bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybridization disrupts growth-defense strategies and reveals trade-offs masked in unadmixed populations of a perennial plant
Authors: Fetter Karl C. , Nelson David M. , Keller Stephen R. 
Published: October 2019

ABSTRACTOrganisms are constantly challenged by pathogens and pests which can drive the evolution of growth-defense strategies. Plant stomata are essential for gas-exchange during photosynthesis and conceptually lie at the intersection of the physiological demands of growth and exposure to foliar fungal. Generations of natural selection for locally adapted growth-defense strategies can eliminate variation between traits, potentially masking trade-offs and selection conflicts that may have existed in the past. Hybrid populations offer a unique opportunity to reset the clock on selection and to study potentially maladaptive trait variation before selection removes it. We study the interactions of growth, stomatal, ecopysiological, and disease resistance traits in Poplars(Populus)after infection by the leaf rustMelampsora medusae.Phenotypes were measured in a common garden and genotyped at 227K SNPs. We isolate the effects of hybridization on trait variance, discover correlations between stomatal, ecophysiology and disease resistance, examine trade-offs and selection conflicts, and explore the evolution of growth-defense strategies potentially mediated by selection for stomatal traits on the upper leaf surface. These results suggest an important role for stomata in determining growth-defense strategies in organisms susceptible to foliar pathogens, and reinforces the contribution of hybridization studies towards our understanding of trait evolution.
Implications of Immune-Mediated Metastatic Growth on Metastatic Dormancy, Blow-Up, Early Detection, and Treatment
Authors: Rhodes Adam , Hillen Thomas 
Published: October 2019

AbstractMetastatic seeding of distant organs can occur in the very early stages of primary tumor development. Once seeded, these micrometastases may enter a dormant phase that can last decades. Curiously, the surgical removal of the primary tumor can stimulate the accelerated growth of distant metastases, a phenomenon known asmetastatic blow-up. Although several theories have been proposed to explain metastaticdormancyandblow-up, most mathematical investigations have ignored the important pro-tumor effects of the immune system. In this work, we address that shortcoming by developing an ordinary differential equation model of the immune-mediated theory of metastasis. We include both anti- and pro-tumor immune effects, in addition to the experimentally observed phenomenon of tumor-induced immune cell phenotypic plasticity. Using geometric singular perturbation analysis, we derive a rather simple model that captures the main processes and, at the same time, can be fully analyzed. Literature-derived parameter estimates are obtained, and model robustness is demonstrated through a sensitivity analysis. We determine conditions under which the parameterized model can successfully explain both metastatic dormancy and blow-up. Numerical simulations suggest a novel measure to predict the occurrence of future metastatic blow-up, in addition to new potential avenues for treatment of clinically undetectable micrometastases.
Short-term circulating tumor cell dynamics in mouse xenograft models and implications for liquid biopsy
Authors: Williams Amber L. , Fitzgerald Jessica E. , Ivich Fernando , Sontag Eduardo D. , Niedre Mark 
Published: October 2019

AbstractMotivationCirculating tumor cells (CTCs) are widely studied using liquid biopsy methods that analyze single, fractionally-small peripheral blood (PB) samples. However, little is known about fluctuations in CTC numbers that occur over short timescales in vivo, and how these may affect accurate enumeration from blood samples.MethodsWe recently developed an instrument called ‘diffuse in vivo flow cytometry’ (DiFC) that allows continuous, non-invasive counting of rare, green fluorescent protein expressing CTCs in large deeply-seated blood vessels in mice. Here, we used DiFC to study short-term changes in CTC numbers in multiple myeloma and Lewis lung carcinoma xenograft models. We analyzed 35- to 50-minute data sets, with intervals corresponding to approximately 1, 5, 10 and 20% of the PB volume, as well as changes over 24-hour periods.ResultsFor rare CTCs, the use of short DiFC intervals (corresponding to small PB samples) frequently resulted in no detections. For more abundant CTCs, CTC numbers frequently varied by an order of magnitude or more over the time-scales considered. This variability far exceeded that expected by Poisson statistics, and instead was consistent with rapidly changing mean numbers of CTCs in the PB.ConclusionsBecause of these natural temporal changes, accurately enumerating CTCs from fractionally small blood samples is inherently problematic. The problem is likely to be compounded for multicellular CTC clusters or specific CTC subtypes. However, we also show that enumeration can be improved by averaging multiple samples, analysis of larger volumes, or development of new methods for enumeration of CTCs directly in vivo.
Replaying the evolutionary tape to investigate subgenome dominance in allopolyploid Brassica napus
Authors: Bird Kevin A. , Niederhuth Chad , Ou Shujun , Gehan Malia , Pires J. Chris , Xiong Zhiyong , VanBuren Robert , Edger Patrick P. 
Published: October 2019

AbstractInterspecific hybridization and allopolyploidization merges evolutionarily distinct parental genomes (subgenomes) into a single nucleus. A frequent observation is that one subgenome is “dominant” over the other subgenome, having a greater number of reatined duplicate genes and being more highly expressed. Which subgenome becomes dominantly expressed in allopolyploids remains poorly understood. Here we “replayed the evolutionary tape” with six isogenic resynthesized Brassica napus (rapeseed) allopolyploid lines and investigated subgenome dominance patterns over the first ten generations. We found that the same subgenome was consistently more dominantly expressed in all lines and generations. Furthermore, DNA methylation differences between subgenomes mirrored the observed gene expression bias towards the Brassica oleracea derived ‘C’ subgenome in all lines and generations. These differences in gene expression and methylation were also found when comparing the progenitor genomes, suggesting subgenome dominance is related to inherited parental genome differences rather than a byproduct of allopolyploidization. Gene network analyses indicated an enrichment for network interactions and several biological functions for ‘C’ subgenome biased pairs, but no enrichment was observed for ‘A’ subgenome biased pairs. These findings demonstrate that “replaying the evolutionary tape” in allopolyploids results in repeatable and predictable subgenome expression dominance patterns based on preexisting genetic differences among the parental species. These findings have major implications regarding the genotypic and phenotypic diversity observed following plant hybridization in both ecological and agricultural contexts.
Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP signaling pathway in the remodeling of blood vessels
Authors: Yamashiro Yoshito , Thang Bui Quoc , Ramirez Karina , Shin Seung Jae , Kohata Tomohiro , Ohata Shigeaki , Nguyen Tram Anh Vu , Ohtsuki Sumio , Nagayama Kazuaki , Yanagisawa Hiromi 
Published: October 2019

AbstractRationaleThe extracellular matrix (ECM) initiates mechanical cues and transduces intracellular signaling through matrix-cell interactions. In the blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from ECM and how they coordinate with a mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood.ObjectiveThe aim of this study was to elucidate the crucial mediator(s) and molecular signaling pathway(s) involved in matrix mechanotransduction during remodeling of the vessel wall.Methods and ResultsWe performed secretome analysis using rat vascular smooth muscle cells (SMCs) under cyclic stretch and examined matrix-cell interactions and cell behavior. We found that the matricellular protein thrombospondin-1 (Thbs1) was secreted upon cyclic stretch and bound to integrin αvβ1, thereby recruiting vinculin and establishing focal adhesions. RNA-sequence (RNA-seq) analysis revealed that deletion of Thbs1 in vitro markedly affected the target gene expression of Yes-associated protein (YAP). Consistently, we found that Thbs1 promotes nuclear shuttling of YAP in response to cyclic stretch, which depends on the small GTPase Rap2 and Hippo pathway, and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload by transverse aortic constriction (TAC), whereas it suppressed neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall.ConclusionsThbs1 serves as a mechanical stress-triggered extracellular mediator of mechanotransduction that acts via integrin αvβ1 to establish focal adhesions and promotes nuclear shuttling of YAP. We thus propose a novel mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.Subject codesVascular DiseaseGenetically Altered and Transgenic ModelsVascular BiologyCell Signaling/Signal Transduction
Structural conservation and diversity of PilZ-related domains
Authors: Galperin Michael Y. , Chou Shan-Ho 
Published: October 2019

ABSTRACTThe widespread bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a variety of processes, including protein secretion, motility, cell development, and biofilm formation. C-di-GMP-dependent responses are often mediated by its binding to the cytoplasmic receptors that contain the PilZ domain. We present here comparative structural and sequence analysis of various PilZ-related domains and describe three principal types of them: (i) the canonical PilZ domain, whose structure includes a six-stranded beta-barrel and a C-terminal alpha-helix; (ii) an atypical PilZ domain that contains two extra alpha-helices and forms stable tetramers, and (iii) divergent PilZ-related domains, which include the eponymous PilZ protein and PilZN (YcgR_N) and PilZNR (YcgR_2) domains. We refine the second c-di-GMP binding motif of PilZ as [D/N]hSxxG and show that the hydrophobic residue h of this motif interacts with a cluster of conserved hydrophobic residues, helping maintain the PilZ domain fold. We describe several novel PilZN-type domains that are fused to the canonical PilZ domains in specific taxa, such as spirochetes, actinobacteria, cellulosolytic clostridia, deltaproteobacteria, and aquificae. We propose that the evolution of three major groups of PilZ domains included (i) fusion of pilZ with other genes, which produced Alg44, cellulose synthase, and other multidomain proteins; (ii) insertion of a ∼200-bp fragment, which resulted in the formation of tetramer-forming PilZ proteins, and (iii) tandem duplication of pilZ genes, which led to the formation of PilZ dimers and YcgR-like proteins.IMPORTANCECyclic di-GMP is a ubiquitous bacterial second messenger that regulates motility, biofilm formation and virulence of many bacterial pathogens. The PilZ domain is a widespread c-di-GMP receptor that binds c-di-GMP through its RxxxR and [D/N]xSxxG motifs; some PilZ domains lack these motifs and are unable to bind c-di-GMP. We used structural and sequence analysis to assess the diversity of PilZ-related domains and define their common features. We show that the hydrophobic residue h in the second motif is highly conserved; it may serve as a readout for c-di-GMP binding. We describe three principal classes of PilZ-related domains: canonical, tetramer-forming, and divergent PilZ domains, and propose the evolutionary pathways that led to the emergence of these PilZ types.
Difficulties with speech-in-noise perception related to fundamental grouping processes in auditory cortex
Authors: Holmes Emma , Zeidman Peter , Friston Karl J. , Griffiths Timothy D. 
Published: October 2019

AbstractIn our everyday lives, we are often required to follow a conversation when background noise is present (“speech-in-noise” perception). Speech-in-noise perception varies widely—and people who are worse at speech-in-noise perception are also worse at fundamental auditory grouping, as assessed by figure-ground tasks. Here, we examined the cortical processes that link difficulties with speech-in-noise perception to difficulties with figure-ground perception using functional magnetic resonance imaging (fMRI). We found strong evidence that the earliest stages of the auditory cortical hierarchy (left core and belt areas) are similarly disinhibited when speech-in-noise and figure-ground tasks are more difficult (i.e., at target-to-masker ratios corresponding to 60% than 90% thresholds)—consistent with increased cortical gain at lower levels of the auditory hierarchy. Overall, our results reveal a common neural substrate for these basic (figure-ground) and naturally relevant (speech-in-noise) tasks—which provides a common computational basis for the link between speech-in-noise perception and fundamental auditory grouping.
Digitally Deconstructing Leaves in 3D Using X-ray Microcomputed Tomography and Machine Learning
Authors: Théroux-Rancourt Guillaume , Jenkins Matthew R. , Brodersen Craig R. , McElrone Andrew , Forrestel Elisabeth J. , Earles J. Mason 
Published: October 2019

ABSTRACTPremise of the studyX-ray microcomputed tomography (microCT) can be used to measure 3D leaf internal anatomy, providing a holistic view of tissue organisation. Previously, the substantial time needed for segmenting multiple tissues limited this technique to small datasets, restricting its utility for phenotyping experiments and limiting our confidence in the conclusion of these studies due to low replication numbers.Methods and ResultsWe present a Python codebase for random-forest machine learning segmentation and 3D leaf anatomical trait quantification which dramatically reduces the time required to process single leaf microCT scans into detailed segmentations. By training the model on each scan using 6 hand segmented image slices out of >1500 in the full leaf scan, it achieves >90% accuracy in background and tissue segmentation.ConclusionOverall, this 3D segmentation and quantification pipeline can reduce one of the major barriers to using microCT imaging in high-throughput plant phenotyping.
Pregnant women’s understanding and conceptualisations of the harms from drinking alcohol: a qualitative study
Authors: Gibson Sophie , Nagle Cate , Paul Jean , McCarthy Leisa , Muggli Evelyne 
Published: October 2019

AbstractBackgroundDespite women’s awareness that drinking alcohol in pregnancy can lead to lifelong disabilities in a child, it appears that an awareness alone does not discourage some pregnant women from drinking.ObjectivesTo explore influences on pregnant women’s decision making around alcohol use in a population with frequent and heavy peer drinking (i.e. in two Indigenous Australian communities) and another of non-Indigenous pregnant women attending antenatal care in a range of socioeconomic settings.MethodsIndividual and group discussions were held with both Indigenous Australian and non-Indigenous pregnant women attending a variety of antenatal care models, including two Indigenous maternity services in Australia. Data were analysed using inductive content analysis.ResultsA total of 14 Indigenous Australian and 14 non-Indigenous pregnant women participated in this study. Analysis identified five main influences on pregnant women’s alcohol use: the level and detail of women’s understanding of harm; women’s information sources on alcohol use in pregnancy; how this information influenced their choices; how women conceptualised their pregnancy; and whether the social and cultural environment supported abstinence.Conclusions for practiceThis study provides insight into how Indigenous Australian and non-Indigenous pregnant women understand and conceptualise the harms from drinking alcohol, including how their social and cultural environments impact their ability to abstain. Strategies for behaviour change need to: correct misinformation about supposed ‘safe’ timing, quantity and types of alcohol; develop a more accurate perception of Fetal Alcohol Spectrum Disorder; reframe messages about harm to messages about optimising the child’s health and cognitive outcomes; and develop a holistic approach encompassing women’s social and cultural context.
Chromosome organization by one-sided and two-sided loop extrusion
Authors: Banigan Edward J. , van den Berg Aafke A. , Brandão Hugo B. , Marko John F. , Mirny Leonid A. 
Published: October 2019

AbstractSMC complexes, such as condensin or cohesin, organize chromatin throughout the cell cycle by a process known as loop extrusion. SMC complexes reel in DNA, extruding and progressively growing DNA loops. Modeling assuming two-sided loop extrusion reproduces key features of chromatin organization across different organisms. In vitro single-molecule experiments confirmed that yeast condensins extrude loops, however, they remain anchored to their loading sites and extrude loops in a “one-sided” manner. We therefore simulate one-sided loop extrusion to investigate whether “one-sided” complexes can compact mitotic chromosomes, organize interphase domains, and juxtapose bacterial chromosomal arms, as can be done by “two-sided” loop extruders. While one-sided loop extrusion cannot reproduce these phenomena, variants can recapitulate in vivo observations. We predict that SMC complexes in vivo constitute effectively two-sided motors or exhibit biased loading and propose relevant experiments. Our work suggests that loop extrusion is a viable general mechanism of chromatin organization.Impact statementWe reconcile seemingly contradictory findings of single-molecule and in vivo experiments on a major mechanism of chromosome organization by computationally investigating mechanisms of loop extrusion that are consistent with both.
Top-down modulation of neural envelope tracking: the interplay with behavioral, self-report and neural measures of listening effort
Authors: Decruy Lien , Lesenfants Damien , Vanthornhout Jonas , Francart Tom 
Published: October 2019

AbstractWhen listening to natural speech, our neural activity tracks the speech envelope. Moreover, recent research has demonstrated that this neural envelope tracking can be affected by top-down processes. The present study was designed to examine if neural envelope tracking is modulated by the effort that a person expends during listening. Five measures were included to quantify listening effort: two behavioral measures based on a novel dual-task paradigm, a self-report effort measure and two neural measures related to neural phase synchronization and alpha power. Electroencephalography responses to sentences, presented at a wide range of subject-specific signal-to-noise ratios, were recorded in thirteen young, normal-hearing adults. A comparison of the five measures revealed different effects of listening effort as a function of speech understanding. Reaction times on the primary task and self-reported effort decreased with increasing speech understanding. In contrast, reaction times on the secondary task and alpha power showed a peak-shaped behavior with highest effort at intermediate speech understanding levels. We found a positive association between envelope tracking and speech understanding. While a significant effect of listening effort was found on theta-band envelope tracking, the effect size was negligible. Therefore, our results suggest that listening effort is not a confound when using envelope tracking to objectively measure speech understanding in young, normal-hearing adults.
A Multicellular Network Mechanism for Temperature-Robust Food Sensing
Authors: Patel Dhaval S. , Diana Giovanni , Entchev Eugeni V. , Zhan Mei , Lu Hang , Ch’ng QueeLim 
Published: October 2019

AbstractResponsiveness to external cues is a hallmark of biological systems. In complex environments, organisms must remain responsive to specific inputs even as other internal or external factors fluctuate. Here we show how Caenorhabditis elegans can discriminate between food levels to modulate lifespan despite temperature perturbations. While robustness of fixed outputs has been described, our findings uncover a more complex robustness process that maintains food-responsiveness. This end-to-end robustness from environment to physiology is mediated by food-sensing neurons that communicate via TGF-β and serotonin signals to form a multicellular gene network. Mechanistically, specific regulations in this network change with temperature to maintain similar food-responsiveness in the lifespan output. Together, our findings provide a basis for gene-environment interactions and unveil computations that integrate environmental cues to govern physiology.
Determining the association between regionalisation of cortical morphology and cognition in 10,145 children
Authors: Palmer C E , Zhao W , Loughnan R , Zou J , Fan C C , Thompson W K , Jernigan T L , Dale A M 
Published: October 2019

ABSTRACTIndividuals undergo protracted changes in cortical morphology during childhood and adolescence, coinciding with cognitive development. Studies quantifying the association between brain structure and cognition do not always assess regional cortical morphology relative to global brain measures and typically rely on mass univariate statistics or ROI-based analyses. After controlling for global brain measures, it is possible to detect a residual regionalisation pattern indicating the size or thickness of different regions relative to the total cortical surface area or mean thickness. Individual variability in regionalisation may be important for understanding and predicting between subject variability in cognitive performance. Here we sought to determine whether the relative configuration of cortical architecture across the whole cortex was associated with cognition using a novel multivariate omnibus statistical test (MOSTest) in 10,145 children aged 9-10 years from the Adolescent Brain and Cognitive Development (ABCD) Study. MOSTest is better powered to detect associations that are widely distributed across the cortex compared to methods that assume sparse associations. We then quantified the magnitude of the association between vertex-wise cortical morphology and cognitive performance using a linear weighted sum across vertices, based on the estimated vertex-wise effect sizes. We show that the relative pattern of cortical architecture, after removing the effects of global brain measures, predicted unique variance associated with cognition across different imaging modalities and cognitive domains.SIGNIFICANCE STATEMENTThis paper demonstrates a significant advance in our understanding of the relationship between cortical morphology and individual variability in cognition. There is increasing evidence that brain-behaviour associations are distributed across the cortex. Using the unprecedented sample from the Adolescent Brain and Cognitive Development (ABCD) study and a novel application of a multivariate statistical approach (MOSTest), we have discovered specific distributed regionalization patterns across the cortex associated with cognition across multiple cognitive domains. This furthers our understanding of the relationship between brain structure and cognition, namely that these associations are not sparse and localized as assumed with traditional neuroimaging analyses. This multivariate method is extremely versatile and can be used in several different applications.