bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situstructure of rotavirus VP1 RNA-dependent RNA polymerase
Authors: Jenni Simon , Salgado Eric N. , Herrmann Tobias , Li Zongli , Grant Timothy , Grigorieff Nikolaus , Trapani Stefano , Estrozi Leandro F. , Harrison Stephen C. 
Published: April 2019

AbstractRotaviruses, like other non-enveloped, double-strand RNA (dsRNA) viruses, package an RNA-dependent RNA polymerase (RdRp) with each duplex of their segmented genomes. Rotavirus cell entry results in loss of an outer protein layer and delivery into the cytosol of an intact, inner capsid particle (the “double-layer particle” or DLP). The RdRp, designated VP1, is active inside the DLP; each VP1 achieves many rounds of mRNA transcription from its associated genome segment. Previous work has shown that one VP1 molecule lies close to each fivefold axis of the icosahedrally symmetric DLP, just beneath the inner surface of its protein shell, embedded in tightly packed RNA. We have determined a high-resolution structure for the rotavirus VP1 RdRpin situ, by local reconstruction of density around individual fivefold positions. We have analyzed intact virions (“triple-layer particles” or TLPs), non-transcribing DLPs and transcribing DLPs. Outer layer dissociation enables the DLP to synthesize RNA,in vitroas well asin vivo, but appears not to induce any detectable structural change in the RdRp. Addition of NTPs, Mg2+, and S-adenosyl methionine, which allows active transcription, results in conformational rearrangements, in both VP1 and the DLP capsid shell protein, that allow a transcript to exit the polymerase and the particle. The position of VP1 (among the five symmetrically related alternatives) at one vertex does not correlate with its position at other vertices. This stochastic distribution of site occupancies limits long-range order in the 11-segment, dsRNA genome.
Deleterious Mutation Accumulation and the Long-Term Fate of Chromosomal Inversions
Authors: Berdan Emma L. , Blanckaert Alexandre , Butlin Roger K. , Bank Claudia 
Published: April 2019

AbstractChromosomal inversions contribute widely to adaptation and speciation, yet they present a unique evolutionary puzzle as both their allelic content and frequency evolve in a feedback loop. In this simulation study, we quantified the role of the allelic content in determining the long-term fate of the inversion. Recessive deleterious mutations accumulated on both arrangements with most of them being private to a given arrangement. This led to increasing overdominance, allowing for the maintenance of the inversion polymorphism and generating strong non-adaptive divergence between arrangements. The accumulation of mutations was mitigated by gene conversion but nevertheless led to the fitness decline of at least one homokaryotype under all considered conditions. Surprisingly, this fitness degradation could be permanently halted by the branching of an arrangement into multiple highly divergent haplotypes. Our results highlight the dynamic features of inversions by showing how the non-adaptive evolution of allelic content can play a major role in the fate of the inversion.Author SummaryA chromosomal inversion is a segment of the chromosome that is flipped (inverted arrangement) relative to the normal orientation (standard arrangement). Such structural mutations may facilitate evolutionary processes such as adaptation and speciation, because reduced recombination in inverted regions allows beneficial combinations of alleles to behave as a “single unit”. This locally reduced recombination can have major consequences for the evolution of the allelic content inside the inversion. We used simulations to investigate some of these consequences. Inverted regions tended to accumulate more deleterious recessive mutations than the rest of the genome, which decreased the fitness of homokarotypes (individuals with two copies of the same arrangement). This led to a strong selective advantage for heterokaryotypes (individuals with one copy of each arrangement), maintaining the inversion polymorphism in the population. The accumulation of deleterious mutations also resulted in strong divergence between arrangements. We occasionally observed an arrangement that diverged into a small number of highly differentiated haplotypes, stopping the fitness decrease in homokaryotypes. Our results highlight the dynamic features of inversions by showing how the evolution of allelic content can greatly affect the fate of an inversion.
Inflammasome-independent role for NLRP3 in controlling innate anti-helminth immunity and tissue repair in the lung
Authors: Chenery AL , Alhallaf R , Agha Z , Ajendra J , Parkinson JE , Cooper MM , Chan BHK , Eichenberger RM , Dent LA , Robertson AAB , Kupz A , Brough D , Loukas A , Sutherland TE , Allen JE , Giacomin PR 
Published: April 2019

AbstractAlternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R-dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis suggesting a potential role for the inflammasome in the IL-1-mediated innate response to infection. While inflammasome proteins such as NLRP3 have important pro-inflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3−/− mice with N. brasiliensis. Unexpectedly, compared to WT mice, infected Nlrp3−/− mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3−/− mice exhibited elevated type 2 gene expression compared to WT mice. Notably, inflammasome activation was not evident early post-infection with N. brasiliensis and in contrast to Nlrp3−/− mice, anti-helminth responses were unaffected in caspase-1/11 deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 can constrain lung neutrophilia and helminth killing and negatively regulate type 2 immune responses in an inflammasome-independent manner.
Generation of viral vectors specific to neuronal subtypes of targeted brain regions by Enhancer-Driven Gene Expression (EDGE)
Authors: Nair Rajeevkumar Raveendran , Blankvoort Stefan , Lagartos Maria Jose , Kentros Cliff 
Published: April 2019

SummaryUnderstanding brain function requires understanding neural circuits at the level of specificity at which they operate. While recent years have seen the development of a variety of remarkable molecular tools for the study of neural circuits, their utility is currently limited by the inability to deploy them in specific elements of native neural circuits, i.e. particular neuronal subtypes. One can obtain a degree of specificity with neuron-specific promoters, but native promoters are almost never sufficiently specific restricting this approach to transgenic animals. We recently showed that one can obtain transgenic mice with augmented anatomical specificity in targeted brain regions by identifyingcis-regulatory elements (i.e. enhancers) uniquely active in those brain regions and combining them with a heterologous promoter, an approach we call EDGE (Enhancer-Driven Gene Expression). Here we extend this strategy to the generation of viral (rAAV) vectors, showing that when combined with the right minimal promoter they largely recapitulate the specificity seen in the corresponding transgenic lines in wildtype animals, even of another species. Because active enhancers can be identified in any tissue sample, this approach promises to enable the kind of circuit-specific manipulations in any species. This should not only greatly enhance our understanding of brain function, but may one day even provide novel therapeutic avenues to correct the imbalances in neural circuits underlying many disorders of the brain.
The Role of the Subthalamic Nucleus in Inhibitory Control of Oculomotor Behavior in Parkinson’s Disease
Authors: Bakhtiari Shahab , Altinkaya Ayca , Pack Christopher C. , Sadikot Abbas F. 
Published: April 2019

AbstractThe ability to inhibit an inappropriate action in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple experimental task within the oculomotor repertoire that can be used to test this ability. The task involves an inhibition of a saccade to the peripheral target (pro-saccade) and generation of a voluntary eye movement toward the mirror position (anti-saccade). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior. However, the precise role of different components in generation of anti-saccade behavior is still uncertain. Parkinson’s disease patients with implanted deep brain stimulation (DBS) in subthalamic nucleus (STN) provide us with a unique opportunity to investigate the role of STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinson’s disease patients on anti- and pro-saccade tasks ON and OFF STN DBS and ON and OFF dopaminergic medication. We made three main observations. First, STN DBS increases the anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, there is an interaction between dopamine replacement therapy and STN DBS. More specifically, L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS can induce different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.
Rhythms of Transcription in Field-Grown Sugarcane Are Highly Organ Specific
Authors: de Barros Dantas Luíza Lane , Almeida-Jesus Felipe Marcelo , de Lima Natalia Oliveira , Alves-Lima Cícero , Nishiyama Milton Yutaka , Carneiro Monalisa Sampaio , Souza Glaucia Mendes , Hotta Carlos Takeshi 
Published: April 2019

AbstractWe investigated whether different specialized organs in field-grown sugarcane follow the same temporal rhythms in transcription. We assayed the transcriptomes of three organs during the day: leaf, a source organ; internodes 1 and 2, sink organs focused on cell division and elongation; and internode 5, a sink organ focused on sucrose storage. The leaf had twice as many rhythmic transcripts (>68%) as internodes, and the rhythmic transcriptomes of the two internodes were more similar to each other than to those of the leaves. More transcripts were rhythmic under field conditions than under circadian conditions and most of their peaks were during the day. Among the transcripts that were considered expressed in all three organs, only 7.4% showed the same rhythmic time course pattern. The central oscillators of these three organs — the networks that generate circadian rhythms — had similar dynamics with different amplitudes. The differences between the rhythmic transcriptomes in circadian conditions and field conditions highlight the importance of field experiments to understand the plant circadian clock in natura. The highly specialized nature of the rhythmic transcriptomes in sugarcane organs probably arises from amplitude differences in tissue-specific circadian clocks and different sensitivities to environmental cues.One sentence summaryThe rhythmic transcriptome of field-grown sugarcane is highly organ-specific.
Aging induces Nlrp3 inflammasome dependent adipose B cell expansion to impair metabolic homeostasis
Authors: Camell Christina D. , Lee Aileen , Günther Patrick , Goldberg Emily L. , Spadaro Olga , Youm Yun-Hee , Bartke Andrzej , Hubbard Gene B. , Ikeno Yuji , Ruddle Nancy H. , Schultze Joachim , Dixit Vishwa Deep 
Published: April 2019

SummaryVisceral adiposity in elderly is associated with alterations in adipose tissue immune cells leading to inflammation and metabolic dysfunction. The Nlrp3 inflammasome is a critical regulator of macrophage activation, inflammation, and immunometabolism in visceral adipose tissue during aging; however, the potential contribution of adipose tissue B cells is unexplored. Here, we show that aging expands adipose-resident B cells and fat-associated lymphoid clusters (FALCs) in visceral white adipose tissue. Adipose tissue B cells exhibit a memory-like B cell profile similar to the phenotype of aged B cells that are increased in spleen of old mice. Mechanistically, the age-induced FALC formation and adipose B cell expansion, but not B cell transcriptional program, is dependent on the Nlrp3 inflammasome. Furthermore, B cell depletion in aged mice restores lipolysis and defense against loss of core body temperature during cold stress. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging adipose tissue.Highlights- Adipose-resident aged B cells are increased in fat-associated lymphoid clusters (FALC)- FALC formation and adipose-resident B cell expansion during aging are regulated by the Nlrp3 inflammasome- Nlrp3 and B cell depletion in aging restores lipolysis and improves cold tolerancea
An analytical theory of balanced cellular growth
Authors: Dourado Hugo , Lercher Martin J. 
Published: April 2019

ABSTRACTThe biological fitness of unicellular organisms is largely determined by their balanced growth rate, i.e., by the rate with which they replicate their biomass composition. Natural selection on this growth rate occurred under a set of physicochemical constraints, including mass conservation, reaction kinetics, and limits on dry mass per volume; mathematical models that maximize the balanced growth rate while accounting explicitly for these constraints are inevitably nonlinear and have been restricted to small, non-realistic systems. Here, we lay down a general theory of balanced growth states, providing explicit expressions for protein concentrations, fluxes, and the growth rate. These variables are functions of the concentrations of cellular components, for which we calculate marginal fitness costs and benefits that can be related to metabolic control coefficients. At maximal growth rate, the net benefits of all concentrations are equal. Based solely on physicochemical constraints, the growth balance analysis (GBA) framework introduced here unveils fundamental quantitative principles of cellular growth and leads to experimentally testable predictions.
Mapping-based Genome Size Estimation
Authors: Natarajan Shakunthala , Gehrke Jessica , Pucker Boas 
Published: April 2019

AbstractWhile the size of chromosomes can be measured under a microscope, obtaining the exact size of a genome remains a challenge. Biochemical methods and k-mer distribution-based approaches allow only estimations. An alternative approach to estimate the genome size based on high contiguity assemblies and read mappings is presented here. Analyses ofArabidopsis thalianaandBeta vulgarisdata sets are presented to show the impact of different parameters.Oryza sativa, Brachypodium distachyon,Solanum lycopersicum,Vitis vinifera, andZea mayswere also analyzed to demonstrate the broad applicability of this approach. Mapping-based Genome Size Estimation (MGSE) and additional scripts are available on GitHub:https://github.com/bpucker/MGSE.
Motto: Representing motifs in consensus sequences with minimum information loss
Authors: Wang Mengchi , Wang David , Zhang Kai , Ngo Vu , Fan Shicai , Wang Wei 
Published: April 2019

ABSTRACTSequence analysis frequently requires intuitive understanding and convenient representation of motifs. Typically, motifs are represented as position weight matrices (PWMs) and visualized using sequence logos. However, in many scenarios, representing motifs by wildcard-style consensus sequences is compact and sufficient for interpreting the motif information and search for motif match. Based on mutual information theory and Jenson-Shannon Divergence, we propose a mathematical framework to minimize the information loss in converting PWMs to consensus sequences. We name this representation as sequence Motto and have implemented an efficient algorithm with flexible options for converting motif PWMs into Motto from nucleotides, amino acids, and customized alphabets. Here we show that this representation provides a simple and efficient way to identify the binding sites of 1156 common TFs in the human genome. The effectiveness of the method was benchmarked by comparing sequence matches found by Motto with PWM scanning results found by FIMO. On average, our method achieves 0.81 area under the precision-recall curve, significantly (p-value < 0.01) outperforming all existing methods, including maximal positional weight, Douglas and minimal mean square error. We believe this representation provides a distilled summary of a motif, as well as the statistical justification.AVAILABILITYMotto is freely available at http://wanglab.ucsd.edu/star/motto.
Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2
Authors: Cernilogar Filippo M. , Hasenöder Stefan , Wang Zeyang , Scheibner Katharina , Burtscher Ingo , Sterr Michael , Smialowski Pawel , Groh Sophia , Evenroed Ida M. , Gilfillan Gregor D. , Lickert Heiko , Schotta Gunnar 
Published: April 2019

AbstractPioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they can initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.
Individual differences in the influence of mental imagery on conscious perception
Authors: Dijkstra N. , Hinne M. , Bosch S.E. , van Gerven M.A.J. 
Published: April 2019

AbstractMental imagery and visual perception rely on similar neural mechanisms, but the function of this overlap remains unclear. One idea is that imagery can influence perception. Previous research has shown that imagining a stimulus prior to binocular presentation of rivalling stimuli increases the chance of perceiving the imagined stimulus. In this study we investigated how this effect interacts with bottom-up sensory input by comparing psychometric response curves for congruent and incongruent imagery in humans. A Bayesian hierarchical model was used, allowing us to simultaneously study group-level effects as well as effects for individual participants. We found strong effects of both imagery as well as its interaction with sensory evidence within individual participants. However, the direction of these effects were highly variable between individuals, leading to weak effects at the group level. This highlights the heterogeneity of conscious perception and emphasizes the need for individualized investigation of such complex cognitive processes.
Phylogenetic and Spatial Distribution of Evolutionary Isolation and Threat in Turtles and Crocodilians (Non-Avian Archosauromorphs)
Authors: Colston Timothy J. , Kulkarni Pallavi , Jetz Walter , Pyron R. Alexander 
Published: April 2019

AbstractThe origin of turtles and crocodiles and their easily recognized body forms dates to the Triassic. Despite their long-term success, extant species diversity is low, and endangerment is extremely high compared to other terrestrial vertebrate groups, with ~ 65% of ~25 crocodilian and ~360 turtle species now threatened by exploitation and habitat loss. Here, we combine available molecular and morphological evidence with machine learning algorithms to present a phylogenetically-informed, comprehensive assessment of diversification, threat status, and evolutionary distinctiveness of all extant species. In contrast to other terrestrial vertebrates and their own diversity in the fossil record, extant turtles and crocodilians have not experienced any mass extinctions or shifts in diversification rate, or any significant jumps in rates of body-size evolution over time. We predict threat for 114 as-yet unassessed or data-deficient species and identify a concentration of threatened crocodile and turtle species in South and Southeast Asia, western Africa, and the eastern Amazon. We find that unlike other terrestrial vertebrate groups, extinction risk increases with evolutionary distinctiveness: a disproportionate amount of phylogenetic diversity is concentrated in evolutionarily isolated, at-risk taxa, particularly those with small geographic ranges. Our findings highlight the important role of geographic determinants of extinction risk, particularly those resulting from anthropogenic habitat-disturbance, which affect species across body sizes and ecologies.
MerMAIDs: A novel family of metagenomically discovered, marine, anion-conducting and intensely desensitizing channelrhodopsins
Authors: Oppermann Johannes , Fischer Paul , Silapetere Arita , Liepe Bernhard , Rodriguez-Rozada Silvia , Flores-Uribe José , Peter Enrico , Keidel Anke , Vierock Johannes , Kaufmann Joel , Broser Matthias , Luck Meike , Bartl Franz , Hildebrandt Peter , Wiegert J. Simon , Béjà Oded , Hegemann Peter , Wietek Jonas 
Published: April 2019

AbstractChannelrhodopsins (ChRs) are algal light-gated ion channels widely used as optogenetic tools for manipulating neuronal activity. ChRs desensitize under continuous bright-light illumination, resulting in a significant decline of photocurrents. We describe a novel, metagenomically identified family of phylogenetically distinct anion-conducting ChRs (designated MerMAIDs). MerMAIDs almost completely desensitize during continuous illumination due to accumulation of a late non-conducting photointermediate that disrupts the ion permeation pathway. MerMAID desensitization can be fully explained by a single photocycle in which a long-lived desensitized state follows the short-lived conducting state. A conserved cysteine is the critical factor in desensitization, as its mutation results in recovery of large stationary photocurrents. The rapid desensitization of MerMAIDs enables their use as optogenetic silencers for transient suppression of individual action potentials without affecting subsequent spiking during continuous illumination. Our results could facilitate the development of further novel optogenetic tools from metagenomic databases and enhance general understanding of ChR function.