bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable centrosomal roots disentangle to allow interphase centriole independence
Authors: Mahen Robert 
Published: October 2017

AbstractThe centrosome is a non-membrane bound cellular compartment consisting of two centrioles surrounded by a protein coat termed the pericentriolar material (PCM). Centrioles must remain physically associated together (a phenomenon called centrosome cohesion) for cell migration, ciliary function and mitosis, yet how this occurs in the absence of a bounding lipid membrane is unclear. One model posits that pericentriolar fibres formed from rootletin protein directly link centrioles, yet little is known about the structure, biophysical properties or assembly kinetics of such fibres. Here, I combine live cell imaging of endogenously tagged rootletin with cell fusion, and find previously unrecognised plasticity in centrosome cohesion. Rootletin forms large, diffusionally stable, bifurcating fibres, which amass slowly on mature centrioles over many hours from anaphase. Nascent centrioles (procentrioles) in contrast do not form roots, and must be licensed to do so through polo-like kinase 1 (PLK1) activity. Transient separation of roots accompanies centriolar repositioning during the interphase, suggesting that centrioles organize as independent units, each containing a discrete root. Indeed, forced induction of duplicate centriole pairs allows independent re-shuffling of individual centrioles between the pairs. Thus, collectively, these findings suggest that progressively nucleated polymers mediate the dynamic association of centrioles as either one or two interphase centrosomes, with implications for our understanding of how non-membrane bound organelles self-organise.
Dynamics and Control of Infections on Social Networks of Population Types
Authors: Williams Brian G. , Dye Christopher 
Published: October 2017

AbstractRandom mixing in host populations has been a convenient simplifying assumption in the study of epidemics, but neglects important differences in contact rates within and between population groups. For HIV/AIDS, the assumption of random mixing is inappropriate for epidemics that are concentrated in groups of people at high risk, including female sex workers (FSW) and their male clients (MCF), injecting drug users (IDU) and men who have sex with men (MSM). To find out who transmits infection to whom and how that affects the spread and containment of infection remains a major empirical challenge in the epidemiology of HIV/AIDS. Here we develop a technique, based on the routine sampling of infection in linked population groups (a social network of population types), which shows how an HIV/AIDS epidemic in Can Tho Province of Vietnam began in FSW, was propagated mainly by IDU, and ultimately generated most cases among the female partners of MCF (FPM). Calculation of the case reproduction numbers within and between groups, and for the whole network, provides insights into control that cannot be deduced simply from observations on the prevalence of infection. Specifically, theper capitarate of HIV transmission was highest from FSW to MCF, and most HIV infections occurred in FPM, but the number of infections in the whole network is best reduced by interrupting transmission to and from IDU. This analysis can be used to guide HIV/AIDS interventions using needle and syringe exchange, condom distribution and antiretroviral therapy. The method requires only routine data and could be applied to infections in other populations.
Continuous interdomain orientation distributions reveal components of binding thermodynamics
Authors: Qi Yang , Martin Jeffrey W. , Barb Adam W. , Thélot François , Yan Anthony , Donald Bruce R. , Oas Terrence G. 
Published: October 2017

1AbstractThe flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings (RDCs), represented as a continuous conformational distribution, and visualized using the disk-on-sphere (DoS) representation. Using the DoS representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions. This analysis also can be extended to multiple probability density modes, using a Bingham mixture model. We use this new paradigm to study the interdomain motions of staphylococcal protein A, which is a key virulence factor contributing to the pathogenicity ofS. aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing components of binding thermodynamics. Such insights allow the dissection the dynamic structural components of functionally important intermolecular interactions.
Improving the visualisation, interpretation and analysis of two-sample summary data Mendelian randomization via the radial plot and radial regression
Authors: Bowden Jack , Spiller Wesley , Greco-M F Fabiola Del , Sheehan Nuala , Thompson John , Minelli Cosetta , Davey Smith George 
Published: October 2017

AbstractBackgroundSummary data furnishing a two-sample Mendelian randomization study are often visualized with the aid of a scatter plot, in which single nucleotide polymorphism (SNP)-outcome associations are plotted against the SNP-exposure associations to provide an immediate picture of the causal effect estimate for each individual variant. It is also convenient to overlay the standard inverse variance weighted (IVW) estimate of causal effect as a fitted slope, to see whether an individual SNP provides evidence that supports, or conflicts with, the overall consensus. Unfortunately, the traditional scatter plot is not the most appropriate means to achieve this aim whenever SNP-outcome associations are estimated with varying degrees of precision and this is reflected in the analysis.MethodsWe propose instead to use a small modification of the scatter plot - the Galbraith radial plot - for the presentation of data and results from an MR study, which enjoys many advantages over the original method. On a practical level it removes the need to recode the genetic data and enables a more straightforward detection of outliers and influential data points. Its use extends beyond the purely aesthetic, however, to suggest a more general modelling framework to operate within when conducting an MR study, including a new form of MR-Egger regression.ResultsWe illustrate the methods using data from a two-sample Mendelian randomization study to probe the causal effect of systolic blood pressure on coronary heart disease risk, allowing for the possible effects of pleiotropy. The radial plot is shown to aid the detection of a single outlying variant which is responsible for large differences between IVW and MR-Egger regression estimates. Several additional plots are also proposed for informative data visualisation.ConclusionThe radial plot should be considered in place of the scatter plot for visualising, analysing and interpreting data from a two-sample summary data MR study. Software is provided to help facilitate its use.
Predicting aging of brain metabolic topography using variational autoencoder
Authors: Choi Hongyoon , Kang Hyejin , Lee Dong Soo ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2017

AbstractPredicting future brain topography can give insight into neural correlates of aging and neurodegeneration. Due to variability in aging process, it has been challenging to precisely estimate brain topographical change according to aging. Here, we predict age-related brain metabolic change by generating future brain18F-Fluorodeoxyglucose PET. A cross-sectional PET dataset of cognitively normal subjects with different age was used to develop a generative model. The model generated PET images using age information and characteristic individual features. Predicted regional metabolic changes were correlated with the real changes obtained by follow-up data. This model was applied to produce a brain metabolism aging movie by generating PET at different ages. Normal population distribution of brain metabolic topography at each age was estimated as well. In addition, a generative model using APOE4 status as well as age as inputs revealed a significant effect of APOE4 status on age-related metabolic changes particularly in the calcarine, lingual cortex, hippocampus and amygdala. It suggested APOE4 could be a factor affecting individual variability in age-related metabolic degeneration in normal elderly. This predictive model may not only be extended to understanding cognitive aging process, but apply to development of a preclinical biomarker for various brain disorders.
Condition-specific series of metabolic sub-networks and its application for gene set enrichment analysis
Authors: Tran Van Du T. , Moretti Sébastien , Coste Alix T. , Amorim-Vaz Sara , Sanglard Dominique , Pagni Marco 
Published: October 2017

AbstractMotivationGenome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organism’s metabolism, yet their integration to achieve biological insight remains challenging.ResultsWe investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set,i.e.a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data forYarrowia lipolyticaand mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO.AvailabilityThemetaboGSER package is available athttps://cran.r-project.org/web/packages/metaboGSE.
Placozoa and Cnidaria are sister taxa
Authors: Laumer Christopher E. , Gruber-Vodicka Harald , Hadfield Michael G. , Pearse Vicki B. , Riesgo Ana , Marioni John C. , Giribet Gonzalo 
Published: October 2017

AbstractThe phylogenetic placement of the morphologically simple placozoans is crucial to understanding the evolution of complex animal traits. Here, we examine the influence of adding new genomes from placozoans to a large dataset designed to study the deepest splits in the animal phylogeny. Using site-heterogeneous substitution models, we show that it is possible to obtain strong support, in both amino acid and reduced-alphabet matrices, for either a sister-group relationship between Cnidaria and Placozoa, or for Cnidaria and Bilateria (=Planulozoa), also seen in most published work to date, depending on the orthologues selected to construct the matrix. We demonstrate that a majority of genes show evidence of compositional heterogeneity, and that the support for Planulozoa can be assigned to this source of systematic error. In interpreting this placozoan-cnidarian clade, we caution against a peremptory reading of placozoans as secondarily reduced forms of little relevance to broader discussions of early animal evolution.
A multi-modal approach to decomposing standard neuropsychological test performance: Symbol Search
Authors: Langer Nicolas , Ho Erica J. , Pedroni Andreas , Alexander Lindsay M. , Marcelle Enitan T. , Schuster Kenneth , Milham Michael P. , Kelly Simon P. 
Published: October 2017

AbstractNeuropsychological test batteries provide normed assessments of cognitive performance across multiple functional domains. Although each test emphasizes a certain component of cognition, a poor score can reflect many possible processing deficits. Here we explore the use of simultaneous eye tracking and EEG to decompose test performance into interpretable, components of cognitive processing. We examine the specific case of Symbol Search, a “processing speed” subtest of the WISC, which involves searching for the presence of either of two target symbols among five search symbols. To characterize the signatures of effective performance of the test, we asked 26 healthy adults to perform a computerized version of it while recording continuous EEG and eye tracking. We first established basic gaze-shifting patterns in the task, such as more frequent and prolonged fixation of each target than each search symbol, and longer search symbol fixations and overall trial duration for target-absent trials. We then entered multiple such metrics into a least absolute shrinkage and selection operator (LASSO) analysis, which revealed that short trial completion times were mainly predicted by longer initial fixations on the targets and fewer subsequent confirmatory saccades directed back to the targets. Further, the tendency to make confirmatory saccades was associated with stronger gamma-amplitude modulation by mid-frontal theta-phase in the EEG during initial target symbol encoding. Taken together, these findings indicate that efficient Symbol Search performance depends more on effective memory encoding than on general “processing speed”.
Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice
Authors: Chamorro-Garcia Raquel , Diaz-Castillo Carlos , Shoucri Bassem M , Käch Heidi , Leavitt Ron , Shioda Toshi , Blumberg Bruce 
Published: October 2017

AbstractAncestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants. This transgenerational inheritance has significant implications for understanding disease etiology. The obesogen hypothesis proposes that exposure to obesogenic chemicals can lead to increased adiposity,in vivo. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the F4 obesity is consistent with a leptin resistant, "thrifty phenotype". Ancestral TBT exposure induces global changes in DNA methylation together with altered expression of metabolism-relevant genes when the F4 animals were exposed to dietary challenges. Analysis of chromatin accessibility in F3 and F4 sperm reveal significant differences between control and TBT groups and significant similarities between F3 and F4 TBT groups that overlap with areas of differential methylation in F4 adipose tissue. Taken together, our data suggest that ancestral TBT exposure induces changes in higher order chromatin organization transmissible through meiosis and mitosis.Non-technical summaryAncestral obesogen exposure in mice causes obesity in untreated F4 male descendants by inducing heritable changes in genome architecture that predispose these animals to become obese when dietary fat is increased modestly. This result is consistent with these animals having a leptin-resistant, "thrifty" phenotype
Gene duplicates cause hybrid lethality between sympatric species ofMimulus
Authors: Zuellig Matthew P. , Sweigart Andrea L. 
Published: October 2017

AbstractHybrid incompatibilities play a critical role in the evolution and maintenance of species. We have discovered a simple genetic incompatibility that causes lethality in hybrids between two closely related species of yellow monkeyflower (Mimulus guttatusandM. nasutus). This hybrid incompatibility, which causes one sixteenth of F2hybrid seedlings to lack chlorophyll and die shortly after germination, occurs between sympatric populations that are connected by ongoing interspecific gene flow. Using complimentary genetic mapping and gene expression analyses, we show that lethality occurs in hybrids that lack a functional copy of the critical photosynthetic genepTAC14. InM. guttatus, this gene was duplicated, but the ancestral copy is no longer expressed. InM. nasutus, the duplication is missing altogether. As a result, hybrids die when they are homozygous for the nonfunctionalM. guttatuscopy and missing the duplicate fromM. nasutus, apparently due to misregulated transcription of key photosynthetic genes. Our study indicates that neutral evolutionary processes may play an important role in the evolution of hybrid incompatibilities and opens the door to direct investigations of their contribution to reproductive isolation among naturally hybridizing species.Author SummaryHybrid incompatibilities play an important role in speciation, because they act to limit gene flow between species. Identifying the genes that underlie these barriers sheds light on the evolutionary forces and genetic mechanisms that give rise to new species. We identified a reproductive barrier that causes lethality in the F2 offspring of sympatric species of yellow monkeyflower (Mimulus guttatusandM. nasutus). We show that lethality occurs in hybrids that lack a functional copy of the critical photosynthetic genepTAC14. This gene was duplicated inM. guttatus, but the ancestral copy subsequently lost function. InM. nasutus, no duplication occurred. As a consequence, F2 hybrids that are homozygous for non-functionalM. guttatuscopies at one locus and missingM. nasutusduplicates at the other locus completely lack functionalpTAC14and die. Our data indicate that non-functionalization of ancestralpTAC14inM. guttatusoccurred via neutral evolutionary change. These results suggest that neutral evolutionary forces may play an important role in speciation.
IFITM proteins inhibit HIV-1 protein synthesis
Authors: Lee Wing-Yiu Jason , Liang Chen , Sloan Richard D 
Published: October 2017

AbstractInterferon induced transmembrane proteins (IFITMs) inhibit the cellular entry of a broad range of viruses, but it has been suspected that for HIV-1 IFITMs may also inhibit a post-integration replicative step. We show that IFITM expression reduces HIV-1 viral protein synthesis by preferentially excluding viral mRNA transcripts from translation and thereby restricts viral production. Codon-optimization of proviral DNA rescues viral translation, implying that IFITM-mediated restriction requires recognition of viral RNA elements. In addition, we find that expression of the viral accessory protein Nef can help overcome the IFITM-mediated inhibition of virus production. Our studies identify a novel role for IFITMs in inhibiting HIV replication at the level of translation, but show that the effects can be overcome by the lentiviral protein Nef.
The eukaryotic Initiation Factor 6 (eIF6) regulates ecdysone biosynthesis by modulating translation inDrosophila
Authors: Russo Arianna , Gatti Guido , Alfieri Roberta , Pesce Elisa , Soanes Kelly , Ricciardi Sara , Mancino Marilena , Cheroni Cristina , Vaccari Thomas , Biffo Stefano , Calamita Piera 
Published: October 2017

ABSTRACTDuring development, ribosome biogenesis and translation reach peak activities, due to impetuous cell proliferation. Current models predict that protein synthesis elevation is controlled by transcription factors and signalling pathways. Developmental models addressing translation factors overexpression effects are lacking. Eukaryotic Initiation Factor (eIF6) is necessary for ribosome biogenesis and efficient translation.eIF6is a single gene, conserved from yeasts to mammals, suggesting a tight regulation need. We generated aDrosophila melanogaster in vivomodel of eIF6 upregulation, demonstrating a boost in general translation and the shut off of the ecdysone biosynthetic pathway. Translation modulation in S2 cells showed that translational rate and ecdysone biosynthesis are inversely correlated. In vivo, eIF6-driven alterations delayed programmed cell death (PCD), resulting in aberrant phenotypes, partially rescued by ecdysone administration. Our data show that eIF6 triggers a translation program with far-reaching effects on metabolism and development, stressing the driving and central role of translation.
Leaf rolling in maize crops: from leaf scoring to canopy level measurements for phenotyping
Authors: Baret F. , Madec S. , Irfan K. , Lopez J. , Comar A. , Hemmerlé M. , Dutartre D. , Praud S. , Tixier M. H. 
Published: October 2017

AbstractLeaf rolling in maize crops is one of the main plant reactions to water stress that may be visually scored in the field. However, the leaf scoring did not reach the high-throughput desired by breeders for efficient phenotyping. This study investigates the relationship between leaf rolling score and the induced canopy structure changes that may be accessed by high-throughput remote sensing techniques.Results gathered over a field phenotyping platform run in 2015 and 2016 show that leaf starts to roll for the water stressed conditions around 9:00 and reaches its maximum around 15:00. Conversely, genotypes conducted under well watered conditions do not show any significant rolling during the same day. Leaf level rolling was very strongly correlated to canopy structure changes as described by the fraction of intercepted radiationfIPARWSderived from digital hemispherical photography. The changes infIPARWSwere stronly correlated (R2=0.86,n=50) to the leaf level rolling visual score. Further, a very good consistency of the genotype ranking of thefIPARWSchanges during the day was found (ρ=0.62). This study demonstrating the strong coordination between leaf level rolling and its impact on canopy structure changes poses the basis for new high-throughput remote sensing methods to quantify this water stress trait.HighlighThe diurnal dynamics of leaf rolling scored visually is strongly related to canopy structure changes that can be documented using Digital hemispherical photography. Consequences for high-throughput field phenotyping are discussed
Systematic evaluation of statistical methods for identifying looping interactions in 5C data
Authors: Gilgenast Thomas G. , Phillips-Cremins Jennifer E. 
Published: October 2017

SummaryChromosome-Conformation-Capture-Carbon-Copy (5C) is a molecular technology based on proximity ligation that enables high-resolution and high-coverage inquiry of long-range chromatin looping interactions. Computational pipelines for analyzing 5C data involve a series of inter-dependent normalization procedures and statistical methods that markedly influence downstream biological results. A detailed analysis of the trade-offs inherent to all stages of 5C analysis has not been reported, but is essential for understanding the biological basis of looping. Here, we provide a comparative assessment of method performance at each step in the 5C analysis pipeline, including sequencing depth and library complexity correction, bias mitigation, spatial noise reduction, distance-dependent expected and variance estimation, modeling, and loop detection. We present a detailed discussion of methodological advantages/disadvantages at each step and provide a full suite of algorithms, lib5C, to allow investigators to test the range of approaches on their own high-resolution 5C data. Principles learned from our comparative analyses will have broad impact on many other forms of Chromosome-Conformation-Capture-based data, including Hi-C, 4C, and Capture-C.