bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of drought tolerance on guinea grass by dry alginate macrobeads as inoculant of Bacillus strains
Authors: Mendoza-Labrador Jonathan , Romero-Perdomo Felipe , Hernández Juan-Pablo , Uribe Daniel , Buitrago Ruth Bonilla 
Published: September 2019

AbstractDrought is responsible for almost 70% of total crop damage in tropical and subtropical countries. In the Colombian Caribbean, drought has caused low availability of Guinea grass (Megathyrsus maximus) in forage amount and quality, generating increase in production costs in livestock systems. In this study, we aimed at designing and evaluating dry macro-polymeric inoculants of Bacillus strains and used them successfully to mitigate drought effect on Guinea grass (M. maximus). We chose Bacillus sp XT13 and Bacillus megaterium XT14 strains, previously selected for their capacity to mitigate drought stress on Guinea grass. For the inoculant formulation process, a concentration of 3.2% alginate was used for both microorganisms, selecting the polymer-bacterium ratio of 70:30 for XT13 and 80:20 for XT14. The results of the experiments in greenhouse showed that drought had a negative effect on Guinea grass growth, but the PGPB application with or without macro-polymeric dry matrix improved plant growth significantly. We also observed that co-inoculation of the strains generated a greater beneficial effect than individual inoculation. Interestingly, co-inoculation of XT13 and XT14 under the dry macro-polymeric formulation increased biomass production of the aerial part (7.32%), root biomass, (25.3%), nutritional quality parameters, such as digestibility (3.32%), protein (20.3%); proline accumulation increased (21.06%) and both neutral digestible fiber (2.43%) and APX antioxidant activity (24.2%) decreased with respect to co-inoculation of both bacteria without formulation. These findings have shown that dry macrobeads immobilization has a significantly positive influence on the capacity of XT13 and XT14 bacterial strains to induce drought stress tolerance in Guinea grass.
KDML: a machine-learning framework for inference of multi-scale gene functions from genetic perturbation screens
Authors: Sailem Heba Z. , Rittscher Jens , Pelkmans Lucas 
Published: September 2019

AbstractCharacterising context-dependent gene functions is crucial for understanding the genetic bases of health and disease. To date, inference of gene functions from large-scale genetic perturbation screens is based on ad-hoc analysis pipelines involving unsupervised clustering and functional enrichment. We present Knowledge-Driven Machine Learning (KDML), a framework that systematically predicts multiple functions for a given gene based on the similarity of its perturbation phenotype to those with known function. As proof of concept, we test KDML on three datasets describing phenotypes at the molecular, cellular and population levels, and show that it outperforms traditional analysis pipelines. In particular, KDML identified an abnormal multicellular organisation phenotype associated with the depletion of olfactory receptors and TGFβ and WNT signalling genes in colorectal cancer cells. We validate these predictions in colorectal cancer patients and show that olfactory receptors expression is predictive of worse patient outcome. These results highlight KDML as a systematic framework for discovering novel scale-crossing and clinically relevant gene functions. KDML is highly generalizable and applicable to various large-scale genetic perturbation screens.
Selfing Maintains Flower Colour Polymorphism inL. arvensisDespite High Inbreeding Depression
Authors: Jiménez-López Francisco Javier , Ortiz Pedro Luis , Talavera María , Arista Montserrat 
Published: September 2019

AbstractFlower colour polymorphism (FCP) is frequently associated with differences in pollinator attraction. FCP maintenance is intriguing, as positive directional selection by pollinators should result in the loss of polymorphism. Autonomous selfing could confer reproductive assurance when pollen is limited, and could be a mechanism for maintaining polymorphism unless inbreeding depression is high. We study the role of selfing in maintaining FCP inLysimachia arvensis, a species with blue and red morphs co-occurring in Mediterranean populations, where pollinators negatively select for the red morph. We experimentally assessed inbreeding depression in both morphs in two Mediterranean populations and genetic diversity was studied via AFLP and SSR microsatellites in 20 populations. Between-morph genetic differentiation was high and the red morph had a lower genetic diversity, mainly in the Mediterranean. Results also show strong phenological differences between selfed and outcrossed progeny, and a high ID of the red morph. The low genetic diversity of the red morph is in concordance with a reproductive system based predominantly on selfing. However, ID suggests a limited capacity for red morph recruitment, according to its low frequency in polymorphic populations. Genetic differentiation between morphs indicates a low gene flow between them, opening the possibility of reproductive isolation and speciation inLysimachia arvensis.
Interrogation of Enhancer Function by Enhanced CRISPR Epigenetic Editing
Authors: Li Kailong , Liu Yuxuan , Cao Hui , Zhang Yuannyu , Gu Zhimin , Liu Xin , Yu Andy , Kaphle Pranita , Dickerson Kathryn E. , Ni Min , Xu Jian 
Published: September 2019

ABSTRACTTissue-specific gene expression requires coordinated control of gene-proximal and -distalcis-regulatory elements (CREs), yet functional analysis of gene-distal CREs such as enhancers remains challenging. Here we describe enhanced CRISPR/dCas9-based epigenetic editing systems, enCRISPRa and enCRISPRi, for multiplexed analysis of enhancer functionin situandin vivo. Using dual effectors capable of re-writing enhancer-associated chromatin modifications, we show that enCRISPRa and enCRISPRi modulate gene transcription by remodeling local epigenetic landscapes at sgRNA-targeted enhancers and associated genes. Comparing with existing methods, the new systems display more robust perturbation of enhancer activity and gene transcription with minimal off-targets. Allele-specific targeting of enCRISPRa to oncogenicTAL1super-enhancer modulatesTAL1expression and cancer progression in xenotransplants. Multiplexed perturbations of lineage-specific enhancers using an enCRISPRi knock-in mouse establishin vivoevidence for lineage-restricted essentiality of developmental enhancers during hematopoietic lineage specification. Hence, enhanced CRSIPR epigenetic editing provides opportunities for interrogating enhancer function in native biological contexts.
Trophic Selective Pressures Organize the Composition of Endolithic Microbial Communities from Global Deserts
Authors: Qu Evan , Omelon Chris , Oren Aharon , Meslier Victoria , Cowan Don A. , Maggs-Kölling Gillian , DiRuggiero Jocelyne 
Published: September 2019

AbstractStudies of microbial biogeography are often convoluted by extremely high diversity and differences in microenvironmental factors such as pH and nutrient availability. Desert endolithic (inside rock) communities are exceptionally simple ecosystems that can serve as a tractable model for investigating long-range biogeographic effects on microbial communities. We conducted a comprehensive survey of endolithic sandstones using high-throughput marker gene sequencing to characterize global patterns of diversity in endolithic microbial communities. We also tested a range of abiotic variables in order to investigate the factors that drive community assembly at various trophic levels. Macroclimate was found to be the primary driver of endolithic community composition, with the most striking difference witnessed between hot and polar deserts. This difference was largely attributable to the specialization of prokaryotic and eukaryotic primary producers to different climate conditions. On a regional scale, microclimate and properties of the rock substrate were found to influence community assembly, although to a lesser degree than global hot versus polar conditions. We found new evidence that the factors driving endolithic community assembly differ between trophic levels. While phototrophic taxa were rigorously selected for among different sites, heterotrophic taxa were more cosmopolitan, suggesting that stochasticity plays a larger role in heterotroph assembly. This study is the first to uncover the global drivers of desert endolithic diversity using high-throughput sequencing. We demonstrate that phototrophs and heterotrophs in the endolithic community assemble under different stochastic and deterministic influences, emphasizing the need for studies of microorganisms in context of their functional niche in the community.
Corona exchange dynamics on carbon nanotubes by multiplexed fluorescence monitoring
Authors: Pinals Rebecca L. , Yang Darwin , Lui Alison , Cao Wendy , Landry Markita P. 
Published: September 2019

ABSTRACTNoncovalent adsorption of DNA on nanoparticles has led to their widespread implementation as gene delivery tools and optical probes. Yet, the behavior and stability of DNA-nanoparticle complexes once applied in biomolecule-rich,in vivoenvironments remains unpredictable, whereby biocompatibility testing usually occurs in serum. Here, we demonstrate time-resolved measurements of exchange dynamics between solution-phase and adsorbed corona-phase DNA and protein biomolecules on single-walled carbon nanotubes (SWCNTs). We capture real-time binding of fluorophore-labeled biomolecules, utilizing the SWCNT surface as a fluorescence quencher, and apply this corona exchange assay to study protein corona dynamics on ssDNA-SWCNT-based dopamine sensors. We study exchange of two blood proteins, albumin and fibrinogen, adsorbing to and competitively displacing (GT)6vs. (GT)15ssDNA from ssDNA-SWCNTs. We find that (GT)15binds to SWCNTs with a higher affinity than (GT)6and that fibrinogen interacts with ssDNA-SWCNTs more strongly than albumin. Albumin and fibrinogen cause a 52.2% and 78.2% attenuation of the dopamine nanosensor response, coinciding with 0.5% and 3.7% desorption of (GT)6, respectively. Concurrently, the total surface-adsorbed fibrinogen mass is 168% greater than that of albumin. Binding profiles are fit to a competitive surface exchange model which recapitulates the experimental observation that fibrinogen has a higher affinity for SWCNTs than albumin, with a fibrinogen on-rate constant 1.61-fold greater and an off-rate constant 0.563-fold smaller than that of albumin. Our methodology presents a generic route to assess real-time corona exchange on nanoparticles in solution phase, and more broadly motivates testing of nanoparticle-based technologies in blood plasma rather than the more ubiquitously-tested serum conditions.
Transmission analysis of a large TB outbreak in London: mathematical modelling study using genomic data
Authors: Xu Yuanwei , Topliffe Hollie , Stimson James , Stagg Helen R. , Abubakar Ibrahim , Colijn Caroline 
Published: September 2019

AbstractOutbreaks of tuberculosis- such as the large isoniazid-resistant outbreak centered on London, United Kingdom, which originated in 1995- provide excellent opportunities to model transmission of this devastating disease. Transmission chains for tuberculosis are notoriously difficult to ascertain, but mathematical modelling approaches, combined with whole-genome sequencing (WGS) data, have strong potential to contribute to transmission analyses. Using such data, we aimed to reconstruct transmission histories for the outbreak using a Bayesian approach, and to use machine learning techniques with patient-level data to identify the key covariates associated with transmission. By using our transmission reconstruction method that accounts for phylogenetic uncertainty, we are able to identify 24 transmission events with reasonable confidence, 11 of which have zero single nucleotide polymorphism (SNP) distance, and as maximum distance of 3. Patient age, alcohol abuse and history of homelessness were found to be the most important predictors of being credible tuberculosis transmitters.
BrainSpace: a toolbox for the analysis of macroscale gradients in neuroimaging and connectomics datasets
Authors: de Wael Reinder Vos , Benkarim Oualid , Paquola Casey , Lariviere Sara , Royer Jessica , Tavakol Shahin , Xu Ting , Hong Seok-Jun , Valk Sofie L. , Misic Bratislav , Milham Michael P. , Margulies Daniel S. , Smallwood Jonathan , Bernhardt Boris C. 
Published: September 2019

AbstractUnderstanding how higher order cognitive function emerges from the underlying brain structure depends on quantifying how the behaviour of discrete regions are integrated within the broader cortical landscape. Recent work has established that this macroscale brain organization and function can be quantified in a compact manner through the use of multivariate machine learning approaches that identify manifolds often described as cortical gradients. By quantifying topographic principles of macroscale organization, cortical gradients lend an analytical framework to study structural and functional brain organization across species, throughout development and aging, and its perturbations in disease. More generally, its macroscale perspective on brain organization offers novel possibilities to investigate the complex relationships between brain structure, function, and cognition in a quantified manner. Here, we present a compact workflow and open-access toolbox that allows for (i) the identification of gradients (from structural or functional imaging data), (ii) their alignment (across subjects or modalities), and (iii) their visualization (in embedding or cortical space). Our toolbox also allows for controlled association studies between gradients with other brain-level features, adjusted with respect to several null models that account for spatial autocorrelation. The toolbox is implemented in both Python and Matlab, programming languages widely used by the neuroimaging and network neuroscience communities. Several use-case examples and validation experiments demonstrate the usage and consistency of our tools for the analysis of functional and microstructural gradients across different spatial scales.
A viral fusogen hijacks the actin cytoskeleton to drive cell-cell fusion
Authors: Chan Ka Man Carmen , Son Sungmin , Schmid Eva M. , Fletcher Daniel A. 
Published: September 2019

AbstractCell-cell fusion, which is essential for tissue development and used by some viruses to form pathological syncytia, is typically driven by fusogenic membrane proteins with tall (>10 nm) ectodomains that undergo conformational changes to bring apposing membranes in close contact prior to fusion. Here we report that a viral fusogen with a short (<2 nm) ectodomain, the reptilian orthoreovirus p14, accomplishes the same task by hijacking the actin cytoskeleton. We show that the cytoplasmic domain of p14 triggers N-WASP-mediated assembly of a branched actin network, directly coupling local force generation with a short membrane-disruptive ectodomain. This work reveals that overcoming energetic barriers to cell-cell fusion does not require conformational changes of tall fusogens but can instead be driven by harnessing the host cytoskeleton.Impact StatementA viral fusogen drives cell-cell fusion by hijacking the actin machinery to directly couple actin assembly with a short fusogenic ectodomain.
Constructing and Forgetting Temporal Context in the Human Cerebral Cortex
Authors: Chien Hsiang-Yun Sherry , Honey Christopher J. 
Published: September 2019

SummaryHow does information from seconds earlier affect neocortical responses to new input? Here, we used empirical measurements and computational modeling to study the integration and forgetting of prior information. We found that when two groups of participants heard the same sentence in a narrative, preceded by different contexts, the neural responses of each group were initially different, but gradually fell into alignment. We observed a hierarchical gradient: sensory cortices aligned most quickly, followed by mid-level regions, while higher-order cortical regions aligned last. In some higher order regions, responses to the same sentence took more than 10 seconds to align. What kinds of computations can explain this hierarchical organization of contextual alignment? Passive linear integration models predict that regions which are slower to integrate new information should also be slower to forget old information. However, we found that higher order regions could rapidly forget prior context. The data were better captured by a model composed of hierarchical autoencoders in time (HAT). In HAT, cortical regions maintain a temporal context representation which is actively integrated with input at each moment, and this integration is gated by prediction error. These data and models suggest that sequences of information are combined throughout the cortical hierarchy using an active and gated integration process.
Non-parallel transcriptional divergence during parallel adaptation
Authors: Fischer Eva K , Song Youngseok , Hughes Kimberly A , Zhou Wen , Hoke Kim L 
Published: September 2019

AbstractHow underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high- and low-predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity as well as the evolution of expression plasticity itself across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high- and low-predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.
Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
Authors: Gupta Ashwani K. , Sarkar Prasenjit , Pan Xinchao , Carroll Thomas , Oxburgh Leif 
Published: September 2019

ABSTRACTRecent years have seen rapid advances in directed differentiation of human pluripotent stem cells (PSCs) to kidney cells. However, a fundamental difficulty in emulating kidney tissue formation is that kidney development is iterative. Recent studies argue that the human nephron forms through gradual contribution of nephron progenitor cells whose differentiation fates depend on the time at which they are recruited. We show that the majority of PSC-derived nephron progenitor cells differentiated in a short wave in organoid formation and to improve fidelity of PSC-derived organoids, we emulated the asynchronous mix found in the fetal kidney by combining cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and lineage marking data showed that proximal and distal nephron components preferentially derive from cell populations differentiated at distinct times. When engrafted under the kidney capsule these heterochronic organoids were vascularized and displayed essential features of kidney tissue. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed using intravenous injection of fluorescent dextran. Despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study, and we propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop the same stromal overgrowth when engrafted under the kidney capsule.
Sporadic ERK pulses drive non-genetic resistance in drug-adapted BRAFV600Emelanoma cells
Authors: Gerosa Luca , Chidley Christopher , Froehlich Fabian , Sanchez Gabriela , Lim Sang Kyun , Muhlich Jeremy , Chen Jia-Yun , Baker Gregory J. , Schapiro Denis , Shi Tujin , Yi Lian , Nicora Carrie D. , Claas Allison , Lauffenburger Douglas A. , Qian Wei-Jun , Wiley H. Steven , Sorger Peter K. 
Published: September 2019

SUMMARYAnti-cancer drugs commonly target signal transduction proteins activated by mutation. In patients with BRAFV600Emelanoma, small molecule RAF and MEK kinase inhibitors cause dramatic but often transient tumor regression. Emerging evidence suggests that cancer cells adapting by non-genetic mechanisms constitute a reservoir for the development of drug-resistant tumors. Here, we show that few hours after exposure to RAF/MEK inhibitors, BRAFV600Emelanomas undergo adaptive changes involving disruption of negative feedback and sporadic pulsatile reactivation of the MAPK pathway, so that MAPK activity is transiently high enough in some cells to drive proliferation. Quantitative proteomics and computational modeling show that pulsatile MAPK reactivation is possible due to the co-existence in cells of two MAPK cascades: one driven by BRAFV600Ethat is drug-sensitive and a second driven by receptors that is drug-resistant. Paradoxically, this may account both for the frequent emergence of drug resistance and for the tolerability of RAF/MEK therapy in patients.
The “Locus of Learning” Problem: Effects of Stimulus and Task Structure on Temporal Perceptual Learning
Authors: Xu Rannie , Church Russell M. , Sasaki Yuka , Watanabe Takeo 
Published: September 2019

AbstractThe ability to discriminate sub-second intervals can be improved with practice, a process known as temporal perceptual learning (TPL). A central question in TPL is whether training improves the low-level sensory representation of a temporal interval or optimizes a set of task-specific response strategies. Here, we trained three groups of participants over five days on a single-interval temporal discrimination task using either fixed intervals (FI) or random intervals (RI). Before and after training, discrimination thresholds were also obtained on an untrained task. Our results revealed that only the FI group showed improvements with five days of training, but this learning did not generalize from the trained task to the untrained task in any group. These results highlight task-specificity in TPL and suggest that training-dependent improvements in timing ability might reflect an active reweighting of decision units, in addition to refinements in the sensory representation of a learned interval.