bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Influencing the Occurrence of Foliar Pathogens in Commercial Watermelon Fields in South Carolina Based on Stratified Cluster Sampling
Authors: Rennberger Gabriel , Gerard Patrick , Keinath Anthony P.
Published: September 2018

The influence of environmental and management factors on the occurrence of foliar pathogens of watermelon was analyzed using survey-sampling data collected from commercial farms in South Carolina in spring 2015 and spring and fall 2016. A stratified two-stage cluster sampling design was used to sample symptomatic watermelon leaves from 56 fields of 27 growers in seven counties representing the main watermelon-producing areas in the state. In the sampling design, counties corresponded to strata, growers to first-stage clusters, and fields to second-stage clusters. Pathogens were identified on 100 leaves collected per field based on reproductive structures that formed on the leaves. Information about previous crops, fruit type, field size, transplanting date, first harvest date, and fungicides applied within 7 days and within 7 to 14 days prior to sampling was obtained from growers. Field alignment was determined with a compass. Survey-specific logistic regression procedures were used to analyze the effect of these factors on the probabilities of pathogen occurrence. Five fungal pathogens, Stagonosporopsis spp., Podosphaera xanthii, Cercospora citrullina, Colletotrichum orbiculare, and Myrothecium sensu lato (s.l.), and the oomycete Pseudoperonospora cubensis were included in the analyses. Among the factors we analyzed, there was a consistent increased probability of occurrence of Stagonosporopsis spp. in fields with a previous cucurbit crop, increasing probabilities of pathogen occurrence with increasing plant age, a lower probability of occurrence of some pathogens on triploid cultivars compared with diploid cultivars, and a decrease in probability of pathogen occurrence in fields aligned toward southwest or west. Application of fungicides significantly reduced the probability of observing C. citrullina, P. cubensis, and Stagonosporopsis spp. in 2015 and P. xanthii in spring 2016. This study emphasizes the importance of crop rotation and fungicide applications to manage foliar diseases of watermelon, particularly gummy stem blight, powdery mildew, and downy mildew. Crop age, cultivar type, and field alignment also were found to significantly influence the probability of pathogen occurrence. To the best of our knowledge, this is the first study examining the influence of various factors on foliar pathogens of watermelon with data collected from commercial fields.
A Novel Genetic Variant ofGrapevine leafroll-associated virus-3(GLRaV-3) from Idaho Grapevines
Authors: Thompson Brandon D. , Dahan Jennifer , Lee Jungmin , Martin Robert R. , Karasev Alexander V.
Published: September 2018

Grapevine leafroll-associated virus-3 (GLRaV-3) is a major constraint on profitable grapevine cultivation. The virus is transmitted efficiently by mealybugs and soft scale insects, or through vegetative propagation by cuttings, and is present worldwide, wherever grapevines are grown. GLRaV-3 exists as a complex of genetic variants currently classified in several phylogenetic groups that can differ from each other by as much as 30% in nucleotide sequence of the whole genome. In the course of the GLRaV-3 testing of wine grapes in southern Idaho, plants of two grapevine cultivars were found to harbor a novel genetic variant of GLRaV-3, named ID45, which exhibited ≤80% nucleotide sequence identity level to the known GLRaV-3 isolates in its most conserved HSP70h gene. The ID45 variant caused no foliar symptoms in ‘Cabernet Sauvignon’ in the fall, and was demonstrated to have poor reactivity to commercial virus-specific antibodies. The entire 18,478-nt genome sequence of the GLRaV-3-ID45 was determined using a combination of high-throughput and conventional Sanger sequencing, and demonstrated to have typical organization for the genus Ampelovirus (family Closteroviridae), with only 70 to 77% identity level to the GLRaV-3 genomes from other established phylogroups. We concluded that ID45 represented a new phylogenetic group IX of GLRaV-3. Database search using ID45 nucleotide sequence as a query suggested that this novel ID45 variant is present in at least one other grape-growing state in the U.S., California, and in Brazil. An RT-PCR based test was developed to distinguish ID45 from the predominant GLRaV-3 phylogroup I found in Idaho in single and mixed infections.
Cochlear Implantation With a Novel Long Straight Electrode: the Insertion Results Evaluated by Imaging and Histology in Human Temporal Bones
Authors: Sipari Sini , Iso-Mustajärvi Matti , Matikka Hanna , Tervaniemi Jyrki , Koistinen Arto , Aarnisalo Antti , Sinkkonen Saku T. , Löppönen Heikki , Dietz Aarno
Published: September 2018

Hypothesis:

To evaluate the insertion results of a novel straight array (EVO) by detailed imaging and subsequent histology in human temporal bones (TB).

Background:

The main focuses of modern cochlear implant surgery are to prevent damage to the intracochlear structures and to preserve residual hearing. This is often achievable with new atraumatic electrode arrays in combination with meticulous surgical techniques.

Methods:

Twenty fresh-frozen TBs were implanted with the EVO. Pre- and postoperative cone beam computed tomography scans were reconstructed and fused for an artifact-free representation of the electrode. The array's vertical position was quantified in relation to the basilar membrane on basis of which trauma was classified (Grades 0–4). The basilar membrane location was modeled from previous histologic data. The TBs underwent subsequent histologic examination.

Results:

The EVOs were successfully inserted in all TBs. Atraumatic insertion (Grades 0–1) were accomplished in 14 of 20 TBs (70%). There were three apical translocations, and two basal translocations due to electrode bulging. One TB had multiple translocations. The sensitivity and specificity of imaging for detecting insertion trauma (Grades 2–4) was 87.5% and 97.3.0%, respectively.

Conclusion:

Comparable insertion results as reported for other arrays were also found for the EVO. Insertion trauma can be mostly avoided with meticulous insertion techniques to prevent bulging and by limiting the insertion depth angle to 360 degrees. The image fusion technique is a reliable tool for evaluating electrode placement and is feasible for trauma grading.
Is There a Relationship Between Bone Quality and Hearing Level?
Authors: Lee Seung Yeol , Hong Hyung Sun , Yang Seung-Chan , Kim Kyu-Sung , Kim Hyun Ji
Published: September 2018

Objectives:

This study evaluated the correlation between skull bone attenuation on temporal bone computed tomography (CT) and bone mineral density (BMD) of the central skeleton on dual-energy x-ray absorptiometry (DXA) and the correlation between bone quality and hearing level.

Study Design:

Retrospective observational.

Setting:

Tertiary referral center.

Patients/Interventions:

One hundred and one ears of 101 patients who underwent temporal bone CT and DXA with pure tone audiometry within 3 months of CT.

Main Outcome Measures:

Bone quality was measured by both bone attenuation of the clivus and petrous apex by setting a circular region of interest and by the cortical thickness of the occipital bone on CT. Partial correlation analysis was used to assess the correlation between bone quality around the skull on CT and BMD in the central skeleton after adjusting for age and sex. Partial correlations between pure tone audiometry and CT/DXA results were sought.

Results:

There was no significant correlation between measurements on CT and BMD on DXA. The hearing level partially correlated with BMD on DXA. The average threshold of bone conduction showed a significant correlation with BMD at the femoral neck (correlation coefficient −0.241, p = 0.020) and trochanter (correlation coefficient −0.244, p = 0.018), but there was no significant correlation between the average threshold of bone conduction and BMD at the lumbar spine (p = 0.177–0.332).

Conclusion:

We could not find a relationship between hearing loss and bone quality. Hearing levels can be affected by various factors, so further studies are needed to assess regional temporal bone quality.
Unilateral Versus Bilateral Cochlear Implantation in Children With Auditory Neuropathy Spectrum Disorder (ANSD)
Authors: Nassiri Ashley M. , Yawn Robert J. , Brown Christine L. , O’Malley Matthew R. , Bennett Marc L. , Labadie Robert F. , Haynes David S. , Rivas Alejandro
Published: September 2018

Objective:

To evaluate audiologic outcomes following unilateral cochlear implantation with contralateral hearing aid (unilateral CI + HA) versus bilateral CI in children with auditory neuropathy spectrum disorder (ANSD).

Study Design:

Retrospective case review.

Setting:

Tertiary Care Otologic Practice.

Patients:

Twenty-three patients with ANSD who underwent unilateral CI + HA or bilateral CI.

Interventions:

Rehabilitative (CI).

Outcome Measures:

Speech perception scores and achievement of open-set speech.

Results:

Preoperatively, all patients demonstrated lack of open-set speech perception with hearing aids (HAs) alone. Of the 23 patients included, 56.5% (n = 13) had developmental delay. Thirteen patients underwent unilateral CI + HA and 10 patients underwent bilateral CI. The median ages at CI activation were 3.3 and 2.0 years in the unilateral CI + HA and bilateral CI groups, respectively (p = 0.0688), with median lengths of CI use of 45.9 and 47.2 months, respectively (p = 0.8438). The unilateral CI + HA and bilateral CI groups achieved open-set speech perception in 76.9% and 90.0% of cases, respectively (p = 0.6036), within median times of 19.5 and 28.0 months, respectively (p = 0.6334). Within the unilateral CI + HA group, the median aided PTAs in the contralateral ears of patients who did and did not achieve open-set speech were 57.5 dB HL (range, 42.5–91.7 dB HL) and 75.0 dB HL (range, 62.5–111.3 dB HL) (p = 0.0455).

Conclusions:

Both bilateral CI and unilateral CI + HA groups achieved high rates of open-set speech perception. Bilateral CI may be beneficial in patients with bilateral hearing loss or those that fail to progress with unilateral CI + HA.
Connectome to behaviour: modelling
Caenorhabditis elegans
at cellular resolution
Authors: Larson Stephen D. , Gleeson Padraig , Brown André E. X.
Published: September 2018

It has been 30 years since the ‘mind of the worm’ was published in
Philosophical Transactions B
(White
et al
. 1986
Phil. Trans. R. Soc. Lond. B
314
, 1–340). Predicting
Caenorhabditis elegans
' behaviour from its wiring diagram has been an enduring challenge since then. This special theme issue of
Philosophical Transactions B
combines research from neuroscientists, physicists, mathematicians and engineers to discuss advances in neural activity imaging, behaviour quantification and multiscale simulations, and how they are bringing the goal of whole-animal modelling at cellular resolution within reach.

This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling
C. elegans
at cellular resolution’.
Functional connectomics from neural dynamics: probabilistic graphical models for neuronal network ofCaenorhabditis elegans
Authors: Liu Hexuan , Kim Jimin , Shlizerman Eli
Published: September 2018

We propose an approach to represent neuronal network dynamics as a probabilistic graphical model (PGM). To construct the PGM, we collect time series of neuronal responses produced by the neuronal network and use singular value decomposition to obtain a low-dimensional projection of the time-series data. We then extract dominant patterns from the projections to get pairwise dependency information and create a graphical model for the full network. The outcome model is a functional connectome that captures how stimuli propagate through the network and thus represents causal dependencies between neurons and stimuli. We apply our methodology to a model of theCaenorhabditis eleganssomatic nervous system to validate and show an example of our approach. The structure and dynamics of theC. elegansnervous system are well studied and a model that generates neuronal responses is available. The resulting PGM enables us to obtain and verify underlying neuronal pathways for known behavioural scenarios and detect possible pathways for novel scenarios.

This article is part of a discussion meeting issue ‘Connectome to behaviour: modellingC. elegansat cellular resolution’.
An explorable public transcriptomics compendium for eukaryotic microalgae
Authors: Ashworth Justin , Ralph Peter J.
Published: September 2018

Eukaryotic microalgae dominate primary photosynthetic productivity in fluctuating nutrient-rich environments, including coastal, estuarine and polar regions, where competition and complexity are presumably adaptive and dynamic traits. Numerous genomes and transcriptomes of these species have been carefully sequenced, providing an unprecedented view into the vast genetic repertoires and the diverse transcriptional programs operating inside these organisms. Here we collected, re-mapped, quantified and clustered publicly available transcriptome data for ten different eukaryotic microalgae in order to develop new insights into their molecular systems biology, as well as to provide a large new resource of integrated information to facilitate the efforts of others to further compare and contextualize the results of individual and new experiments within and between species. This is summarized herein and provided for public use by the eukaryotic microalgae research community.
Early Pleistocene enamel proteome sequences from Dmanisi resolve Stephanorhinus phylogeny
Authors: Cappellini Enrico , Welker Frido , Pandolfi Luca , Madrigal Jazmin Ramos , Fotakis Anna K. , Lyon David , Moreno Mayar Victor J. , Bukhsianidze Maia , Jersie-Christensen Rosa Rakownikow , Mackie Meaghan , Ginolhac Aurélien , Ferring Reid , Tappen Martha , Palkopoulou Eleftheria , Samodova Diana , Rüther Patrick L. , Dickinson Marc R. , Stafford Tom , Chan Yvonne L. , Götherström Anders , Nathan Senthilvel KSS , Heintzman Peter D. , Kapp Joshua D. , Kirillova Irina , Moodley Yoshan , Agusti Jordi , Kahlke Ralf-Dietrich , Kiladze Gocha , Martínez-Navarro Bienvenido , Liu Shanlin , Velasco Marcela Sandoval , Sinding Mikkel-Holger S. , Kelstrup Christian D. , Allentoft Morten E. , Krogh Anders , Orlando Ludovic , Penkman Kirsty , Shapiro Beth , Rook Lorenzo , Dalén Love , Gilbert M. Thomas P. , Olsen Jesper V. , Lordkipanidze David , Willerslev Eske
Published: September 2018

Ancient DNA (aDNA) sequencing has enabled unprecedented reconstruction of speciation, migration, and admixture events for extinct taxa1. Outside the permafrost, however, irreversible aDNA post-mortem degradation2 has so far limited aDNA recovery within the ˜0.5 million years (Ma) time range3. Tandem mass spectrometry (MS)-based collagen type I (COL1) sequencing provides direct access to older biomolecular information4, though with limited phylogenetic use. In the absence of molecular evidence, the speciation of several Early and Middle Pleistocene extinct species remain contentious. In this study, we address the phylogenetic relationships of the Eurasian Pleistocene Rhinocerotidae5-7 using ˜1.77 million years (Ma) old dental enamel proteome sequences of a Stephanorhinus specimen from the Dmanisi archaeological site in Georgia (South Caucasus)8. Molecular phylogenetic analyses place the Dmanisi Stephanorhinus as a sister group to the woolly (Coelodonta antiquitatis) and Merck’s rhinoceros (S. kirchbergensis) clade. We show that Coelodonta evolved from an early Stephanorhinus lineage and that this genus includes at least two distinct evolutionary lines. As such, the genus Stephanorhinus is currently paraphyletic and its systematic revision is therefore needed. We demonstrate that Early Pleistocene dental enamel proteome sequencing overcomes the limits of ancient collagen- and aDNA-based phylogenetic inference, and also provides additional information about the sex and taxonomic assignment of the specimens analysed. Dental enamel, the hardest tissue in vertebrates, is highly abundant in the fossil record. Our findings reveal that palaeoproteomic investigation of this material can push biomolecular investigation further back into the Early Pleistocene.
Towards a “Treadmill Test” for Cognition: Reliable Prediction of Intelligence From Whole-Brain Task Activation Patterns
Authors: Sripada Chandra , Angstadt Mike , Rutherford Saige
Published: September 2018

Identifying brain-based markers of general cognitive ability, i.e., “intelligence”, has been a longstanding goal of cognitive and clinical neuroscience. Previous studies focused on relatively static, enduring features such as gray matter volume and white matter structure. In this report, we investigate prediction of intelligence based on task activation patterns during theN-back working memory task as well as six other tasks in the Human Connectome Project dataset, encompassing 19 task contrasts. We find that whole brain task activation patterns are a highly effective basis for prediction of intelligence, achieving a 0.68 correlation with intelligence scores in an independent sample, which exceeds results reported from other modalities. Additionally, we show that tasks that tap executive processing and that are more cognitively demanding are particularly effective for intelligence prediction. These results suggest a picture analogous to treadmill testing for cardiac function: Placing the brain in an activated task state improves brain-based prediction of intelligence.
Natural selection of glycoprotein B (gB) mutations that rescue the small plaque phenotype of a fusion-impaired herpes simplex virus (HSV) mutant
Authors: Fan Qing , Kopp Sarah J. , Byskosh Nina C. , Connolly Sarah A. , Longnecker Richard
Published: September 2018

Glycoprotein B (gB) is a conserved viral fusion protein that is required for herpesvirus entry. To mediate fusion with the cellular membrane, gB refolds from a prefusion to a postfusion conformation. We hypothesize that an interaction between the C-terminal arm and the central coiled-coil of the herpes simplex virus 1 (HSV-1) gB ectodomain is critical for fusion. We previously reported that three mutations in the C-terminal arm (I671A/H681A/F683A, called gB3A) greatly reduced cell-cell fusion and that virus carrying these mutations had a small plaque phenotype and delayed entry into cells. By serially passaging gB3A virus, we selected three revertant viruses with larger plaques. These revertant viruses acquired mutations in gB that restore the fusion function of gB3A, including gB-A683V, gB-S383F/G645R/V705I/A855V, and gB-T509M/N709H. V705I and N709H are novel mutations that map to the portion of domain V that enters domain I in the postfusion structure. S383F, G645R, and T509M are novel mutations that map to an intersection of three domains in a prefusion model of gB. We introduced these second-site mutations individually and in combination into wild-type gB and gB3A to examine the impact of the mutations on fusion and expression. V705I and A855V (a known hyperfusogenic mutation) restored the fusion function of gB3A, whereas S383F and G645R dampened fusion and T509M and N709H worked in concert to restore gB3A fusion. The results identify two regions in the gB ectodomain that modulate the fusion activity of gB, potentially by impacting intramolecular interactions and stability of the prefusion and/or postfusion gB trimer.

IMPORTANCE

Glycoprotein B (gB) is an essential viral protein that is conserved in all herpesviruses and is required for virus entry. gB is thought to undergo a conformational change that provides the energy to fuse the viral and cellular membranes, however the details of this conformational change and the structure of the prefusion and intermediate conformations of gB are not known. Previously, we demonstrated that mutations in the gB “arm” region inhibit fusion and impart a small plaque phenotype. Using serial passage of a virus carrying these mutations, we identified revertants with restored plaque size. The revertant viruses acquired novel mutations in gB that restored fusion function and mapped to two sites in the gB ectodomain. This work supports our hypothesis that an interaction between the gB arm and the core of gB is critical for gB refolding and provides details about the function of gB in herpesvirus mediated fusion and subsequent virus entry.
The Helicobacter pylori biofilm involves a multi-gene stress-biased response including a structural role for flagella
Authors: Hathroubi Skander , Zerebinski Julia , Ottemann Karen M.
Published: September 2018

Helicobacter pylori has an impressive ability to persist chronically in the human stomach. Similar characteristics are associated with biofilm formation in other bacteria. The H. pylori biofilm process, however, is poorly understood. To gain insight into this mode of growth, we carried out comparative transcriptomic analysis between H. pylori biofilm and planktonic cells, using the mouse colonizing strain SS1. Optimal biofilm formation was obtained with low serum and three-day growth, conditions which caused both biofilm and planktonic cells to be ∼80% coccoid. RNA-seq analysis found that 8.18% of genes were differentially expressed between biofilm and planktonic cell transcriptomes. Biofilm-downregulated genes included those involved in metabolism and translation, suggesting these cells have low metabolic activity. Biofilm-upregulated genes included those whose products were predicted to be at the cell envelope, involved in regulating a stress response, and surprisingly, genes related to formation of the flagellar apparatus. Scanning electron microscopy visualized flagella that appeared to be a component of the biofilm matrix, supported by the observation that an aflagellated mutant displayed a less robust biofilm with no apparent filaments. We observed flagella in the biofilm matrix of additional H. pylori strains, supporting that flagellar use is widespread. Our data thus supports a model in which H. pylori biofilm involves a multi-gene stress-biased response, and that flagella play an important role in H. pylori biofilm formation.

IMPORTANCE

Biofilms, communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances, pose a substantial health risk and are key contributors to many chronic and recurrent infections. Chronicity and recalcitrant infections are also common features associated with the ulcer-causing human pathogen H. pylori. However, relatively little is known about the role of biofilms in H. pylori pathogenesis as well as the biofilm structure itself and the genes associated with this mode of growth. In the present study, we found that H. pylori biofilm cells highly expressed genes related to cell envelope, stress response and those encoding the flagellar apparatus. Flagellar filaments were seen in high abundance in the biofilm. Flagella are known to play a role in initial biofilm formation, but typically are downregulated after that state. H. pylori instead appears to have co-opted these structures for non-motility roles, including a role building a robust biofilm.
Multivariate Computational Analysis of Gamma Delta T cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging
Authors: Belkina Anna C. , Starchenko Alina , Drake Katherine A. , Proctor Elizabeth A. , Pihl Riley M.F. , Olson Alex , Lauffenburger Douglas A. , Lin Nina , Snyder-Cappione Jennifer E.
Published: September 2018

Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age (≤35 or ≥50 years old). For data analysis, multiple multivariate computational algorithms (cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)) were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta (γδ) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from γδ T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ γδ T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of γδ T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate γδ T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct ‘inflamm-aging’ processes with and without ART-suppressed HIV infection.
The emergence of dynamical instantaneous memory in the spontaneous activity of spatially confined neuronal assemblies in vitro
Authors: Piasetzky Y. , Bisio M. , Kanner S. , Goldin M , Olivenbaum M. , Ben-Jacob E. , Hanein Y , Chiappalone M. , Barzilai A. , Bonifazi P.
Published: September 2018

Understanding the dynamics between communicating cell assemblies is essential for deciphering the neural code and identifying the mechanism underlying memory formation. In this work, in order to unveil possible emergent intrinsic memory phenomena in the communication between cell assemblies, we study the spontaneous dynamics of in vitro spatially confined inter-connected neuronal circuits grown on multi-electrode arrays. The spontaneous dynamics of the global network was characterized by the coupling of the activity independently generated by each circuit. The asymptotic functional connectivity of the network reflected its modular organization. Instantaneous functional connectivity maps on ten seconds epochs, revealed more complex dynamical states with the simultaneous activation of distinct circuits. When looking at the similarity of the generated network events, we observed that spontaneous network events occurring at temporal distances below two dozens of seconds had an average higher similarity compared to randomly played network events. Such a memory phenomenon was not observed in networks where spontaneous events were less frequent and in networks topologically organized as open lines. These results support the hypothesis that dynamical instantaneous memory, characterized by drifting network dynamics with decaying degree of similarity, is an intrinsic property of neuronal networks.
Pan-genome-scale network reconstruction: a framework to increase the quantity and quality of metabolic network reconstructions throughout the tree of life
Authors: Correia Kevin , Mahadevan Radhakrishnan
Published: September 2018

A genome-scale network reconstruction (GENRE) represents the knowledgebase of an organism and can be used in a variety of applications. The drop in genome sequencing costs has led to an increase in sequenced genomes, but the number of curated GENRE’ s has not kept pace. This gap hinders our ability to study physiology across the tree of life. Furthermore, our analysis of yeast GENRE’ s has found they contain significant commission and omission errors, especially in central metabolism. To address these quantity and quality issues for GENRE’ s, we propose open and transparent curation of the pan-genome, pan-reactome, pan-metabolome, and pan-phenome for taxons by research communities, rather than for a single species. We outline our approach with a Fungi pan-GENRE by integrating AYbRAH, our ortholog database, and AYbRAHAM, our new fungal reaction database. This pan-GENRE was used to compile 33 yeast/fungi GENRE’ s in the Dikarya subkingdom, spanning 600 million years. The fungal pan-GENRE contains 1547 orthologs, 2726 reactions, 2226 metabolites, and 10 compartments. The strain GENRE’ s have a wider genomic and metabolic than previous yeast and fungi GENRE’ s. Metabolic simulations show the amino acid yields from glucose differs between yeast lineages, indicating metabolic networks have evolved in yeasts. Curating ortholog and reaction databases for a taxon can be used to increase the quantity and quality of strain GENRE’ s. This pan-GENRE framework provides the ability to scale high-quality GENRE’ s to more branches in the tree of life.
Drift-diffusion explains response variability and capacity for tracking objects
Authors: Daneshi Asieh , Azarnoush Hamed , Towhidkhah Farzad , Ghazizadeh Ali
Published: September 2018

1.

Being able to track objects that surround us is key for planning actions in dynamic environments. However, rigorous cognitive models for tracking of one or more objects are currently lacking. In this study, we asked human subjects to judge the time to contact (TTC) a finish line for one or two objects that became invisible shortly after moving. We showed that the pattern of subject responses had an error variance best explained by an inverse Gaussian distribution and consistent with the output of a biased drift-diffusion model. Furthermore, we demonstrated that the pattern of errors made when tracking two objects showed a level of dependence that was consistent with subjects using a single decision variable for reporting the TTC for two objects. This finding reveals a serious limitation in the capacity for tracking multiple objects resulting in error propagation between objects. Apart from explaining our own data, our approach helps interpret previous findings such as asymmetric interference when tracking multiple objects.
Emergence of social inequality in a spatial-ecological public goods game
Authors: Joshi Jaideep , Brännström Åke , Dieckmann Ulf
Published: September 2018

Spatial ecological public goods, such as forests, grasslands, and fish stocks risk being overexploited by selfish consumers, a phenomenon called “the tragedy of commons”. The spatial and ecological dimensions introduce new features absent in non spatio-ecological contexts, such as consumer mobility, incomplete information availability, and rapid evolution by social learning. It is unclear how these different processes interact to influence the harvesting and dispersal strategies of consumers. To answer these questions, we develop and analyze an individual-based, spatially-structured evolutionary model with explicit resource dynamics. We find that, 1) When harvesting efficiency is low, consumers evolve a sedentary harvesting strategy, with which resources are harvested sustainably, but harvesting rates remain far below their maximum sustainable value. 2) As harvesting efficiency increases, consumers adopt a mobile ‘consume-and-disperse’ strategy, which is sustainable, equitable, and allows for maximum sustainable yield. 3) Further increase in harvesting efficiency leads to large-scale overexploitation. 4) If costs of dispersal are significant, increased harvesting efficiency also leads to social inequality between frugal sedentary consumers and overexploitative mobile consumers. Whereas overexploitation can occur without social inequality, social inequality always leads to overexploitation. Thus, we identify four conditions, which are characteristic (and as such positive) features of modern societies resulting from technological progress, but also risk promoting social inequality and unsustainable resource use: high harvesting efficiency, moderately low costs of dispersal, high consumer density, and consumers’ tendency to rapidly adopt new strategies. We also show that access to global information, which is also a feature of modern societies, may help mitigate these risks.
Projection layers improve deep learning models of regulatory DNA function
Authors: Hawkins-Hooker Alex , Kenlay Henry , Reid John
Published: September 2018

With the increasing application of deep learning methods to the modelling of regulatory DNA sequences has come an interest in exploring what types of architecture are best suited to the domain. Networks designed to predict many functional characteristics of noncoding DNA in a multitask framework have to recognise a large number of motifs and as a result benefit from large numbers of convolutional filters in the first layer. The use of large first layers in turn motivates an exploration of strategies for addressing the sparsity of output and possibility for overfitting that result. To this end we propose the use of a dimensionality-reducing linear projection layer after the initial motif-recognising convolutions. In experiments with a reduced version of the DeepSEA dataset we find that inserting this layer in combination with dropout into convolutional and convolutional-recurrent architectures can improve predictive performance across a range of first layer sizes. We further validate our approach by incorporating the projection layer into a new convolutional-recurrent architecture which achieves state of the art performance on the full DeepSEA dataset. Analysis of the learned projection weights shows that the inclusion of this layer simplifies the network’s internal representation of the occurrence of motifs, notably by projecting features representing forward and reverse-complement motifs to similar positions in the lower dimensional feature space output by the layer.
Agrobacterium tumefaciensdivisome proteins regulate the transition from polar growth to cell division
Authors: Howell Matthew , Aliashkevich Alena , Sundararajan Kousik , Daniel Jeremy J. , Lariviere Patrick J. , Goley Erin D. , Cava Felipe , Brown Pamela J.B.
Published: September 2018

The mechanisms that restrict peptidoglycan biosynthesis to the pole during elongation and re-direct peptidoglycan biosynthesis to mid-cell during cell division in polar-growing Alphaproteobacteria are largely unknown. Here, we demonstrate that although two of the three FtsZ homologs localize to mid-cell, exhibit GTPase activity and form co-polymers, only one, FtsZAT, is required for cell division. We find that FtsZATis required not only for constriction and cell separation, but also for the termination of polar growth and regulation of peptidoglycan synthesis at mid-cell. Depletion of FtsZ inA. tumefacienscauses a striking phenotype: cells are extensively branched and accumulate growth active poles through tip splitting events. When cell division is blocked at a later stage, polar growth is terminated and ectopic growth poles emerge from mid-cell. Overall, this work suggests thatA. tumefaciensFtsZ makes distinct contributions to the regulation of polar growth and cell division.
Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies
Authors: Gileta Alexander F. , Fitzpatrick Christopher J. , Chitre Apurva S. , St. Pierre Celine L. , Joyce Elizabeth V. , Maguire Rachael J. , McLeod Africa M. , Gonzales Natalia M. , Williams April E. , Morrow Jonathan D. , Robinson Terry E. , Flagel Shelly B. , Palmer Abraham A.
Published: September 2018

Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies.

Author Summary

Outbred Sprague Dawley rats are among the most commonly used rats for neuroscience, physiology and pharmacological research; in the year 2020, 4,188 publications contained the keyword “Sprague Dawley”. Rats identified as “Sprague Dawley” are sold by several commercial vendors, including Charles River Laboratories and Harlan Sprague Dawley Inc. (now Envigo). Despite their widespread use, little is known about the genetic diversity of SD. We genotyped more than 4,000 SD rats, which we used for a genome-wide association study (GWAS) and to characterize genetic differences between SD rats from Charles River Laboratories and Harlan. Our analysis revealed extensive population structure both between and within vendors. The GWAS for Pavlovian conditioned approach (PavCA) identified a number of genome-wide significant loci for that complex behavioral trait. Our results demonstrate that, despite sharing an identical name, SD rats that are obtained from different vendors are very different. Future studies should carefully define the exact source of SD rats being used and may exploit their genetic diversity for genetic studies of complex traits.
Predominance ofcis-regulatory changes in parallel expression divergence of sticklebacks
Authors: Verta Jukka-Pekka , Jones Felicity C.
Published: September 2018

Regulation of gene expression is thought to play a major role in adaptation but the relative importance ofcis- andtrans-regulatory mechanisms in the early stages of adaptive divergence is unclear. Using RNAseq of threespine stickleback fish gill tissue from four independent marine-freshwater ecotype pairs and their F1 hybrids, we show thatcis-acting (allele-specific) regulation consistently predominates gene expression divergence. Genes showing parallel marine-freshwater expression divergence are found near to adaptive genomic regions, show signatures of natural selection around their transcription start sites and are enriched forcis-regulatory control. For genes with parallel increased expression among freshwater fish, the quantitative degree ofcis-andtrans-regulation is also highly correlated across populations, suggesting a shared genetic basis. Compared to other forms of regulation,cis-regulation tends to show greater additivity and stability across different genetic and environmental contexts, making it a fertile substrate for the early stages of adaptive evolution.
Vitamin A supplement after neonatalStreptococcus pneumoniaepneumonia alters CD4+T cell subset and inhibits allergic asthma in mice model
Authors: Tian Yonglu , Tian Qinqin , Wu Yi , Peng Xin , Chen Yunxiu , Li Qinyuan , Zhang Guangli , Tian Xiaoyin , Ren Luo , Luo Zhengxiu
Published: September 2018

Background

Previously, we showed that neonatal pneumonia caused byStreptococcus pneumoniae(S. pneumoniae) promoted adulthood ovalbumin (OVA) induced allergic asthma. Many studies have demonstrated that vitamin A deficiency induced the development of allergic asthma. Whether neonatalS. pneumoniaepneumonia promoted allergic asthma development was associated with vitamin A concentrations remains unclear.

Methods

Female BALB/c neonates were infected withS. pneumoniaestrain D39 and subsequently treated with vitamin A. Vitamin A concentrations in lung, serum and liver were monitored on 2, 5, 7, 14, 21, 28 days post infection. Four weeks after infection, mice were sensitized and challenged with OVA to induce allergic airway disease (AAD) in early adulthood. Twenty-four hours after the final challenge, lung histo-pathology, cytokine concentrations in bronchoalveolar lavage fluid (BALF), airway hyperresponsiveness (AHR) and lung CD4+T cells were measured.

Results

We demonstrated that neonatalS. pneumoniaepneumonia induce lung vitamin A deficiency up to early adulthood. Moreover, neonatalS. pneumoniaepneumonia aggravated airway inflammatory cells accumulation and increased AHR during AAD, decreased Foxp3+Treg and Th1 productions remarkably, while Th2 cell expression was increased significantly. Further study indicated that vitamin A supplement after neonatalS. pneumoniaepneumonia can promote Foxp3+Treg and Th1 productions, decrease Th2 cell expressions, alleviate AHR and inflammatory cells infiltration during AAD.

Conclusions

Using a mouse model, we demonstrate that Vitamin A supplement after neonatal Streptococcus pneumoniae pneumonia alters the CD4+T cell subset and inhibits the development of early adulthood allergic asthma.
Critical role of miR-10b in BRafV600E dependent anchorage-independent growth and invasion of melanoma cells
Authors: Datar Ila , Kalpana Gardiyawasam , de la Serna Ivana , Trumbly Robert , Choi Jungmin , Yeung Kam C.
Published: September 2018

Recent high-throughput-sequencing of cancer genomes has identified oncogenic mutations in the BRaf genetic locus as one of the critical events in melanomagenesis. BRaf encodes a serine/threonine kinase that regulates the MAPK/ERK kinase (MEK) and extracellular signal-regulated kinase (ERK) protein kinase cascade. In normal cells, the activity of BRaf is tightly regulated and is required for cell growth and survival. BRaf gain-of-function mutations in melanoma frequently lead to unrestrained growth, enhanced cell invasion and increased viability of cancer cells. Although it is clear that the invasive phenotypes of BRaf mutated melanoma cells are stringently dependent on BRaf-MEK-ERK activation, the downstream effector targets that are required for oncogenic BRaf-mediated melanomagenesis are not well defined. miRNAs have regulatory functions towards the expression of genes that are important in carcinogenesis. We observed that miR-10b expression correlates with the presence of the oncogenic BRaf (BRafV600E) mutation in melanoma cells. While expression of miR-10b enhances anchorage-independent growth of BRaf wild-type melanoma cells, miR-10b silencing decreases BRafV600E cancer cell invasion in vitro. Importantly, the expression of miR-10b is required for BRafV600E-mediated anchorage-independent growth and invasion of melanoma cells in vitro. Taken together our results suggest that miR-10b is an important mediator of oncogenic BRafV600E activity in melanoma.
Formation of the substantia nigra requires Reelin-mediated fast, laterally-directed migration of dopaminergic neurons
Authors: Vaswani Ankita Ravi , Weykopf Beatrice , Hagemann Cathleen , Fried Hans-Ulrich , Brüstle Oliver , Blaess Sandra
Published: September 2018

Midbrain dopaminergic (mDA) neurons migrate to form the laterally-located substantia nigra pars compacta (SN) and medially-located ventral tegmental area (VTA), but little is known about the underlying cellular and molecular processes. Reelin signaling regulates tangential migration of SN-mDA neurons, but whether Reelin acts directly on SN-mDA neurons and how it affects their cellular morphology and migratory behavior has not been explored. Here we visualize the dynamic cell morphologies of tangentially migrating SN-mDA neurons with 3D-time-lapse imaging and identify two distinct migration modes. Slow migration is the default mode in SN-mDA neurons, while fast, laterally-directed migration occurs infrequently and is strongly associated with bipolar cell morphology. By speci1cally inactivating Reelin signaling in mDA neurons we demonstrate its direct role in SN-mDA tangential migration. We show that Reelin signaling promotes laterally-biased movements in mDA neurons during their slow migration mode, stabilizes leading process morphology and increases the probability of fast, laterally-directed migration.
Model-free classification of X-ray scattering signals applied to image segmentation
Authors: Lutz-Bueno V. , Arboleda C. , Leu L. , Blunt M. J. , Busch A. , Georgiadis A. , Bertier P. , Schmatz J. , Varga Z. , Villanueva-Perez P. , Wang Z. , Lebugle M. , David C. , Stampanoni M. , Diaz A. , Guizar-Sicairos M. , Menzel A.
Published: September 2018

In most cases, the analysis of small-angle and wide-angle X-ray scattering (SAXS and WAXS, respectively) requires a theoretical model to describe the sample's scattering, complicating the interpretation of the scattering resulting from complex heterogeneous samples. This is the reason why, in general, the analysis of a large number of scattering patterns, such as are generated by time-resolved and scanning methods, remains challenging. Here, a model-free classification method to separate SAXS/WAXS signals on the basis of their inflection points is introduced and demonstrated. This article focuses on the segmentation of scanning SAXS/WAXS maps for which each pixel corresponds to an azimuthally integrated scattering curve. In such a way, the sample composition distribution can be segmented through signal classification without applying a model or previous sample knowledge. Dimensionality reduction and clustering algorithms are employed to classify SAXS/WAXS signals according to their similarity. The number of clusters, i.e. the main sample regions detected by SAXS/WAXS signal similarity, is automatically estimated. From each cluster, a main representative SAXS/WAXS signal is extracted to uncover the spatial distribution of the mixtures of phases that form the sample. As examples of applications, a mudrock sample and two breast tissue lesions are segmented.