bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining chromatin state transitions predicts a network that modulates cell wall remodeling in phosphate-starved rice shoots
Authors: Foroozani Maryam , Zahraeifard Sara , Oh Dong-Ha , Wang Guannan , Dassanayake Maheshi , Smith Aaron 
Published: July 2019

AbstractPhosphorus (P) is an essential plant macronutrient vital to fundamental metabolic processes. Plant-available P is low in most soils, making it a frequent limiter of growth. Declining P reserves for fertilizer production exasperates this agricultural challenge. Plants modulate complex responses to fluctuating P levels via global transcriptional regulatory networks. Although chromatin structure plays a substantial role in controlling gene expression, the chromatin dynamics involved in regulating P homeostasis have not been determined. Here we define distinct chromatin states across the rice genome by integrating multiple aspects of chromatin structure, including the H2A.Z histone variant, H3K4me3 modification, and nucleosome positioning. In response to P starvation, 40% of all protein-coding genes exhibit a transition from one chromatin state to another at their transcription start site. Several of these transitions are enriched in subsets of genes differentially expressed by P deficiency. The most prominent subset supports the presence of a coordinated signaling network that targets cell wall structure and is regulated in part via a decrease of H3K4me3 at the transcription start site. The P-starvation induced chromatin dynamics and correlated genes identified here will aid in enhancing P-use efficiency in crop plants, benefitting global agriculture.One sentence summaryCombining data for three components of chromatin structure from control and phosphate-starved rice shoots reveals specific chromatin state transitions that correlate with subsets of functionally distinct differentially-expressed genes.
Functional community assembly and turnover along elevation and latitude
Authors: Jarzyna Marta A. , Quintero Ignacio , Jetz Walter 
Published: July 2019

AbstractThe drivers of community coexistence are known to vary with environment, but their consistency across latitudes and scales, and resulting conservation implications, remain little understood. Here, we combine functional and phylogenetic evidence along elevations to document strong biotic constraints on coexistence in avian communities in both benign (tropical low elevations) and severely harsh (temperate/polar highlands) environments. Assemblages in both are marked by high assemblage functional uniqueness, whereas in tropical highlands and temperate/polar low elevations there is strong functionally redundancy and pronounced environmental constraints. Only in harsh environments is phylogeny an effective surrogate for functional assemblage structure, reflecting nuanced shifts in the position, shape, and composition of measured multivariate trait space along gradients. Independent of scale and latitude, high elevation assemblages emerge as exceptionally susceptible to functional change.
Early diverging fungus Mucor circinelloides lacks centromeric histone CENP-A and displays a mosaic of point and regional centromeres
Authors: Navarro-Mendoza María Isabel , Pérez-Arques Carlos , Panchal Shweta , Nicolás Francisco E. , Mondo Stephen J. , Ganguly Promit , Pangilinan Jasmyn , Grigoriev Igor V. , Heitman Joseph , Sanyal Kaustuv , Garre Victoriano 
Published: July 2019

AbstractCentromeres are rapidly evolving across eukaryotes, despite performing a conserved function to ensure high fidelity chromosome segregation. CENP-A chromatin is a hallmark of a functional centromere in most organisms. Due to its critical role in kinetochore architecture, the loss of CENP-A is tolerated in only a few organisms, many of which possess holocentric chromosomes. Here, we characterize the consequence of the loss of CENP-A in the fungal kingdom. Mucor circinelloides, an opportunistic human pathogen, lacks CENP-A along with the evolutionarily conserved CENP-C, but assembles a monocentric chromosome with a localized kinetochore complex throughout the cell cycle. Mis12 and Dsn1, two conserved kinetochore proteins were found to bind nine short overlapping regions, each comprising an ∼200-bp AT-rich sequence followed by a centromere-specific conserved motif that echoes the structure of budding yeast point centromeres. Resembling fungal regional centromeres, these core centromere regions are embedded in large genomic expanses devoid of genes yet marked by Grem-LINE1s, a novel retrotransposable element silenced by the Dicer-dependent RNAi pathway. Our results suggest that these hybrid features of point and regional centromeres arose from the absence of CENP-A, thus defining novel mosaic centromeres in this early-diverging fungus.
A selective and rapid cell-permeable inhibitor of human caspase-3
Authors: Solania Angelo , González-Páez Gonzalo E. , Wolan Dennis W. 
Published: July 2019

ABSTRACTThe individual roles and overlapping functionalities the twelve human caspases have during apoptosis and other cellular processes remain poorly resolved primarily due to a lack of chemical tools. Here we present a new selective caspase-3 inhibitor, termed Ac-ATS010-KE, with rapid and irreversible binding kinetics. Relative to previously designed caspase-3-selective molecules that have tremendously abated inhibitory rates and thus limited use in biological settings, the improved kinetics of Ac-ATS010-KE permit its use in a cell-based capacity. We demonstrate that Ac-ATS010-KE prevents apoptosis with comparable efficacy to the general caspase inhibitor Ac-DEVD-KE and surprisingly does so without side-chain methylation. This observation is in contrast to the well-established peptide modification strategy typically employed for improving cellular permeability. Ac-ATS010-KE protects against extrinsic apoptosis, which demonstrates the utility of a thiophene carboxylate leaving group in biological settings, challenges the requisite neutralization of free carboxylic acids to improve cell permeability, and provides a tool-like compound to interrogate the role of caspase-3 in a variety of cellular processes.
Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability
Authors: Wang Richard J. , Thomas Gregg W.C. , Raveendran Muthuswamy , Harris R. Alan , Doddapaneni Harshavardhan , Muzny Donna M. , Capitanio John P. , Radivojac Predrag , Rogers Jeffrey , Hahn Matthew W. 
Published: July 2019

AbstractMutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accurate comparisons of whole-genome sequences between parents and offspring. Studies in humans have revealed that the paternal age at conception explains most of the variation in mutation rate: each additional year of paternal age in humans leads to approximately 1.5 additional mutations inherited by the child. Here, we present an estimate of the de novo mutation rate in the rhesus macaque (Macaca mulatta) using whole-genome sequence data from 32 individuals in four large pedigrees. We estimated an average mutation rate of 0.58 × 10-8 per base pair per generation (at an average parental age of 7.5 years), much lower than found in direct estimates from great apes (including human, chimpanzee, and gorilla). As in humans, older macaque fathers transmit more mutations to their offspring, approximately 1.5 extra mutations per year in our probands. Mutations at CpG sites accounted for 24% of all observed point mutations. We found that the rate of mutation accumulation after puberty is similar between macaques and humans, but that a smaller number of mutations accumulate before puberty in macaques. We additionally investigated the role of paternal age on offspring sociability, a proxy for normal neurodevelopment. In 203 male macaques studied in large social groups, we found no relationship between paternal age and multiple measures of social function. Our findings are consistent with the hypothesis that the increased risk of neurodevelopmental disorders with paternal age in primates is not primarily due to de novo mutations.
Fighting or Embracing Multiplicity in Neuroimaging? Neighborhood Leverage versus Global Calibration
Authors: Chen Gang , Taylor Paul A. , Cox Robert W. , Pessoa Luiz 
Published: July 2019

AbstractNeuroimaging faces the daunting challenge of multiple testing – an instance ofmultiplicity– that is associated with two other issues to some extent: low inference efficiency and poor reproducibility. Typically, the same statistical model is applied to each spatial unit independently in the approach of massively univariate modeling. In dealing with multiplicity, the general strategy employed in the field is the same regardless of the specifics: trust the local “unbiased” effect estimates while adjusting the extent of statistical evidence at the global level. However, in this approach, modeling efficiency is compromised because each spatial unit (e.g., voxel, region, matrix element) is treated as an isolated and independent entity during massively univariate modeling. In addition, the required step of multiple testing “correction” by taking into consideration spatial relatedness, orneighborhood leverage, can only partly recoup statistical efficiency, resulting in potentially excessive penalization as well as arbitrariness due to thresholding procedures. Moreover, the assigned statistical evidence at the global level heavily relies on the data space (whole brain or a small volume). The present paper reviews how Stein’s paradox (1956) motivates a Bayesian multilevel (BML) approach that, rather than fighting multiplicity, embraces it to our advantage through aglobal calibrationprocess among spatial units. Global calibration is accomplished via a Gaussian distribution for the cross-region effects whose properties are not a priori specified, but a posteriori determined by the data at hand through the BML model. Our framework therefore incorporates multiplicity as integral to the modeling structure, not a separate correction step. By turning multiplicity into a strength, we aim to achieve five goals: 1) improve model efficiency with higher predictive accuracy, 2) control the errors of incorrect magnitude and incorrect sign, 3) validate each model relative to competing candidates, 4) reduce the reliance and sensitivity on the choice of data space, and 5) encourage full results reporting. Our modeling proposal reverberates with recent proposals to eliminate the dichotomization of statistical evidence (“significant” vs. “non-significant”), to improve the interpretability of study findings, as well as to promote reporting the full gamut of results (not only “significant” ones), thereby enhancing research transparency and reproducibility.
Primitive and modern swimmers solve the challenges of turning similarly to achieve high maneuverability
Authors: Dabiri J. O. , Colin S. P. , Gemmell B. J. , Lucas K. N. , Leftwich Megan C. , Costello John H. 
Published: July 2019

AbstractAnimal swimmers alter trajectories – or turn - for a variety of critical life functions such as feeding, mating and avoiding predation. Yet turning represents a fundamental dilemma based in rotational dynamics: the torque powering a turn is favored by an expanded body configuration, yet minimizing the resistance to a turn (the moment of inertia) is favored by a contracted body configuration. How do animals balance these opposing demands to achieve high maneuverability? By noninvasively measuring fluid and body motions, we found that both jellyfish (Aurelia aurita) and fish (Danio rerio) initially maximized torque using previously undescribed, rapid body movements. Both species then minimized resistance to turning by bending their bodies to reduce their moment of inertia. Use of this sequential solution by such distantly related animals as an invertebrate and a vertebrate suggests strong selection for these turning dynamics that may extend to other swimmers and inform future vehicle designs.
Modeling the control of bacterial infections via antibiotic-induced proviruses
Authors: Clifton Sara M. , Kim Ted , Chandrashekhar Jayadevi H. , O’Toole George A. , Rapti Zoi , Whitaker Rachel J. 
Published: July 2019

Most bacteria and archaea are infected by latent viruses that change their physiology and responses to environmental stress. We use a population model of the bacteria-phage relationship to examine the role that latent phage play on the bacterial population over time in response to antibiotic treatment. We demonstrate that the stress induced by antibiotic administration, even if bacteria are resistant to killing by antibiotics, is sufficient to control the infection under certain conditions. This work expands the breadth of understanding of phage-antibiotic synergy to include both temperate and chronic viruses persisting in their latent form in bacterial populations.ImportanceAntibiotic-resistance is a growing concern for management of common bacterial infections. Here we show that antibiotics can be effective at sub-inhibitory levels when bacteria carry latent phage. Our findings suggest that specific treatment strategies based on the identification of latent viruses in individual bacterial strains may be an effective personalized medicine approach to antibiotic stewardship.
Selection may oppose invasion, yet favour fixation: consequences for evolutionary stability
Authors: Molina Chai , Earn David J. D. 
Published: July 2019

AbstractModels of evolution by natural selection often make the simplifying assumption that populations are infinitely large. In this infinite population limit, rare mutations that are selected against always go extinct, whereas in finite populations they can persist and even reach fixation. Nevertheless, for mutations of small phenotypic effect, it is widely believed that in sufficiently large populations, if selection opposes the invasion of rare mutants, then it also opposes their fixation. Here, we identify circumstances under which infinite-population models do or do not accurately predict evolutionary outcomes in large, finite populations. We show that there is no population size above which considering only invasion generally suffices: for any finite population size, there are situations in which selection opposes the invasion of mutations of arbitrarily small effect, but favours their fixation. This is not an unlikely limiting case; it can occur when fitness is a smooth function of the evolving trait, and when the selection process is biologically sensible. Nevertheless, there are circumstances under which opposition of invasion does imply opposition of fixation: in fact, for the n-player snowdrift game (a common model of cooperation) we identify sufficient conditions under which selection against rare mutants of small effect precludes their fixation—in sufficiently large populations—for any selection process. We also find conditions under which—no matter how large the population—the trait that fixes depends on the selection process, which is important because any particular selection process is only an approximation of reality.
Simulated Plant Images Improve Maize Leaf Counting Accuracy
Authors: Miao Chenyong , Hoban Thomas P. , Pages Alejandro , Xu Zheng , Rodene Eric , Ubbens Jordan , Stavness Ian , Yang Jinliang , Schnable James C. 
Published: July 2019

ABSTRACTAutomatically scoring plant traits using a combination of imaging and deep learning holds promise to accelerate data collection, scientific inquiry, and breeding progress. However, applications of this approach are currently held back by the availability of large and suitably annotated training datasets. Early training datasets targeted arabidopsis or tobacco. The morphology of these plants quite different from that of grass species like maize. Two sets of maize training data, one real-world and one synthetic were generated and annotated for late vegetative stage maize plants using leaf count as a model trait. Convolutional neural networks (CNNs) trained on entirely synthetic data provided predictive power for scoring leaf number in real-world images. This power was less than CNNs trained with equal numbers of real-world images, however, in some cases CNNs trained with larger numbers of synthetic images outperformed CNNs trained with smaller numbers of real-world images. When real-world training images were scarce, augmenting real-world training data with synthetic data provided improved prediction accuracy. Quantifying leaf number over time can provide insight into plant growth rates and stress responses, and can help to parameterize crop growth models. The approaches and annotated training data described here may help future efforts to develop accurate leaf counting algorithms for maize.
Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders
Authors: Ball G. , Seidlitz J. , Beare R. , Seal M.L. 
Published: July 2019

AbstractCortical development during childhood and adolescence has been characterised in recent years using metrics derived from Magnetic Resonance Imaging (MRI). Changes in cortical thickness are greatest in the first two decades of life and recapitulate the genetic organisation of the cortex, highlighting the potential early impact of gene expression on differences in cortical architecture over the lifespan. It is important to further our understanding of the possible neurobiological mechanisms that underlie these changes as differences in cortical thickness may act as a potential phenotypic marker of several common neurodevelopmental and psychiatric disorders.In this study, we combine MRI acquired from a large typically-developing childhood population (n=768) with comprehensive human gene expression databases to test the hypothesis that disrupted mechanisms common to neurodevelopmental disorders are encoded by genes expressed early in development and nested within those associated with typical cortical remodelling in childhood.We find that differential rates of thinning across the developing cortex are associated with spatially-varying gradients of gene expression. Genes that are expressed highly in regions of accelerated thinning are expressed predominantly in cortical neurons, involved in synaptic remodeling, and associated with common cognitive and neurodevelopmental disorders. Further, we identify subsets of genes that are highly expressed in the prenatal period and jointly associated with both developmental cortical morphology and neurodevelopmental disorders.
Lysine demethylase 7a regulates the anterior-posterior development in mouse by modulating the transcription ofHoxgene cluster
Authors: Higashijima Yoshiki , Nagai Nao , Kitazawa Taro , Kawamura Yumiko , Taguchi Akashi , Nakada Natsuko , Nangaku Masaomi , Furukawa Tetsushi , Aburatani Hiroyuki , Kurihara Hiroki , Wada Youichiro , Kanki Yasuharu 
Published: July 2019

SUMMARYTemporal and spatial colinear expression of theHoxgenes determines the specification of positional identities during vertebrate development. Post-translational modifications of histones contribute to transcriptional regulation. Lysine demethylase 7A (Kdm7a) demethylates lysine 9 di-methylation of histone H3 (H3K9me2) and participates in the transcriptional activation of developmental genes. However, the role of Kdm7a during mouse embryonic development remains to be elucidated. Here, we show thatKdm7a−/−mouse exhibits an anterior homeotic transformation of the axial skeleton, including an increased number of presacral elements. Importantly, posteriorHoxgenes (caudally fromHox9) are specifically downregulated in theKdm7a−/−embryo, which correlates with increased levels of H3K9me2. These observations suggest that Kdm7a controls the transcription of posteriorHoxgenes, likely via its demethylating activity, and thereby regulating the murine anterior-posterior development. Such epigenetic regulatory mechanisms may be harnessed for the proper control of coordinate body patterning in vertebrates.
Activation of the Extracytoplasmic Function σ factor σPby β-lactams inBacillus thuringiensisrequires the site-2 protease RasP
Authors: Ho Theresa D. , Nauta Kelsie M. , Müh Ute , Ellermeier Craig D. 
Published: July 2019

AbstractBacteria can utilize alternative σ factors to regulate sets of genes in response to changes in the environment. The largest and most diverse group of alternative σ factors are the Extracytoplasmic Function (ECF) σ factors. σPis an ECF σ factor found inBacillus anthracis,B. cereus, andB. thuringiensis. Previous work showed σPis induced by ampicillin, a β-lactam antibiotic, and required for resistance to ampicillin. However, it was not known how activation of σPis controlled or what other antibiotics may activate σP. Here we report that activation of σPis specific to a subset of β-lactams and σPis required for resistance to these β-lactams. We demonstrate that activation of σPis controlled by the proteolytic destruction of the anti-σ factor, RsiP, and that degradation of RsiP requires multiple proteases. Upon exposure to β-lactams, the extracellular domain of RsiP is cleaved by an unknown protease, which we predict cleaves at site-1. Following cleavage by the unknown protease, the N-terminus of RsiP is further degraded by the site-2 intramembrane protease, RasP. Our data indicate that RasP cleavage of RsiP is not the rate-limiting step in σPactivation. This proteolytic cascade leads to activation of σPwhich induces resistance to β-lactams likely via increased expression of β-lactamases.ImportanceThe discovery of antibiotics to treat bacterial infections has had a dramatic and positive impact on human health. However, shortly after the introduction of a new antibiotic bacteria often develop resistance. The bacterial cell envelope is essential for cell viability and is the target of many of the most commonly used antibiotics including β-lactam antibiotics. Resistance to β-lactams is often dependent upon β-lactamases. InB. cereus,B. thuringiensisand someB. anthracisstrains the expression of some β-lactamases is inducible. This inducible β-lactamase expression is controlled by activation of an alternative σ factor called σP. Here we show that β-lactam antibiotics induce σPactivation by degradation of the anti-σ factor RsiP.
A Na2CO3-responsive chitinase gene fromChinese wildryeimprove pathogen resistance and saline-alkali stress tolerance in transgenic tobacco and maize
Authors: Liu Xiang-Guo , Yu Ying , Liu Qing , Deng Suren , Jin Xue-Bo , Yin Yue-Jia , Guo Jia , Li Nan , Liu Yang , Han Si-ping , Wang Chuang , Hao Dong-Yun 
Published: July 2019

AbstractSalinity and microbial pathogens are the major limiting factors for crop production. Although the manipulation of many genes could improve plant performance under either of these stresses, few genes have reported that could improve both pathogen resistance and saline-alkali stress tolerance. In this study, we identified a new chitinase geneCHITINASE 2(LcCHI2) that encodes a class II chitinase from a Chinese wildrye (Leymus Chinensis), which grows naturally on alkaline-sodic soil. Overexpression ofLcCHI2increased chitinase activity in transgenic plants. The transgenic tobacco and maize exhibited improved pathogen resistance and enhanced both neutral salt and alkaline salt stress tolerance. Overexpression ofLcCHI2reduced sodium (Na+) accumulation, malondialdehyde content and relative electrical conductivity in transgenic tobacco under salt stress. In addition, the transgenic tobacco showed diminished lesion against bacterial and fungal pathogen challenge, suggesting an improved disease resistance. Similar improved performance was also observed inLcCHI2-overexpressed maize under both pathogen and salt stresses. It is worth noting that this genetic manipulation does not impair the growth and yield of transgenic tobacco and maize under normal cultivation condition. Apparently, application ofLcCHI2provides a new train of thought for genetically engineering saline-alkali and pathogen resistant crops of both dicots and monocots.