bluuebunny/crossref_metadata_2025 huggingface dataset:
A Description of the Possible Etiology of the Cilantro Yellow Blotch Disease
Authors: Alabi Olufemi J. , Gaytán Brianna C. , Al Rwahnih Maher , Villegas Cecilia
Published: October 2019

A virus-like disease characterized by foliar yellow blotch symptoms and resembling those described for cilantro yellow blotch disease in California was observed in a 4.05-ha cilantro (Coriandrum sativum) cv. Santo field in Hidalgo County, Texas during spring 2019. Disease incidence at harvest was estimated at ∼20%, and the affected plants were rendered unmarketable. Foliar systemic chlorosis symptoms were observed on sap-inoculated Nicotiana occidentalis plants (n = 3) using inocula from symptomatic cilantro. Total RNA aliquots from 11 randomly collected leaf tissue samples (symptomatic = 7, asymptomatic = 4) were pooled into a composite cilantro RNA sample which was analyzed by high throughput sequencing (HTS). Analyses of the obtained 15.7 million raw reads (76 nt each) yielded virus-specific contigs that mapped to the genomes of alfalfa mosaic virus (AMV), beet pseudoyellows virus (BPYV), and lettuce chlorosis virus (LCV). Virus-specific primers designed from the HTS-derived sequences were used to screen the samples in two-step RT-PCR assays, resulting in the detection of AMV+BPYV in 3 of 7 symptomatic cilantro samples, AMV+LCV in 4 of 7 symptomatic cilantro samples, and AMV alone in the 4 asymptomatic cilantro and sap-inoculated N. occidentalis samples. The results represent the first reports of the natural infection of cilantro by BPYV and LCV and implicate the mixed infection of a Crinivirus and AMV in cilantro yellow blotch disease.
A PCR-Based Method for the Rapid Detection ofChondrostereum purpureumin Apple
Authors: Grinbergs D. , Chilian J. , Carrasco-Fernández J. , France A. , Moya-Elizondo E. , Gerding M.
Published: October 2019

Silverleaf caused by the basidiomycete Chondrostereum purpureum affects numerous woody species, including fruit tree crops like apple, resulting in wood necrosis and foliar silvering. There are no curative alternatives for this disease, and its management is by prevention methods. Therefore, the aim of this study was to develop a rapid diagnostic tool for the detection and identification of C. purpureum directly from woody tissues to help distinguish the pathogen from other basidiomycetes that are commonly found on apple. The silverleaf pathogen was isolated from different hosts and locations, and Koch’s postulates were performed by inoculating the isolates on apple cuttings and measuring internal necrosis. A previously described APN 1 pair of primers specificity was also tested against 25 C. purpureum isolates in this study, using other wood rotting species as negative controls. Seven virulent isolates were inoculated on apple cuttings, and DNA was extracted from the cuttings’ sawdust and amplified using APN 1, after 22 days of incubation. To prove the efficiency of the method in the field, DNA from healthy nursery plants inoculated with two virulent isolates, and naturally infected plants showing different levels of foliar symptoms, were tested. Presence of the fungus was verified by reisolation on APDA in all assays. Koch’s postulates indicated that all C. purpureum isolates were pathogenic, showing different virulence levels, and APN 1 primers were able to discriminate them from other basidiomycetes. The method was also able to detect C. purpureum from artificially inoculated plants as well as naturally infected ones, demonstrating that the protocol may become a rapid minimally destructive diagnostic tool to detect the pathogen without the need to isolate it from tissues, and thus taking measures to prevent its dissemination.
The Conditional Probability of Vestibular Schwannoma Growth at Different Time Points After Initial Stability on an Observational Protocol
Authors: Sethi Mantegh , Borsetto Daniele , Cho Yeajoon , Gair Juliette , Gamazo Nicola , Jefferies Sarah , Joannides Alexis , Mannion Richard , Helmy Adel , Axon Patrick , Donnelly Neil , Tysome James R. , Bance Manohar
Published: October 2019

Objective:

The natural history of vestibular schwannomas (VS) is well documented in the literature, with tumour growth being paramount to decision making for both surveillance and treatment of these patients. Most previous studies refer to the risk of VS growth over a given period of time; however, this is not useful for counselling patients at different stages of their follow-up, as the risk of tumour growth is likely to be less following each subsequent year that a tumour does not grow. Accordingly, we investigated the conditional probability of VS growth at particular time-points, given a patient has not grown thus far. This Bayesian method of risk stratification allows for more tailored and accurate approximations of the risk of growth versus nongrowth of VS.

Methods:

Retrospective analysis of a prospectively collected database in a tertiary referral skull base unit, containing all patients diagnosed between 2005 and 2014 with sporadic unilateral VS and a minimum of 5-year surveillance.

Results:

A total of 341 patients met the inclusion criteria. The mean age at diagnosis was 67 years, the sizes of the VS at diagnosis were intracanalicular in 49%, small in 39%, medium in 11%, and large in 1%. Over the entire 5-year surveillance period, a total of 139 tumours were seen to grow (41%) and 202 did not grow (59%). At 1 year, the probability of growth given that the tumour had not grown to date was seen to be 21%, at 2 years 12%, at 3 years 9%, at 4 years 3%, and at 5 years 2%. The conditional probability of growth of extracanalicular VS was significantly higher in the first year when compared with intracanalicular VS (29% versus 13%, p = 0.01), but there was no such difference in years 2, 3, 4 or 5 (p = 0.60, 0.69, 0.36, 0.39, respectively).

Conclusion:

This is the first study in the literature concerned specifically with the conditional probability of VS growth. The data presented here can be used to better inform VS patients of their risk of growth at particular time points in their disease—the longer VS have been observed to be stable, the lower the risk of subsequent growth in a given year. Further, an extracanalicular vestibular schwannoma is more likely to grow in the first year compared with an intracanalicular vestibular schwannoma. Our data also adds support to surveillance protocols with increasingly infrequent MRI scans, as after 4 years of not growing, the risk of growth in year 5 falls to <2%.
Rosette-forming Glioneuronal Tumor in the Optic Pathway of a Child
Authors: Bharadwaj Rishab , Chickabasaviah Yasha T. , Rao Santosh , Srinivasan Arathi , Balasubramaniam Chidambaram , Chandrasekhar Sanjay , Scott Julius X.
Published: October 2019

Rosette-forming glioneuronal tumor is a rare World Health Organization grade I neoplasm, primarily involving the posterior fossa. Most cases have been reported in young adults. Although maximal surgical resection is advocated, a precise treatment modality is yet to be established. We describe an unusual presentation of rosette-forming glioneuronal tumor occurring in the optic pathway in a child. As the site of the tumor was not amenable to resection, he underwent radiotherapy and is currently well on follow-up.
Georhizobium profundi gen. nov., sp. nov., a piezotolerant bacterium isolated from a deep-sea sediment sample of the New Britain Trench
Authors: Cao Junwei , Wei Yuli , Lai Qiliang , Wu Yunjie , Deng Junhao , Li Jianyang , Liu Rulong , Wang Li , Fang Jiasong
Published: October 2019

A novel alphaproteobacterium, strain WS11T, was isolated from a deep-sea sediment sample collected from the New Britain Trench. The full-length 16S rRNA gene of strain WS11T had the highest sequence similarity of 97.6 % to

Rhizobium subbaraonis

JC85T, followed by

Mycoplana ramosa

DSM 7292T (96.9 %) and

Rhizobium azooxidifex

Po 20/26T (96.8 %). Phylogenetic analysis of concatenated 16S rRNA, atpD and recA gene sequences showed that strain WS11T was deeply separated from the species within the family

Rhizobiaceae

. Phylogenomic analysis based on the whole-genome protein sequences showed that strain WS11T formed an independent monophyletic branch in the family

Rhizobiaceae

, paralleled with the species in the families

Brucellaceae

and

Phyllobacteriaceae

within the order

Rhizobial

es. Cells were Gram-stain-negative, oxidase- and catalase-positive, and aerobic short rods (1.5–2.4×0.9–1.0 µm). Growth was observed at salinities ranging from 0 to 5% (optimum, 1 %), from pH 6.5 to 9 (optimum, pH 7) and at temperatures between 20 and 30 °C (optimum, 28 °C). Strain WS11T was piezotolerant, growing optimally at 0.1 MPa (range 0.1–70 MPa). The main fatty acid was summed feature 8 (C18 : 1
ω7c/C18
 : 1
ω
6c). The sole respiratory quinone was ubiquinone-10 (Q-10). The predominant polar lipids were phosphatidylcholine, two unidentified aminophospholipids and an unidentified phospholipid. The genome size was about 4.36 Mbp and the G+C content was 62.3 mol%. The combined genotypic and phenotypic data show that strain WS11T represents a novel species of a novel genus in the family

Rhizobiaceae

, for which the name Georhizobium profundi gen. nov., sp. nov. is proposed (type strain WS11T=MCCC 1K03498T=KCTC 62439T).
Reduced RNA turnover as a driver of cellular senescence
Authors: Mullani Nowsheen , Porozhan Yevheniia , Costallat Mickael , Batsché Eric , Goodhardt Michele , Cenci Giovanni , Mann Carl , Muchardt Christian
Published: October 2019

Accumulation of senescent cells is an important contributor to chronic inflammation upon aging. While cytoplasmic DNA was shown to drive the inflammatory phenotype of senescent cells, an equivalent role for RNA has never been explored. Here, we show that some senescent cells accumulate long promoter RNAs and 3’ gene extensions, rich in retrotransposon sequences. Accordingly, these cells display increased expression of genes involved in detecting double stranded RNA of viral origin downstream of the interferon pathway. The RNA accumulation is correlated with signs of reduced RNA turn-over, including in some cases, reduced expression of RNA exosome subunits. Reciprocally, engineered inactivation of RNA exosome subunit Exosc3 induces expression of multiple senescence markers. A senescence-like RNA accumulation is also observed in cells exposed to oxidative stress, an important trigger of cellular senescence. Altogether, we propose that in a subset of senescent cells, repeat-containing transcripts stabilized by oxidative stress or reduced RNA exosome activity participate, possibly in combination with cytoplasmic DNA, in driving and maintaining the permanent inflammatory state characterizing cellular senescence.
Embryonic organoids recapitulate early heart organogenesis
Authors: Rossi Giuliana , Boni Andrea , Guiet Romain , Girgin Mehmet , Kelly Robert G. , Lutolf Matthias P.
Published: October 2019

Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here we show that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo the fundamental steps of early heart organogenesis with anin vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids support the generation of cardiovascular progenitors, as well as first and second heart field compartments. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a putative primitive gut-like tube, from which it is separated by an endocardial-like layer. These findings unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues. This platform could be an excellent tool for studying heart development in unprecedented detail and throughput.
Genome dashboards: Framework and Examples
Authors: Li Zilong , Sun Ran , Bishop Thomas C.
Published: October 2019

Genomics is a sequence-based informatics science and a 3D structure-based material science. Here we describe a framework for developing genome dashboards specifically designed to unify informatics with studies of chromatin structure and dynamics. The framework is based on the mathematical representation of geometrically exact rod models and the generalization of DNA base pair step parameters. A Model-View-Controller software design approach is proposed to implement genome dashboards as finite state machines either as desktop or web based applications. Two examples are demonstrated using our minimal genome dashboard called G-Dash-min. The data unification achieved with a genome dashboard supports the bi-directional exchange of data between informatics and structure. Thus any experimentally or theoretically determined sequence based informatics track can inform DNA, nucleosome or chromatin modeling (e.g. nucleosome positions) and structure features can be analyzed as informatics tracks in a genome browser (e.g. DNA base pair step parameters: Roll, Tilt, Twist). Here the framework is applied to chromatin, but genome dashboards are more broadly applicable. Genome dashboards are a novel means of investigating structure-function relationships for regions of the genome ranging from base pairs to entire chromosomes and for generating, validating, and testing mechanistic hypotheses.
Population-specific causal disease effect sizes in functionally important regions impacted by selection
Authors: Shi Huwenbo , Gazal Steven , Kanai Masahiro , Koch Evan M. , Schoech Armin P. , Siewert Katherine M. , Kim Samuel S. , Luo Yang , Amariuta Tiffany , Huang Hailiang , Okada Yukinori , Raychaudhuri Soumya , Sunyaev Shamil R. , Price Alkes L.
Published: October 2019

Many diseases and complex traits exhibit population-specific causal effect sizes with trans-ethnic genetic correlations significantly less than 1, limiting trans-ethnic polygenic risk prediction. We developed a new method, S-LDXR, for stratifying squared trans-ethnic genetic correlation across genomic annotations, and applied S-LDXR to genome-wide association summary statistics for 31 diseases and complex traits in East Asians (EAS) and Europeans (EUR) (average NEAS=90K, NEUR=267K) with an average trans-ethnic genetic correlation of 0.85 (s.e. 0.01). We determined that squared trans-ethnic genetic correlation was 0.82× (s.e. 0.01) smaller than the genome-wide average at SNPs in the top quintile of background selection statistic, implying more population-specific causal effect sizes. Accordingly, causal effect sizes were more population-specific in functionally important regions, including conserved and regulatory regions. In analyses of regions surrounding specifically expressed genes, causal effect sizes were most population-specific for skin and immune genes and least population-specific for brain genes. Our results could potentially be explained by stronger gene-environment interaction at loci impacted by selection, particularly positive selection.
From a deep learning model back to the brain - inferring morphological markers and their relation to aging
Authors: Levakov Gidon , Rosenthal Gideon , Shelef Ilan , Raviv Tammy Riklin , Avidan Galia
Published: October 2019

We present a Deep Learning framework for the prediction of chronological age from structural MRI scans. Previous findings associate an overestimation of brain age with neurodegenerative diseases and higher mortality rates. However, the importance of brain age prediction goes beyond serving as biomarkers for neurological disorders. Specifically, utilizing convolutional neural network (CNN) analysis to identify brain regions contributing to the prediction can shed light on the complex multivariate process of brain aging. Previous work examined methods to attribute pixel/voxel-wise contributions to the prediction in a single image, resulting in ‘explanation maps’ that were found noisy and unreliable. To address this problem, we developed an inference framework for combining these maps across subjects, thus creating a population-based rather than a subject-specific map. We applied this method to a CNN ensemble trained on predicting subjects’ age from raw T1 brain images of 10,176 subjects. Evaluating the model on an untouched test set resulted in mean absolute error of 3.07 years and a correlation between chronological and predicted age of r=0.98. Using the inference method, we revealed that cavities containing CSF, previously found as general atrophy markers, had the highest contribution for age prediction. Comparing maps derived from different models within the ensemble allowed to assess differences and similarities in brain regions utilized by the model. We showed that this method substantially increased the replicability of explanation maps, converged with results from voxel-based morphometry age studies and highlighted brain regions whose volumetric variability contributed the most to the prediction.

Highlights

CNNs ensemble is shown to estimate “brain age” from sMRI with an MAE of ∼3.1 years

A novel framework enables to highlight brain regions contributing to the prediction

This framework results in explanation maps showing consistency with the literature

As sample size increases, these maps show higher inter-sample replicability

CSF cavities reflecting general atrophy were found as a prominent aging biomarker
Deep metagenomics examines the oral microbiome during dental caries, revealing novel taxa and co-occurrences with host molecules
Authors: Baker J.L. , Morton J.T. , Dinis M. , Alverez R. , Tran N.C. , Knight R. , Edlund A.
Published: October 2019

Dental caries is the most common chronic infectious disease globally. The microbial communities associated with caries have mainly been examined using relatively low-resolution 16S rRNA gene amplicon sequencing and/or using downstream analyses that are unsound for the compositional nature of the data provided by sequencing. Additionally, the relationship between caries, oral microbiome composition, and host immunological markers has not been explored. In this study, the oral microbiome and a panel of 38 host markers was analyzed across the saliva from 23 children with dentin caries and 24 children with healthy dentition. Metagenomic sequencing, followed by investigation using tools designed to be robust for compositional data, illustrated that severalPrevotellaspp. were prevalent in caries, whileRothiaspp. were associated with the health. The contributional diversity (extent to which multiple taxa contribute to each pathway) of functional pathways present in the oral microbiome was decreased in the caries group. This decrease was especially noticeable in several pathways known to impede caries pathogenesis, including arginine and branched-chain amino acid biosynthesis. 10 host immunological markers were found to be significantly elevated in the saliva of the caries group, and microbe-metabolite co-occurrence analysis provided an atlas of relationships contributing to the bi-directional influence between the oral microbiome and the host immune system. Finally, 527 metagenome-assembled genomes were obtained from the metagenomics data, representing 151 species. 23 taxa were novel genera/species and a further 20 taxa were novel species. This study thus serves as a model analysis pipeline that will tremendously expand our knowledge of the oral microbiome and its relationship to dental caries once applied to large populations.
Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development
Authors: Sen Maya , Mooijman Dylan , Boisset Jean-Charles , Chialastri Alex , Popovic Mina , Heindryckx Björn , de Sousa Lopes Susana M. Chuva , Dey Siddharth S. , van Oudenaarden Alexander
Published: October 2019

DNA methylation (5mC) is central to cellular identity and the global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of terminally differentiated gametes to the pluripotent cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to genome-wide 5mC erasure remains unclear. Here, we report a new high-throughput single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, thereby allowing us to systematically probe the dynamics of global demethylation. First, when applied to hybrid mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity, with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome suggesting loss of maintenance methylation. Next, using scMspJI-seq in preimplantation mouse embryos, we discovered that methylation maintenance is active till the 16-cell stage followed by passive demethylation in a fraction of cells within the early blastocyst at the 32-cell stage of development. Finally, we found that human preimplantation embryos qualitatively show temporally delayed yet similar demethylation dynamics as mouse preimplantation embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost-effective method to map the strand-specific genome-wide patterns of 5mC in single cells, thereby enabling quantitative investigation of methylation dynamics in developmental systems.
In pursuit of visual attention: SSVEP frequency-tagging moving targets
Authors: de Lissa Peter , Caldara Roberto , Nicholls Victoria , Miellet Sebastien
Published: October 2019

Previous research has shown that visual attention does not always exactly follow gaze direction, leading to the concepts of overt and covert attention. However, it is not yet clear how such covert shifts of visual attention to peripheral regions impact the processing of the targets we directly foveate as they move in our visual field. The current study utilised the co-registration of eye-position and EEG recordings while participants tracked moving targets that were embedded with a 30 Hz frequency tag in a Steady State Visually Evoked Potentials (SSVEP) paradigm. When the task required attention to be divided between the moving target (overt attention) and a peripheral region where a second target might appear (covert attention), the SSVEPs elicited by the tracked target at the 30 Hz frequency band were significantly lower than when participants did not have to covertly monitor for a second target. Our findings suggest that neural responses of overt attention are reduced when attention is divided between covert and overt areas. This neural evidence is in line with theoretical accounts describing attention as a pool of finite resources, such as the perceptual load theory. Altogether, these results have practical implications for many real-world situations where covert shifts of attention may reduce visual processing of objects even when they are directly being tracked with the eyes.
Realistic fisheries management reforms could mitigate the impacts of climate change in most countries
Authors: Free Christopher M. , Mangin Tracey , Molinos Jorge García , Ojea Elena , Costello Christopher , Gaines Steven D.
Published: October 2019

Although climate change is altering the productivity and distribution of marine fisheries, climate-adaptive fisheries management could mitigate many of the negative impacts on human society. We forecast global fisheries biomass, catch, and profits to 2100 under three climate scenarios (RCPs 4.5, 6.0, 8.5) and five levels of management reform to (1) determine the impact of climate change on national fisheries and (2) quantify the national-scale benefits of implementing climate-adaptive fisheries reforms. Management reforms accounting for shifting productivity and shifting distributions would yield higher catch and profits in the future relative to today for 60-65% of countries under the two least severe climate scenarios but for only 35% of countries under the most severe scenario. Furthermore, these management reforms would yield higher cumulative catch and profits than business-as-usual management for nearly all countries under the two least severe climate scenarios but would yield lower cumulative catch for 40% of countries under the most severe scenario. Fortunately, perfect fisheries management is not necessary to achieve these benefits: transboundary cooperation with 5-year intervals between adaptive interventions would result in comparable outcomes. However, the ability for realistic management reforms to offset the negative impacts of climate change is bounded by changes in underlying biological productivity. Although realistic reforms could generate higher catch and profits for 23-50% of countries experiencing reductions in productivity, the remaining countries would need to develop, expand, and reform aquaculture and other food production sectors to offset losses in capture fisheries. Still, climate-adaptive management is more profitable than business-as-usual management in all countries and we provide guidance on implementing – and achieving the benefits of – climate-adaptive fisheries reform along a gradient of scientific, management, and enforcement capacities.
Frequency Conservation Score (FCS): the power of conservation and allele frequency for variant pathogenic prediction
Authors: Alarcon Jose Luis Cabrera , Enriquez Jose Antonio , Sánchez-Cabo Fátima
Published: October 2019

Background

Prediction of pathogenic variants is one of the biggest challenges for researchers and clinicians in the time of next-generation sequencing technologies. Stratification of individuals based on truly pathogenic variants might lead to improved, personalized treatments.

Results

We present Frequency Conservation Score (FCS) and Frequency Conservation Score for Mitochondrial DNA (FCSMt) two methods for the detection of pathogenic single nucleotide variants in nuclear and mitochondrial DNA, respectively. These scores are based in a random forest model trained over a set of potentially relevant predictors: (i) conservation scores (PhastCons and phyloP); (ii) locus variability at each genomic position built from gnomAD database and (iii) physicochemical distance for amino acids substitutions and the impact/consequence over the canonical transcript. FCS showed an AUC of 98% for deleteriousness in an independent validation dataset, outperforming other scores such as metaLR, metaSVM, REVEL, DANN, CADD, SIFT, PROVEAN or FATHMM-MKL. Moreover, FCSMt presented an AUC=0.92 for pathogenic mitochondrial SNVs detection. The tool is available at http://bioinfo.cnic.es/FCS

Conclusions

FCS and FCS-Mt improve pathogenic mutation detection, allowing the prioritization of relevant variants in Whole Exome and Whole Genome Sequencing Analysis.
Feasibility of spiral fMRI based on an LTI gradient model
Authors: Graedel Nadine N. , Kasper Lars , Engel Maria , Nussbaum Jennifer , Wilm Bertram J. , Pruessmann Klaas P. , Vannesjo S. Johanna
Published: October 2019

Spiral imaging is very well suited for functional MRI, however its use has been limited by the fact that artifacts caused by gradient imperfections and B0 inhomogeneity are more difficult to correct compared to EPI. Effective correction requires accurate knowledge of the traversed k-space trajectory. With the goal of making spiral fMRI more accessible, we have evaluated image reconstruction using trajectories predicted by the gradient impulse response function (GIRF), which can be determined in a one-time calibration step.

GIRF-predicted reconstruction was tested for high-resolution (0.8 mm) fMRI at 7T. Image quality and functional results of the reconstructions using GIRF-prediction were compared to reconstructions using the delay-corrected nominal trajectory and concurrent field monitoring.

The reconstructions using nominal spiral trajectories contain substantial artifacts and the activation maps contain misplaced activation. Image artifacts are substantially reduced when using the GIRF-predicted reconstruction, and the activation maps for the GIRF-predicted and monitored reconstructions largely overlap. The GIRF reconstruction provides a large increase in the spatial specificity of the activation compared to the nominal reconstruction.

The GIRF-reconstruction generates image quality and fMRI results similar to using a concurrently monitored trajectory. The presented approach does not prolong or complicate the fMRI acquisition. Using GIRF-predicted trajectories has the potential to enable high-quality spiral fMRI in situations where concurrent trajectory monitoring is not available.

Highlights

This work investigates the feasibility of using a one-time system calibration to account for k-space trajectory deviations in spiral fMRI.

This versatile calibration is based on a linear time-invariant gradient model, the gradient impulse response function (GIRF).

We show that the image quality and the spatial specificity of the fMRI activation are substantially improved when using the GIRF-predicted trajectories.

Basing reconstructions on nominal gradient inputs, on the other hand, induces image artifacts and misplaced fMRI activation.

We demonstrate that system characterization via the GIRF can enable spiral fMRI in situations where concurrent trajectory monitoring is unavailable.
Mutational signatures of replication timing and epigenetic modification persist through the global divergence of mutation spectra across the great ape phylogeny
Authors: Goldberg Michael E. , Harris Kelley
Published: October 2019

Great ape clades exhibit variation in the relative mutation rates of different three-base-pair genomic motifs, with closely related species having more similar mutation spectra than distantly related species. This pattern cannot be explained by classical demographic or selective forces, but imply that DNA replication fidelity has been perturbed in different ways on each branch of the great ape phylogeny. Here, we use whole-genome variation from 88 great apes to investigate whether these species’ mutation spectra are broadly differentiated across the entire genome, or whether mutation spectrum differences are driven by DNA compartments that have particular functional features or chromatin states. We perform principal component analysis and mutational signature deconvolution on mutation spectra ascertained from compartments defined by features including replication timing and ancient repeat content, finding evidence for consistent species-specific mutational signatures that do not depend on which functional compartments the spectra are ascertained from. At the same time, we find that many compartments have their own characteristic mutational signatures that appear stable across the great ape phylogeny. For example, in a mutation spectrum PCA compartmentalized by replication timing, the second PC explaining 21.2% of variation separates all species’ late-replicating regions from their early-replicating regions. Our results suggest that great ape mutation spectrum evolution is not driven by epigenetic changes that modify mutation rates in specific genomic regions, but instead by trans-acting mutational modifiers that affect mutagenesis across the whole genome fairly uniformly.

SIGNIFICANCE STATEMENT

All heritable variation begins with damage or copying mistakes affecting the DNA of sperm, eggs, or embryos. Different DNA motifs can have different mutation rates, and these rates can evolve over time: the spectrum of mutability of three-base-pair motifs has evolved rapidly during great ape diversification. Here, we show that even as ape mutation spectra diverged from each other, ape genomes preserved a landscape of spatial mutation spectrum variation. We can thus deconvolute the mutational process into a mixture of fast-evolving signatures with uniform spatial distributions and conserved signatures that target specific regions. Our findings may ultimately help determine the factors, either genetic or environmental, that contribute to temporal and spatial variation in germline mutagenesis.
Prediction errors indexed by the P3 track the updating of complex long-term memory schemas
Authors: Richter Franziska R.
Published: October 2019

Memory schemas are higher-level knowledge structures that store an abstraction of multiple previous experiences. They allow us to retain a multitude of information without the cost of storing every detail. Schemas are believed to be relatively stable, but occasionally have to be updated to remain useful in the face of changing environmental conditions. Once a schema is consolidated, schema updating has been proposed to be the result of a prediction-error (PE) based learning mechanism, similar to the updating of less complex knowledge. However, for schema memory this hypothesis has been difficult to test because no sufficiently sensitive tools to track modifications to complex memory schemas existed so far. Current research on the updating of less complex beliefs and at much shorter time scales has identified the P3 as an electrophysiological correlate of PE-induced updating of beliefs. In this study, I recorded electroencephalography and continuous memory measures during the encoding of schema consistent vs. inconsistent material to test the behavioural and neural correlates of schema updating. I observed that PEs predicted the updating of a schema after a 24-hour delay, especially when participants were faced with inconsistent compared to consistent material. Moreover, the P3 amplitude tracked both the PE at the time of learning as well as the updating of the memory schema in the inconsistent condition. These results demonstrate that schema updating in the face of inconsistent information is driven by PE-based learning, and that similar neural mechanisms underlie the updating of consolidated long-term memory schemas and short-term belief structures.
The Rho/Rac guanine nucleotide exchange factor Vav1 regulates HIF-1α and GLUT-1 expression and glucose uptake in the brain
Authors: Hong Jaewoo , Kim Yurim , Yanpallewar Sudhirkumar , Lin P. Charles
Published: October 2019

Vav1 is a Rho/Rac guanine nucleotide exchange factor expressed in hematopoietic and endothelial cells that are involved in a wide range of cellular functions. It is also stabilized under hypoxic conditions when it regulates the accumulation of the transcription factor HIF-1α, which activates the transcription of target genes to orchestrate a cellular response to low oxygen. One of the genes induced by HIF-1α is GLUT-1, which is the major glucose transporter expressed in vessels that supply energy to the brain. Here, we identify a role for Vav1 in providing glucose to the brain. We found that Vav1 deficiency downregulates HIF-1α and GLUT-1 levels in endothelial cells, including blood-brain barrier cells. This downregulation of GLUT-1, in turn, reduced glucose uptake to endothelial cells both in vitro and in vivo, and reduced glucose levels in the brain.

Furthermore, endothelial cell-specific Vav1 knock-out in mice, which caused glucose uptake deficiency, also led to a learning delay in fear conditioning experiments. Our results suggest that Vav1 promotes learning by activating HIF-1α and GLUT-1 and thereby distributing glucose to the brain. They further demonstrate the importance of glucose transport by endothelial cells in brain functioning and reveal a potential new axis for targeting GLUT-1 deficiency syndromes and other related brain diseases.
Quantifying the complexity of subassemblies in a fully automated assembly system
Authors: Gao Yicong , He Chuan , Zheng Bing , Zheng Hao , Tan Jianrong
Published: October 2019

Purpose

Complexity is the main challenge for present and future manufacturers. Assembly complexity heavily affects a product’s final quality in the fully automated assembly system. This paper aims to propose a new method to assess the complexity of modern automated assembly system at the assembly design stage with respect to the characteristics of both manufacturing system and each single component to be mounted. Aiming at validating the predictive model, a regression model is additionally presented to estimate the statistic relationship between the real assembly defect rate and predicted complexity of the fully automated assembly system.

Design/methodology/approach

The research herein extends the S. N. Samy and H. A. ElMaraghy’s model and seeks to redefine the predictive model using fuzzy evaluation against a fully automated assembly process at the assembly design stages. As the evaluation based on the deterministic scale with accurate crisp number can hardly reflect the uncertainty of the judgement, fuzzy linguistic variables are used to measure the interaction among influence factors. A dependency matrix is proposed to estimate the assembly complexity with respect to the interactions between mechanic design, electric design and process factors and main functions of assembly system. Furthermore, a complexity attributes matrix of single part is presented, to map the relationship between all individual parts to be mounted and three major factors mentioned in the dependency matrix.

Findings

The new proposed model presents a formal quantification to predict assembly complexity. It clarifies that how the attributes of assembly system and product components complicate the assembly process and in turn influence the manufacturing performance. A center bolt valve in the camshaft of continue variable valve timing is used to demonstrate the application of the developed methodology in this study.

Originality/value

This paper presents a developed method, which can be used to improve the design solution of assembly concept and optimize the process flow with the least complexity.
Designing, writing-up and reviewing case study research: an equifinality perspective
Authors: Verleye Katrien
Published: October 2019

Purpose

Several researchers struggle with designing, writing-up and reviewing case study research, but constructing a template for describing and justifying methodological choices is – in contrast with quantitative research – undesirable due to the creative nature of qualitative research. Therefore, the purpose of this paper is to provide insight into the multitude of paths to rigorous case study research and promote rigorous case study research in the service community.

Design/methodology/approach

Based upon a review of seminal articles and textbooks, different paths to rigorous case study research are identified. Subsequently, these paths are compared with existing practices in case studies in service research published between March 2017 and April 2019.

Findings

Seminal articles and textbooks detail different paths to achieve rigor with regard to research purpose, design, data, analyses and write-up. Overall, the most popular paths in the service community are those proposed by Eisenhardt and Yin. Meanwhile, service researchers increasingly challenge the dichotomy between the inductive and deductive logic by choosing an abductive logic. Transparency and reflexivity are the main points of attention among service researchers doing case study research.

Originality/value

By providing insight into the multitude of paths to rigorous case study research along with their popularity in the service community, this paper helps service researchers to balance rigor and creativity when engaging in case study research. Additionally, this paper offers a framework for reviewing case study research in terms of rigor and creativity.
Topographic path analysis for modelling dispersal and functional connectivity: Calculating topographic distances using the topoDistance r package
Authors: Wang Ian J.
Published: October 2019

Estimating biologically meaningful geographic distances is essential for research in disciplines ranging from landscape genetics to community ecology. Topographically correcting distances to account for the total overland distance between locations imposed by topographic relief provides one method for calculating geographic distances that account for landscape structure.

Here, I present topoDistance, an r package for calculating shortest topographic distances, weighted topographic paths and topographic least cost paths (LCPs). Topographic distances are calculated by weighting the edges of a graph by the hypotenuse of the horizontal and vertical distances between raster cells and then finding the shortest total path between cells of interest. The package also includes tools for mapping topographic paths and plotting elevation profiles.

Examples from a species with moderate dispersal abilities, the western fence lizard, inhabiting a topographically complex landscape, Yosemite National Park (USA), demonstrate that topographic distances can vary significantly from straight‐line distances, and topographic LCPs can trace very different routes from LCPs and shortest topographic paths.

Topographic paths and distances are broadly useful for modelling geographic isolation resulting from dispersal limitation for organisms that interact with the topographic structure of a landscape during movement and dispersal.
Local anaesthetic delivery regimens for peripheral nerve catheters: a systematic review and network meta‐analysis
Authors: Law W. Z. W. , Sara R. A. , Cameron A. J. D. , Lightfoot N. J.
Published: October 2019

There are numerous possible techniques for delivering local anaesthetic through peripheral nerve catheters. These include continuous infusions, patient‐controlled boluses and programmed intermittent boluses. The optimal delivery regimen of local anaesthetic is yet to be conclusively established. In this review, we identified prospective trials of delivery regimens through peripheral nerve catheters. Our primary outcome was visual analogue scale scores for pain at 48 h. Secondary outcomes were: visual analogue scores at 24 h; patient satisfaction scores; rescue opioid use; local anaesthetic consumption; and nausea and vomiting. Network meta‐analysis was used to compare these outcomes. Predefined sub‐group analyses were performed. Thirty‐three studies enrolling 1934 participants were included. In comparison with continuous infusion, programmed intermittent boluses improved visual analogue pain scores at both 48 and 24 h, the weighted mean difference (95%CI) being −0.63 (−1.12 to −0.14), p = 0.012 and −0.48 (−0.92 to −0.03), p = 0.034, respectively. Programmed intermittent boluses also improved satisfaction scores, the weighted mean difference (95%CI) being 0.70 (0.10–1.31), p = 0.023, and reduced rescue opioid use, the weighted mean difference (95%CI) in oral morphine equivalent at 24 h being −23.84 mg (−43.90 mg to −3.77 mg), p = 0.020. Sub‐group analysis revealed that these findings were mostly confined to lower limb and truncal catheter studies; there were few studies of programmed intermittent boluses for upper limb catheters. Programmed intermittent boluses may provide optimal delivery of a local anaesthetic through peripheral nerve catheters. Further research is warranted, particularly to delineate the differences between upper and lower limb catheter locations, which will help clarify the clinical relevance of these findings.
What are women stressed about after birth?
Authors: Ayers Susan , Crawley Rosalind , Webb Rebecca , Button Susan , Thornton Alexandra ,   the HABiT collaborative group
Published: October 2019

Background

Having a baby is associated with a variety of stressors, change, and adjustment. This study aimed to identify what women find stressful during the early postpartum period in contemporary Western society.

Methods

Women (n = 148) 6‐12 weeks postpartum wrote anonymously about a situation they found stressful as part of the Health after Birth Trial (HABiT) of expressive writing. Transcripts were analyzed for categories of stressors and cross‐cutting themes.

Results

Five categories of stressors were identified. Stressors in pregnancy, labor, and the early postpartum period (49.3%) included physical and emotional difficulties, and insensitive treatment by health professionals. Stressors related to adjusting to life with a baby (35.8%) included difficulties coping with a new baby, parenting, juggling responsibilities, changes to physical health, and loneliness. Stressors related to the baby's health (32.4%) included infant digestive problems, acute health problems, long‐term impact, and neonatal intensive care unit experiences. Stressors related to breastfeeding (23.7%) included pressure to breastfeed, feeling like a ‘bad mum’ for not breastfeeding, or wanting to breastfeed and not being able to. Other stressors related to changing relationships (18.2%): with their partner, children, and other family members. Cross‐cutting themes that emerged in different stressor categories were women making negative self‐appraisals (eg, a bad mum, failure), feeling guilty, and lack of support from others.

Discussion

Our findings emphasize the importance of exploring stressors and psychological well‐being with women to provide support, help women's adjustment postpartum, and ensure interventions are offered when appropriate.
Impacts of competition and herbivory on native plants in a community‐engaged, adaptively managed restoration experiment
Authors: Kimball Sarah , Long Jennifer J. , Ludovise Sara , Ta Priscilla , Schmidt Katharina T. , Halsch Chris A. , Magliano Kaitlin , Huxman Travis , Kang Hosun , Santagata Rossella , Nguyen Lana
Published: October 2019

Restoring biodiversity to degraded sites in the wildland–urban interface is challenging due to many factors, including competition with non‐native species and increased herbivore pressure. In a unique collaboration between land managers, environmental educators, students, and academic ecologists, we tested the effectiveness of multiple restoration techniques in an adaptive management framework, modifying methods each year based on results in the previous years. We evaluated the impact of non‐native species and rabbit herbivores on soil moisture and native plant growth. We added native seedlings to our site either immediately adjacent to existing native shrubs (potential nurse plants) or in the open. One native species, Artemisia californica, was significantly negatively influenced by the presence of an existing shrub and grew more in the open in both a wet and a dry year. Another native species, Eriogonum fasciculatum, experienced high mortality by rabbit herbivores when it was not protected by fencing. Fencing also increased abundance of non‐native plants, so a combination of fencing and non‐native removal without a nurse plant was optimal for restoration. Soil moisture was greater in the open than under existing native shrubs, indicating that existing shrubs decreased soil water available to seedlings. Data collected by trained students was indistinguishable from that collected by professional ecologists. Our use of community‐engaged science demonstrates how scientific adaptive management experiments can include a diversity of participants and allow for immediate dissemination and implementation of results.