bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Mortality Prediction by Quick Sequential Organ Failure Assessment with Emergency Physician Judgment
Authors: Cleek William R. , Johnson Nicholas J. , Watsjold Bjorn K. , Hall Michael Kennedy , Henning Daniel J.
Published: December 2019

Study Objective:

The quick sequential organ failure assessment (qSOFA) was proposed to identify infected patients at risk for mortality, an indication of sepsis, in nonintensive care unit settings. This study tests whether qSOFA improves physician prediction of mortality among infected Emergency Department (ED) patients.

Methods:

We performed a secondary analysis of a prospective, observational study of potentially septic ED patients, conducted between two urban, academic medical centers, from July 2016 to December 2017. We enrolled ED patients with two or more systemic inflammatory response syndrome criteria and severe sepsis qualifying organ dysfunction, systolic blood pressure <90 mm Hg, or lactate ≥ 4.0 mmol/L. Infectious etiology was adjudicated retrospectively by paired physician review. We excluded noninfected patients. Treating ED physicians submitted judgment for in-hospital mortality (0%–100%) at hospital admission, and qSOFA was calculated retrospectively using ED data. The primary outcome was in-hospital mortality within 28 days. We used logistic regression to predict mortality using physician judgment, qSOFA, and combined physician judgment and qSOFA. To assess differences between models, 95% confidence intervals for area under the curve (AUC) were derived by bootstrapping with 1,000 iterations.

Results:

Of 405 patients meeting inclusion criteria, 195 (48.1%) were determined to have infection and analyzed. Of analyzed patients, 16 (8.2%) suffered in-hospital mortality within 28 days. Analyzed patients had a mean age of 58.3 (SD 16.5) years and 78 (40%) were female. qSOFA alone (AUC 0.63; 95% CI: 0.53–0.73) was not superior to unstructured physician judgment (AUC 0.80; 0.70–0.89) when predicting 28-day in-hospital mortality with mean AUC difference 0.17 (0.07–0.28) across bootstrapped datasets. Combining qSOFA with physician judgment (AUC 0.79; 0.69–0.89) did not improve performance compared with physician judgment alone.

Conclusion:

When predicting 28-day in-hospital mortality among infected ED patients, qSOFA did not outperform or improve physician judgment.
Feasibility and Clinical Outcome of Reboa in Patients with Impending Traumatic Cardiac Arrest
Authors: McGreevy David Thomas , Abu-Zidan Fikri M. , Sadeghi Mitra , Pirouzram Artai , Toivola Asko , Skoog Per , Idoguchi Koji , Kon Yuri , Ishida Tokiya , Matsumura Yosuke , Matsumoto Junichi , Reva Viktor , Maszkowski Mariusz , Bersztel Adam , Caragounis Eva-Corina , Falkenberg Mårten , Handolin Lauri , Oosthuizen George , Szarka Endre , Manchev Vassil , Wannatoop Tongporn , Chang Sung Wook , Kessel Boris , Hebron Dan , Shaked Gad , Bala Miklosh , Coccolini Federico , Ansaloni Luca , Ordoñez Carlos A. , Dogan Emanuel M. , Manning James E. , Hibert-Carius Peter , Larzon Thomas , Nilsson Kristofer F. , Hörer Tal Martin
Published: December 2019

Background:

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may improve Systolic Blood Pressure (SBP) in hypovolemic shock. It has, however, not been studied in patients with impending traumatic cardiac arrest (ITCA). We aimed to study the feasibility and clinical outcome of REBOA in patients with ITCA using data from the ABOTrauma Registry.

Methods:

Retrospective and prospective data on the use of REBOA from 16 centers globally were collected. SBP was measured both at pre- and post-REBOA inflation. Data collected included patients’ demography, vascular access technique, number of attempts, catheter size, operator, zone and duration of occlusion, and clinical outcome.

Results:

There were 74 patients in this high-risk patient group. REBOA was performed on all patients. A 7-10Fr catheter was used in 66.7% and 58.5% were placed on the first attempt, 52.1% through blind insertion and 93.2% inflated in Zone I, 64.8% for a period of 30 to 60 min, 82.1% by ER doctors, trauma surgeons, or vascular surgeons. SBP significantly improved to 90 mm Hg following the inflation of REBOA. 36.6% of the patients survived.

Conclusions:

Our study has shown that REBOA may be performed in patients with ITCA, SBP can be elevated, and 36.6% of the patients survived if REBOA placement is successful.
William James Stirling CBE. 4 February 1953—9 November 2018
Authors: Martin A. D. , Webber B. R.
Published: December 2019

James Stirling's wide-ranging contributions to the development and application of quantum chromodynamics were central in verifying QCD as the correct theory of strong interactions, and in computing precise predictions for all types of collider processes. He published more than 300 papers on a vast range of phenomenological topics, including some of the most highly cited of all time in particle physics. His research, always full of insight, focused on the confrontation of theoretical predictions with experimental results. Amongst many key contributions, he developed the helicity amplitude method and used it to show that the CERN ‘monojet’ events, thought to be a possible signal of new physics, were due to vector boson plus jet production. The method has since facilitated the calculation of many other important processes. At Durham he formed a famous long-standing collaboration that set the standard for determining the quark and gluon distributions in the proton. Besides his intellectual brilliance, his personal qualities of humility, modesty, diligence and fairness made him an outstanding scientific leader and administrator. He played a major role in the foundation of the Institute for Particle Physics Phenomenology in Durham and served as its first Director. In 2005 he was appointed Pro-Vice Chancellor for Research at Durham. He moved to the Cavendish Laboratory in Cambridge in 2008, becoming Head of the Department of Physics in 2011. Then in 2013 he was appointed to the newly created position of Provost, the chief academic officer, at Imperial College, London, from which he retired in August 2018.
Research practices and statistical reporting quality in 250 economic psychology master's theses: a meta-research investigation
Authors: Olsen Jerome , Mosen Johanna , Voracek Martin , Kirchler Erich
Published: December 2019

The replicability of research findings has recently been disputed across multiple scientific disciplines. In constructive reaction, the research culture in psychology is facing fundamental changes, but investigations of research practices that led to these improvements have almost exclusively focused on academic researchers. By contrast, we investigated the statistical reporting quality and selected indicators of questionable research practices (QRPs) in psychology students' master's theses. In a total of 250 theses, we investigated utilization and magnitude of standardized effect sizes, along with statistical power, the consistency and completeness of reported results, and possible indications of
p
-hacking and further testing. Effect sizes were reported for 36% of focal tests (median
r
= 0.19), and only a single formal power analysis was reported for sample size determination (median observed power 1 −
β
= 0.67).
Statcheck
revealed inconsistent
p
-values in 18% of cases, while 2% led to decision errors. There were no clear indications of
p
-hacking or further testing. We discuss our findings in the light of promoting open science standards in teaching and student supervision.
Integrating phylogeography and high-resolution X-ray CT reveals five new cryptic species and multiple hybrid zones among Australian earless dragons
Authors: Melville Jane , Chaplin Kirilee , Hipsley Christy A. , Sarre Stephen D. , Sumner Joanna , Hutchinson Mark
Published: December 2019

Cryptic lineages, comprising species complexes with deep genetic structuring across the landscape but without distinct morphological differences, impose substantial difficulties for systematists and taxonomists in determining true species diversity. Here, we present an integrative approach that combines data from phylogeography and geometric morphometric analyses of three-dimensional cranial models to revisit the uncertain taxonomy of earless dragons from southern and central Australia that at one time or another have been included under the name
Tympanocryptis lineata
. Our approach finds strong support for seven previously described species, and more importantly, five undescribed
Tympanocryptis
taxa for which we provide a taxonomic treatment. We also find evidence of introgression and hybridization in three discrete contact zones between lineages, supported by mitochondrial and nuclear genes, as well as morphological analyses. With a sampling design that includes at least five individuals for each genetic lineage with corresponding X-ray microcomputed tomography scans, we perform comparative evolutionary analyses to show that there is a significant phylogenetic signal in
Tympanocryptis
cranial shape. Our results demonstrate the importance of using multiple specimens in each genetic lineage, particularly in cases of potential hybridization, and that geometric morphometrics, when used in an integrative framework, is a powerful tool in species delimitation across cryptic lineages. Our results lay the groundwork for future evolutionary studies in this widespread group across multiple environmental types and identify several species of immediate conservation concern with a focus on
T. petersi
sp. nov. We suggest that this species has undergone significant population declines and warrants a full conservation assessment.
Mass estimation of extinct taxa and phylogenetic hypotheses both influence analyses of character evolution in a large clade of birds (Telluraves)
Authors: Crouch Nicholas M. A. , Mason-Gamer Roberta
Published: December 2019

Incorporating extinct taxa in phylogenetic comparative methods is rapidly becoming invaluable in studies of character evolution. An increasing number of studies have evaluated the effects of extinct taxa, and different numbers of extinct taxa, on model selection and parameter estimation. Body mass is a well-studied phenotype, but individual mass estimates may vary dramatically depending on the particular measurement used. Here, we perform an analysis of body mass evolution in a large clade of principally arboreal birds, incorporating 76 extinct species. We evaluate how different methods for estimating body mass of extinct taxa, and different phylogenetic hypotheses, affect our understanding of the rate and pattern of body mass evolution. Our results show that model selection can vary dramatically depending on the phenotypic and phylogenetic hypothesis used in the reconstruction. Even small changes in phenotype estimates can lead to different model selection and, as a result, affect the inferred evolutionary history. The best-fit models support an increase in the rate of evolution following the K–Pg boundary, with variation accumulating linearly through the Cenozoic. These results provide additional insight into the application of comparative models of evolution, as well as the evolutionary history of one of the most spectacular vertebrate radiations.
Intergroup aggression in meerkats
Authors: Dyble Mark , Houslay Thomas M. , Manser Marta B. , Clutton-Brock Tim
Published: December 2019

Violent conflicts between groups have been observed among many species of group living mammals and can have important fitness consequences, with individuals being injured or killed and with losing groups surrendering territory. Here, we explore between-group conflict among meerkats (Suricata suricatta), a highly social and cooperatively breeding mongoose. We show that interactions between meerkat groups are frequently aggressive and sometimes escalate to fighting and lethal violence and that these interactions have consequences for group territories, with losing groups moving to sleeping burrows closer to the centre of their territories following an intergroup interaction and with winning groups moving further away. We find that larger groups and groups with pups are significantly more likely to win contests, but that the location of the contest, adult sex ratio, and mean within-group genetic relatedness do not predict contest outcome. Our results suggest that intergroup competition may be a major selective force among meerkats, reinforcing the success of large groups and increasing the vulnerability of small groups to extinction. The presence of both within-group cooperation and between-group hostility in meerkats make them a valuable point of comparison in attempts to understand the ecological and evolutionary roots of human warfare.
Pathogen defence is a potential driver of social evolution in ambrosia beetles
Authors: Nuotclà Jon A. , Biedermann Peter H. W. , Taborsky Michael
Published: December 2019

Social immunity—the collective behavioural defences against pathogens—is considered a crucial evolutionary force for the maintenance of insect societies. It has been described and investigated primarily in eusocial insects, but its role in the evolutionary trajectory from parental care to eusociality is little understood. Here, we report on the existence, plasticity, effectiveness and consequences of social pathogen defence in experimental nests of cooperatively breeding ambrosia beetles. After an
Aspergillus
spore buffer solution or a control buffer solution had been injected in laboratory nests, totipotent adult female workers increased their activity and hygienic behaviours like allogrooming and cannibalism. Such social immune responses had not been described for a non-eusocial, cooperatively breeding insect before. Removal of beetles from
Aspergillus
-treated nests in a paired experimental design revealed that the hygienic behaviours of beetles significantly reduced pathogen prevalence in the nest. Furthermore, in response to pathogen injections, female helpers delayed dispersal and thus prolonged their cooperative phase within their mother's nest. Our findings of appropriate social responses to an experimental immune challenge in a cooperatively breeding beetle corroborate the view that social immunity is not an exclusive attribute of eusocial insects, but rather a concomitant and presumably important feature in the evolutionary transitions towards complex social organization.
Vector-borne parasite invasion in communities across space and time
Authors: Vinson John E. , Park Andrew W.
Published: December 2019

While vector-borne parasite transmission often operates via generalist-feeding vectors facilitating cross-species transmission in host communities, theory describing the relationship between host species diversity and parasite invasion in these systems is underdeveloped. Host community composition and abundance vary across space and time, generating opportunities for parasite invasion. To explore how host community variation can modify parasite invasion potential, we develop a model for vector-borne parasite transmission dynamics that includes a host community of arbitrary richness and species' abundance. To compare invasion potential across communities, we calculate the community basic reproductive ratio of the parasite. We compare communities comprising a set of host species to their subsets, which allows for flexible scenario building including the introduction of novel host species and species loss. We allow vector abundance to scale with, or be independent of, community size, capturing regulation by feeding opportunities and non-host effects such as limited oviposition sites. Motivated by equivocal data relating host species competency to abundance, we characterize plausible host communities via phenomenological relationships between host species abundance and competency. We identify an underappreciated mechanism whereby changes to communities simultaneously alter average competency and the vector to host ratio and demonstrate that the interaction can profoundly influence invasion potential.
Gene drive: progress and prospects
Authors: Wedell N. , Price T. A. R. , Lindholm A. K.
Published: December 2019

Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading non-target species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release.
APOE4 status is related to differences in memory-related brain function in asymptomatic older adults: Baseline analysis of the PREVENT-AD task fMRI dataset
Authors: Rabipour Sheida , Rajagopal Sricharana , Yu Elsa , Pasvanis Stamatoula , Breitner John ,   PREVENT-AD Research Group, Rajah M. Natasha
Published: December 2019

Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer’s Disease (AD) and older adults with the apolipoprotein E e4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. In the current study we report the baseline episodic memory task fMRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT-AD) study in Montreal, Canada, in which 327 healthy older adults, within 15 years of the parent’s conversion to AD, were scanned. During the task fMRI protocol volunteers were scanned as they encodedandretrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to successful spatial source recollection and failures in spatial source recollection, with memory for only item (object) memory. Multivariate task-related partial least squares (task PLS) was used to test the hypothesis that +APOE4 adults with a family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also tested for group differences in the correlation between event-related brain activity and memory performance in +APOE4 compared to -APOE4 adults using behavioral-PLS (B-PLS). We found group similarities in memory performance and in task-related brain activity in the recollection network. However, the B-PLS results indicated there were group differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with parental history of AD. Future research should further investigate the potential to distinguish risk of AD development based on memory performance and associated patterns of brain activity.
Modelling the effects of environmental heterogeneity within the lung on the tuberculosis life-cycle
Authors: Pitcher Michael J. , Bowness Ruth , Dobson Simon , Eftimie Raluca , Gillespie Stephen H.
Published: December 2019

Progress in shortening the duration of tuberculosis (TB) treatment is hampered by the lack of a predictive model that accurately reflects the diverse environment within the lung. This is important as TB has been shown to produce distinct localisations to different areas of the lung during different disease stages, with the environmental heterogeneity within the lung of factors such as air ventilation, blood perfusion and oxygen tension believed to contribute to the apical localisation witnessed during the post-primary form of the disease.

Building upon our previous model of environmental lung heterogeneity, we present a networked metapopulation model that simulates TB across the whole lung, incorporating these notions of environmental heterogeneity across the whole TB life-cycle to show how different stages of the disease are influenced by different environmental and immunological factors. The alveolar tissue in the lung is divided into distinct patches, with each patch representing a portion of the total tissue and containing environmental attributes that reflect the internal conditions at that location. We include populations of bacteria and immune cells in various states, and events are included which determine how the members of the model interact with each other and the environment. By allowing some of these events to be dependent on environmental attributes, we create a set of heterogeneous dynamics, whereby the location of the tissue within the lung determines the disease pathological events that occur there.

Our results show that the environmental heterogeneity within the lung is a plausible driving force behind the apical localisation during post-primary disease. After initial infection, bacterial levels will grow in the initial infection location at the base of the lung until an adaptive immune response is initiated. During this period, bacteria are able to disseminate and create new lesions throughout the lung. During the latent stage, the lesions that are situated towards the apex are the largest in size, and once a post-primary immune-suppressing event occurs, it is the uppermost lesions that reach the highest levels of bacterial proliferation. Our sensitivity analysis also shows that it is the differential in blood perfusion, causing reduced immune activity towards the apex, which has the biggest influence of disease outputs.
Effects of early life glucocorticoid exposure on metabolism in zebrafish (Danio rerio) larvae
Authors: van den Bos Ruud
Published: December 2019

In this study we assessed the effects of increased cortisol levels during early embryonic development (0-6 hours post-fertilisation (hpf)), thereby mimicking maternal stress, on metabolism in zebrafish (Danio rerio) larvae. In two series of experiments fertilized eggs were exposed to a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor (GR) specifically) or a control medium for 6 hours post-fertilisation (0-6 hpf). In the first series we measured oxygen consumption as a proxy for metabolism, in the second series gene-expression of genes related to gluconeogenesis and glucose transport. Previously we have found that at 5 days post-fertilisation (dpf) baseline cortisol levels are increased following cortisol pre-treatment but not following dexamethasone pre-treatment, suggesting a higher hypothalamus-pituitary-interrenal cells (HPI-axis) activity. Hence, we hypothesized that oxygen consumption and gene-expression were stronger in cortisol-treated than in dexamethasone-treated and control-treated subjects at 5 dpf. Indeed, we observed increased oxygen consumption in cortisol-treated subjects compared to dexamethasone-treated or control-treated subjects. However, gene-expression levels were not different between treatments, which may have been due to a developmental delay in this second series. We also reasoned that both cortisol-treated and dexamethasone-treated subjects would show a higher metabolism at 1 dpf than control-treated subjects as the HPI-axis is not functional as yet and more general processes are being stimulated by cortisol through GR stimulation. Indeed, we observed increased oxygen consumption and increased expression of genes related to gluconeogenesis and glucose transport in cortisol-treated and dexamethasone-treated subjects than control-treated subjects. These data show that early-life exposure to cortisol, mimicking thereby maternal stress, increased metabolism at different life stages, i.e. 1 and 5 dpf, involving the GR.
Opening the black box of high resolution fish tracking using yaps
Authors: Baktoft Henrik , Gjelland Karl Ø. , Økland Finn , Rehage Jennifer S. , Rodemann Jonathan R. , Corujo Rolando Santos , Viadero Natasha , Thygesen Uffe H.
Published: December 2019

The R packageyapswas introduced in 2017 as a transparent open source alternative to closed source manufacturer-provided solutions to estimate positions of fish (and other aquatic animals) tagged with acoustic transmitters.

Althoughyapsis open source and transparent, the process from raw detections to final tracks has proved to be challenging for many potential users, effectively preventing most users from accessing the benefits of usingyaps. Especially, the very important process of synchronizing the hydrophone arrays have proven to be an obstacle for many potential users.

To makeyapsmore approachable to the wider fish tracking community, we have developed and added user-friendly functions assisting users in the complex process of synchronizing the data.

Here, we introduce these functions and a six-step protocol intended to provide users with an example workflow that can be used as a template enabling users to applyyapsto their own data. Using example data collected by an array of Vemco VR2 hydrophones, the protocol walks the user through the entire process from raw data to final tracks. Example data sets and complete code for reproducing results are provided.
How do backward walking ants (Cataglyphis velox) cope with navigational uncertainty?
Authors: Schwarz Sebastian , Clement Leo , Gkanias Evripides , Wystrach Antoine
Published: December 2019

Current opinion in insect navigation assumes that animals need to align with the goal direction to recognise familiar views and approach it. Yet, ants sometimes drag heavy food items backward to the nest and it is still unclear to what extent they rely on visual memories while doing so. In this study displacement experiments and alterations of the visual scenery reveal that ants do indeed recognise and use the learnt visual scenery to guide their path while walking backward. In addition, the results show that backward homing ants estimate their directional certainty by combining visual familiarity with other cues such as their path integrator and the time spent backward. A simple model that combines path integration with repulsive and attractive visual memories captures the results.
Ancient microRNA profiles of a 14,300-year-old canid are taxonomically informative and give glimpses into gene regulation from the Pleistocene
Authors: Fromm Bastian , Tarbier Marcel , Smith Oliver , Dalén Love , Gilbert M. T. P. , Friedländer Marc R.
Published: December 2019

Ancient DNA sequencing is the key technology for paleogenomic studies and today a routine method in many laboratories. Recent analyses have shown that, under favoring conditions, also RNA can be sequenced from historical and even ancient samples. We have re-analyzed ancient RNA data from a Pleistocene canid and find - in addition to the previously described messenger RNA fragments - intact microRNAs, which are short transcripts with important gene regulatory functions. With an extraordinary age of 14,300 years, the canid microRNA profiles are the oldest ever reported. Despite their age, we show that the microRNA profiles are conclusive of taxonomic origin, tissue identity with organ- and cell-type specific signatures, and that they yield glimpses into gene regulatory activity and biological processes from the Pleistocene. In summary, we here show that straightforward microRNA analyses hold great promise for deeper insights into gene regulation in extinct animals.
Separating Functions of the Phage-Encoded Quorum-Sensing-Activated Antirepressor Qtip
Authors: Silpe Justin E. , Bridges Andrew A. , Huang Xiuliang , Coronado Daniela R. , Duddy Olivia P. , Bassler Bonnie L.
Published: December 2019

Quorum sensing is a process of chemical communication that bacteria use to track cell density and coordinate gene expression across a population. Bacteria-infecting viruses, called phages, can encode quorum-sensing components that enable them to integrate host cell density information into the lysis-lysogeny decision. Vibriophage VP882 is one such phage, and activation of its quorum-sensing pathway leads to the production of an antirepressor called Qtip. Qtip interferes with the prophage repressor (cIVP882), leading to host-cell lysis. Here, we show that Qtip interacts with the N-terminus of cIVP882, inhibiting both cIVP882DNA-binding and cIVP882autoproteolysis. Qtip also sequesters cIVP882, localizing it to the poles. Qtip can localize to the poles independently of cIVP882. Alanine-scanning mutagenesis of Qtip shows that its localization and interference with cIVP882activities are separable. Comparison of Qtip to a canonical phage antirepressor reveals that, despite both proteins interacting with their partner repressors, only Qtip drives polar localization.
Enhancing vs. inhibiting semantic performance with repetitive transcranial magnetic stimulation over the anterior temporal lobe: frequency- and task- specific effects
Authors: Jung JeYoung , Lambon Ralph Matthew A.
Published: December 2019

Accumulating, converging evidence indicates that the anterior temporal lobe (ATL) appears to be the transmodal hub for semantic representation. A series of repetitive transcranial magnetic stimulation (rTMS) investigations utilizing the ‘virtual lesion’ approach have established the brain-behavioural relationship between the ATL and semantic processing by demonstrating that inhibitory rTMS over the ATL induced impairments in semantic performance in healthy individuals. However, a growing body of rTMS studies suggest that rTMS might also be a tool for cognitive enhancement and rehabilitation, though there has been no previous exploration in semantic cognition. Here, we explored a potential role of rTMS in enhancing and inhibiting semantic performance with contrastive rTMS protocols (1Hz vs. 20Hz) by controlling practice effects. Our results demonstrated that it is possible to modulate semantic performance positively or negatively depending on the ATL stimulation frequency: 20Hz rTMS was optimal for facilitating cortical processing (faster RT in a semantic task) contrasting with diminished semantic performance after 1Hz rTMS. In addition to cementing the importance of the ATL to semantic representation, our findings suggest that 20Hz rTMS leads to semantic enhancement in healthy individuals and potentially could be used for patients with semantic impairments as a therapeutic tool.
Cleavage of a pathogen apoplastic protein by plant subtilases activates immunity
Authors: Wang Shuaishuai , Xing Rongkang , Wang Yan , Shu Haidong , Fu Shenggui , Paulus Judith K. , Schuster Mariana , Saunders Diane G.O. , Win Joe , Vleeshouwers Vivianne , Zheng Xiaobo , van der Hoorn Renier A. L. , Kamoun Sophien , Dong Suomeng
Published: December 2019

The plant apoplast is a harsh environment in which hydrolytic enzymes, especially proteases, accumulate during pathogen infection. However, the defense functions of most apoplastic proteases remains largely elusive. Here, we show that a newly identified small cysteine-rich secreted protein PC2 from the potato late blight pathogenPhytophthora infestansinduces immunity in Solanum plant species only after cleavage by plant apoplastic subtilisin-like proteases, such as tomato P69B. A minimal 61-amino-acid core peptide carrying two key cysteines and widely conserved among most oomycete species is sufficient for PC2 activity. Kazal-like protease inhibitors, such as EPI1 produced byP. infestanscan prevent PC2 cleavage and dampen PC2 elicited host immunity. This study reveals that cleavage of pathogen proteins to release immunogenic peptides is an important function of apoplastic proteases but that pathogens interfere with these functions using protease inhibitor effectors.
Simulation-based comprehensive study of batch effects in metabolomics studies
Authors: Yu Miao , Roszkowska Anna , Pawliszyn Janusz
Published: December 2019

Batch effects will influence the interpretation of metabolomics data. In order to avoid misleading results, batch effects should be corrected and normalized prior to statistical analysis. Metabolomics studies are usually performed without targeted compounds (e.g., internal standards) and it is a challenging task to validate batch effects correction methods. In addition, statistical properties of metabolomics data are quite different from genomics data (where most of the currently used batch correction methods have originated from). In this study, we firstly analyzed already published metabolomics datasets so as to summarize and discuss their statistical properties. Then, based on available datasets, we developed novel statistical properties-basedin silicosimulations of metabolomics peaks’ intensity data so as to analyze the influence of batch effects on metabolomic data with the use of currently available batch correction strategies. Overall, 252000 batch corrections on 14000 differentin silicosimulated datasets and related differential analyses were performed in order to evaluate and validate various batch correction methods. The obtained results indicate that log transformations strongly influence the performance of all investigated batch correction methods. False positive rates increased after application of batch correction methods with almost no improvement on true positive rates among the analyzed batch correction methods. Hence, in metabolomic studies it is recommended to implement preliminary experiments to simulate batch effects from real data in order to select adequate batch correction method, based on a given distribution of peaks intensity. The presented study is reproducible and related R package mzrtsim software can be found online (https://github.com/yufree/mzrtsim).
Serum biochemistry suggests grey squirrels (Sciurus carolinensis) have poorer physiological condition in urban settings
Authors: Schmidt Chloé , Treberg Jason R , Kinnunen Riikka P , Garroway Colin J
Published: December 2019

Human food waste in cities presents urban wildlife with predictable, easily accessible high-calorie food sources, but this can be both beneficial and harmful for individual health. We analyzed body condition and serum chemistry (electrolyte levels, markers of kidney and liver function, protein, glucose, and cholesterol) in an urban and rural population of eastern grey squirrels (Sciurus carolinensis) to assess whether proximity to the human food waste that is associated with urban habitats had ill effects on health. We found no differences in body condition between habitats and no evidence of malnutrition at either site. However, urban squirrels had higher blood glucose, lower potassium, phosphorus, chloride, and albumin:globulin ratios. These results align with previous findings of increased dietary sugar in cities, and suggest that urban populations of grey squirrels are under greater environmental stress than rural populations.
Dynamic rotation of the protruding domain enhances the infectivity of norovirus
Authors: Song Chihong , Takai-Todaka Reiko , Miki Motohiro , Haga Kei , Fujimoto Akira , Ishiyama Ryoka , Oikawa Kazuki , Yokoyama Masaru , Miyazaki Naoyuki , Iwasaki Kenji , Murakami Kosuke , Katayama Kazuhiko , Murata Kazuyoshi
Published: December 2019

Norovirus is the major cause of epidemic nonbacterial gastroenteritis worldwide. Lack of structural information on infection and replication mechanisms hampers the development of effective vaccines and remedies. Here, using cryo-electron microscopy, we show that the capsid structure of murine noroviruses changes in response to aqueous conditions. By twisting the flexible hinge connecting two domains, the protruding (P) domain reversibly rises off the shell (S) domain in solutions of higher pH, but rests on the S domain in solutions of lower pH. Metal ions help to stabilize the latter conformation in this process. Furthermore, in the resting conformation, the cellular receptor CD300lf is readily accessible, and thus infection efficiency is significantly enhanced. Two P domain conformations were also found in the human norovirus GII.3 capsid. These results provide new insights into the infection mechanisms of the non-envelope viruses that function in dramatic environmental changes such as the digestive tract.

Significance Statement

The capsid structures of caliciviruses have been reported to be classified into two different types, according to species and genotype. One is the rising P domain type as shown in human norovirus GII.10 and rabbit hemorrhagic disease virus, where the P domain rises from the S domain surface. The other is the resting P domain type as shown in human norovirus GI.1, sapovirus and San Miguel sea lion virus, where the P domain rests upon the S domain. Here, we demonstrate that the P domain of the murine norovirus infectious particles changes reversibly between the rising and resting P domain types in response to aqueous conditions. Our findings provide new insights into the mechanisms of viral infection of caliciviruses.
Homoeologous gene expression and co-expression network analyses and evolutionary inference in allopolyploids
Authors: Hu Guanjing , Grover Corrinne E. , Arick Mark A. , Liu Meiling , Peterson Daniel G. , Wendel Jonathan F.
Published: December 2019

Polyploidy is a widespread phenomenon throughout eukaryotes. Due to the coexistence of duplicated genomes, polyploids offer unique challenges for estimating gene expression levels, which is essential for understanding the massive and various forms of transcriptomic responses accompanying polyploidy. Although previous studies have explored the bioinformatics of polyploid transcriptomic profiling, the causes and consequences of inaccurate quantification of transcripts from duplicated gene copies have not been addressed. Using transcriptomic data from the cotton genus (Gossypium) as an example, we present an analytical workflow to evaluate a variety of bioinformatic method choices at different stages of RNA-seq analysis, from homoeolog expression quantification to downstream analysis used to infer key phenomena of polyploid expression evolution. In general, GSNAP-PolyCat outperforms other quantification pipelines tested, and its derived expression dataset best represents the expected homoeolog expression and co-expression divergence. The performance of co-expression network analysis was less affected by homoeolog quantification than by network construction methods, where weighted networks outperformed binary networks. By examining the extent and consequences of homoeolog read ambiguity, we illuminate the potential artifacts that may affect our understanding of duplicate gene expression, including an over-estimation of homoeolog co-regulation and the incorrect inference of subgenome asymmetry in network topology. Taken together, our work points to a set of reasonable practices that we hope are broadly applicable to the evolutionary exploration of polyploids.
Genome-wide functional analysis of hot pepper immune receptors reveals an autonomous NLR cluster in seed plants
Authors: Lee Hye-Young , Mang Hyunggon , Choi Eun-Hye , Seo Ye-Eun , Kim Myung-Shin , Oh Soohyun , Kim Saet-Byul , Choi Doil
Published: December 2019

Plants possess hundreds of intracellular immune receptors encoding nucleotide-binding domain and leucine-rich repeat (NLR) proteins. Autoactive NLRs, in some cases a specific NLR domain, induce plant cell death in the absence of pathogen infection. In this study, we identified a group of NLRs (G10) carrying autoactive coiled-coil (CC) domains in pepper (Capsicum annuum L. cv. CM334) by genome-wide transient expression analysis. The G10-CC-mediated cell death mimics hypersensitive response (HR) cell death triggered by interaction between NLR and effectors derived from pathogens. Sequence alignment and mutagenesis analyses revealed that the intact α1 helix of G10-CCs is critical for both G10-CC- and R gene-mediated HR cell death. The cell death induced by G10-CCs does not require known helper NLRs, suggesting G10-NLRs are novel singleton NLRs. We also found that G10-CCs localize in the plasma membrane as Arabidopsis singleton NLR ZAR1. Extended studies revealed that autoactive G10-CCs are well conserved in other Solanaceae plants, including tomato, potato, and tobacco, as well as a monocot plant, rice. Furthermore, G10-NLR is an ancient form of NLR that present in all tested seed plants (spermatophytes). Our studies not only uncover the autonomous NLR cluster in plants but also provide powerful resources for dissecting the underlying molecular mechanism of NLR-mediated cell death in plants.
Improving characterization of understudied human microbiomes using targeted phylogenetics
Authors: Rosa Bruce A , Mihindukulasuriya Kathie , Hallsworth-Pepin Kymberlie , Wollam Aye , Martin John , Snowden Caroline , Dunne Wm. Michael , Weinstock George , Burnham Carey-Ann D. , Mitreva Makedonka
Published: December 2019

Whole genome bacterial sequences are required to better understand microbial functions, niches-pecific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g. stool), as few as 13% of bacterial-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from under-represented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full length 16S rRNA sequences, clustered the sequences to ensure that no individual taxonomic group was over-selected for sequencing, prioritized bacteria from under-represented body sites (such as skin, respiratory and urinary tract), and sequenced and assembled genomes for 665 new bacterial strains. Here we show that addition of these genomes improved read mapping rates of HMP metagenomic samples by nearly 30% for the previously under-represented phylumFusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and clinical perspective.

Importance

The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily stool), while other sites such as the skin, respiratory tract and urinary tracts are under-represented, resulting in as little as 13% of bacterial-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select under-represented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.
SEQing: web-based visualization of iCLIP and RNA-seq data in an interactive python framework
Authors: Lewinski Martin , Bramkamp Yannik , Köster Tino , Staiger Dorothee
Published: December 2019

Background

RNA-binding proteins interact with their target RNAs at specific sites. These binding sites can be determined genome-wide through individual nucleotide resolution crosslinking immunoprecipitation (iCLIP). Subsequently, the binding sites have to be visualized. So far, no visualization tool exists that is easily accessible but also supports restricted access so that data can be shared among collaborators.

Results

Here we present SEQing, a customizable interactive dashboard to visualize crosslink sites on target genes of RNA-binding proteins that have been obtained by iCLIP. Moreover, SEQing supports RNA-seq data that can be displayed in a diffrerent window tab. This allows, e.g. crossreferencing the iCLIP data with genes differentially expressed in mutants of the RBP and thus obtain some insights into a potential functional relevance of the binding sites. Additionally, detailed information on the target genes can be incorporated in another tab.

Conclusion

SEQing is written in Python3 and runs on Linux. The web-based access makes iCLIP data easily accessible, even with mobile devices. SEQing is customizable in many ways and has also the option to be secured by a password. The source code is available athttps://github.com/malewins/SEQing.
Genetic variation ofAedes aegyptipopulations from Ecuador
Authors: Cevallos Varsovia , Benítez Denisse , Coloma Josefina , Carrazco Andrés , Wang Chunling , Holecheck Susan , Quiroga Cristina , Castillo Gabriela , Tillis Britney , Ponce Patricio
Published: December 2019

This is the first genetic analysis in Ecuador ofAedes aegyptiusing fragments of mitochondrial genes, NADH dehydrogenase subunit 4 (ND4) and cytochrome oxidase subunit I (COI). A total of 154 mosquitoes from 23 localities were collected in the Pacific coastal lowlands, Amazon basin lowlands, and the Galápagos Islands from 2012 to 2019. The analysis of fragments of the genes COI (672 bp) and ND4 (262 bp) and concatenated analysis of both COI and ND4 showed two haplotypes (H1, H2) present in Ecuador mainland and the Galápagos Islands. The phylogenetic analysis identified two well-supported clades. Combined analysis of both genes from ten localities also resulted in two haplotypes. Nucleotide diversity, neutrality tests (Tajima’s test D, Fu and Li’s F*and D*) and AMOVA analysis of the entire data set suggest balancing selection for both genes. The results indicate genetic variation without geographical restriction. COI-H1 grouped with sequences from the Americas, West and Central Africa, East Africa, Asia, and Australia. ND4-H1 grouped with similar sequences from the Americas, Asia and West Africa. COI-H2 grouped with sequences from Asia and the Americas. ND4-H2 grouped with sequences from the Americas. We report overlapping peaks in four sequences that suggest heteroplasmy in the individuals. The origin of the populations ofAedes aegyptiin Ecuador show African genetic origin and are widely present in several countries in the Americas. One of the genetic variants is more common in all the localities and the two haplotypes are distributed indistinctly in the three geographical sampled areas in Ecuador.