notably, no other LFP spectra differed between ELS and Controls for either the CS+ or CS-. Collectively, these data suggest that ELS experience alters the neurobehavioral functions of PFC in adulthood that are critical for processing fear regulation. As such, these alterations may also provide insight into to increased susceptibility to other PFC-dependent processes such as risk-based choice, motivation, and regulation of drug use and relapse in ELS populations.