bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Fetalization of Enhancer Architecture in Heart Disease
Authors: Spurrell Cailyn H. , Barozzi Iros , Mannion Brandon J. , Blow Matthew J. , Fukuda-Yuzawa Yoko , Afzal Sarah Y. , Akiyama Jennifer A. , Afzal Veena , Tran Stella , Plajzer-Frick Ingrid , Novak Catherine S. , Kato Momoe , Lee Elizabeth , Garvin Tyler H. , Pham Quan T. , Harrington Anne N. , Lisgo Steven , Bristow James , Cappola Thomas P. , Morley Michael P. , Margulies Kenneth B. , Pennacchio Len A. , Dickel Diane E. , Visel Axel
Published: April 2019

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the genome-wide regulatory landscape in heart disease has remained obscure. Here we show that pervasive epigenomic changes occur in heart disease, with thousands of regulatory sequences reacquiring fetal-like chromatin signatures. We used RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from 18 healthy controls and 18 individuals with idiopathic dilated cardiomyopathy (DCM). Healthy individuals had a highly reproducible epigenomic landscape, consisting of more than 31,000 predicted heart enhancers. In contrast, we observed reproducible disease-associated gains or losses of activity at more than 7,500 predicted heart enhancers. Next, we profiled human fetal heart tissue by ChIP-seq and RNA-seq. Comparison with adult tissues revealed that the heart disease epigenome and transcrip-tome both shift toward a fetal-like state, with 3,400 individual enhancers sharing fetal regulatory properties. Our results demonstrate widespread epigenomic changes in DCM, and we provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of heart disease etiology.
Performance of bitumen coating sheet using biomass pyrolysis oil
Authors: Ren Yanru , Zhang Lei , Duan Wenfeng , Guo Jia , Han Zhongqiang , Heydenrych Michael D. , Zhang Aijun , Nie Kaili , Tan Tianwei , Liu Luo
Published: April 2019

The “green” production of bitumen has raised increasing interest in recent years to reduce the environmental, energy and petro-based concerns. Bio-oil, prepared by biomass pyrolysis, can be used as substitute for petro-based bitumen in bitumen or bitumen-based coatings, for its similar properties of good adhesion and anti-corrosion characteristics. Although biomass is a renewable and widespread chemicals resource, its value-added utilization is still difficult. Several studies have qualitatively demonstrated the use of bio-bitumen in practical applications. The present study investigates the effects and properties and the incorporation of bio-bitumen shown to improve the performance of traditional petro-bitumen to some extent. Bio-bitumen was prepared from biomass pyrolysis oil and applied to self-adhesive and doped hot-melt sheets. Resulting physical properties demonstrate that bio-bitumen is a potential substitute in bitumen coating sheet.

IMPLICATIONS

This paper is intended to verify the effect of pyrolyzed bio-oil from wheat straw on the performance of bitumen, as well as the feasibility of application in the coating sheet. Up to now, the research on bio-bitumen is mainly in pavement bitumen. In the present research, bio-bitumen was applied to the coating sheet in different proportions. Interestingly, the prepared coating sheet exhibited higher adhesion. Other performances, such as temperature stability, mechanical strength and temperature flexibility of coating sheet showed improvement in the presence of bio- oil, which indicated the suitability of bio-oil in coating sheet bitumen.
Fronto-striatal Functional Connectivity Supports Reward-Enhanced Memory in Older Adults
Authors: Bowen Holly J. , Ford Jaclyn H. , Grady Cheryl L. , Spaniol Julia
Published: April 2019

Both younger and older adults prioritize reward-associated stimuli in memory, but there has been little research on possible age differences in the neural mechanisms mediating this effect. In the current study, we examine neural activation and functional connectivity in healthy younger and older adults to test the hypothesis that older adults would engage prefrontal regions to a greater extent in the service of reward-enhanced memory. While undergoing MRI, target stimuli were presented after high or low-reward cues. The cues indicated the reward value for successfully recognizing the stimulus on a memory test 24-hours later. We replicated prior findings that both older and younger and adults had better memory for high compared to low-reward stimuli. Critically, in older, but not younger adults, this enhanced subsequent memory for high-reward items was supported by greater connectivity between the caudate and bilateral inferior frontal gyrus. The findings add to the growing literature on motivation-cognition interactions in healthy aging, and provide novel evidence of an age-related shift in the neural underpinnings of reward-motivated encoding.
Quantifying shape, integration, and ecology in avian pedal claws: comparing geometric morphometric and traditional metric approaches
Authors: Hedrick Brandon P. , Cordero Samantha A. , Zanno Lindsay E. , Noto Christopher , Dodson Peter
Published: April 2019

Terrestrial tetrapods use their claws to interact with their environments in a plethora of ways. Birds in particular have developed a diversity of claw shapes since they are not bound to terrestrial locomotion and have heterogeneous body masses ranging several orders of magnitude. Numerous previous studies have hypothesized a connection between pedal claw shape and ecological mode in birds, but have generated conflicting results, spanning from clear ecological groupings based on claw shape to a complete overlap of ecological modes. These studies have relied on traditional morphometric arc measurements of keratinous sheaths and have variably accounted for likely confounding factors such as body mass and phylogenetic relatedness. To better address the hypothesized relationship between ecology and claw shape in birds, 580 radiographs were collected allowing visualization of the bony core and keratinous sheath shape spanning 21 avian orders. A new method was used to quantify claw shape using geometric morphometrics and was compared to results using traditional arc measurements. Neither traditional nor geometric morphometrics are capable of significantly separating bird claws into coarse ecological categories after integrating body size and phylogenetic relatedness. Further, the bony claw core and keratinous sheath are significantly integrated with one another, suggesting that they function as a single unit. Therefore, it is likely possible to compare fossil bony cores with extant keratinous sheaths after applying corrections. Finally, traditional metrics and geometric morphometric shape are significantly, yet loosely correlated, and geometric morphometric data better distinguish ecological groups in morphospace than is possible with traditional metrics. Based on these results, future workers are encouraged to use geometric morphometric approaches to study claw geometry and account for confounding factors such as body size, phylogeny, and individual variation prior to predicting ecology in fossil taxa.
A novel phyllosphere residentProtomycesspecies that interacts with theArabidopsisimmune system
Authors: Wang Kai , Sipilä Timo , Rajaraman Sitaram , Safronov Omid , Laine Pia , Auzane Agate , Mari Alfredo , Auvinen Petri , Paulin Lars , Kemen Eric , Salojärvi Jarkko , Overmyer Kirk
Published: April 2019

We describe the genome contents of sixProtomycesspp. that are pathogenic within the typical host range of the genus and a novelProtomycesstrain (SC29) that was previously isolated from the phylloplane of wildArabidopsis thaliana(Arabidopsis), an atypical or possible alternate host. Genome-wide phylogenetic analysis defined SC29 as a distinctProtomycessp. Analysis of gene family expansions, gene retention, and gene loss patterns among theseProtomycesspp. lead us to hypothesize that SC29 may have undergone a host jump. The role of phyllosphere residency in the lifecycle ofProtomycesspp. was previously unknown. Genomic changes in SC29 and all otherProtomycesspp. were consistent with adaptations to the plant phylloplane. As predicted by our analysis of its mating locus, SC29 did not cause disease onArabidopsisas a single strain, but could persist in its phylloplane, while the closely relatedP. inouyeidoes not. SC29 treatedArabidopsisexhibited enhanced immunity againstBotrytis cinereainfection, associated with activation of MAPK3/6, camalexin, and SA-signalling pathways. We conclude that SC29 is a novelProtomycessp. able to survive in theArabidopsisphylloplane and that phylloplane residency is an important element in the lifecycle ofProtomycesspp.
A three-sample test for introgression
Authors: Hahn Matthew W. , Hibbins Mark S.
Published: April 2019

Many methods exist for detecting introgression between non-sister species, but the most commonly used require either a single sequence from four or more taxa or multiple sequences from each of three taxa. Here we present a test for introgression that uses only a single sequence from three taxa. This test, denoted D3, uses similar logic as the standard D-test for introgression, but by using pairwise distances instead of site patterns it is able to detect the same signal of introgression with fewer species. We use simulations to show that D3 has statistical power almost equal to D, demonstrating its use on a dataset of wild bananas (Musa). The new test is easy to apply and easy to interpret, and should find wide use among currently available datasets.
A vibrating mesh nebulizer as an alternative to the Collison 3-jet nebulizer for infectious disease aerobiology
Authors: Bowling Jennifer D. , O’ Malley Katherine J. , Klimstra William B. , Hartman Amy L. , Reed Douglas S.
Published: April 2019

Experimental infection of animals via inhalation containing pathogenic agents is essential to understanding the natural history and pathogenesis of infectious disease as well as evaluation of potential medical countermeasures. We evaluated whether the Aeroneb, a vibrating mesh nebulizer, would serve as an alternative to the Collison, the ‘gold standard’ for generating infectious bioaerosols. While the Collison possesses desirable properties that have contributed to its longevity in infectious disease aerobiology, concerns have lingered about the volume and concentration of agent required to cause disease and the damage that jet nebulization causes to the agent. For viruses, the ratio of aerosol concentration to nebulizer concentration (spray factor, SF), the Aeroneb was superior to the Collison for four different viruses in a nonhuman primate head-only exposure chamber. Aerosol concentration of influenza was higher relative to fluorescein for the Aeroneb compared to the Collison, suggesting that the Aeroneb was less harsh to viral pathogens than the Collison when generating aerosols. The Aeroneb did not improve the aerosol SF for a vegetative bacterium,Francisella tularensis.Environmental parameters collected during the aerosols indicated that the Aeroneb generated a higher relative humidity in exposure chambers while not affecting other environmental parameters. Aerosol mass median aerodynamic diameter was generally larger and more disperse for aerosols generated by the Aeroneb than what is seen with the Collison but ≥80% were within the range that would reach the lower respiratory tract and alveolar regions. These data suggest that for viral pathogens, the Aeroneb is a suitable alternative to the Collison 3-jet nebulizer.

Importance

The threat of aerosolization is often not the natural method of transmission. While selection of an appropriate animal model is vital for these types of experiments, other confounding factors can be controlled through a thorough understanding of experimental design and the effects that different parameters can have on disease outcome. Route of administration, particle size, and dose are all factors which can affect disease progression and need to be controlled. Aerosol research methods and equipment need to be well characterized to optimize the development of animal models for bioterrorism agents.
Three new integration vectors and fluorescent proteins for use in the opportunistic human pathogenStreptococcus pneumoniae
Authors: Keller Lance E. , Rueff Anne-Stéphanie , Kurushima Jun , Veening Jan-Willem
Published: April 2019

Here we describe the creation of three integration vectors, pPEPX, pPEPY and pPEPZ, for use with the opportunistic human pathogenStreptococcus pneumoniae. The constructed vectors, named PEP for Pneumococcal Engineering Platform, employ an IPTG-inducible promoter and BglBrick and BglFusion compatible multiple cloning sites allowing for fast and interchangeable cloning. PEP plasmids replicate inEscherichia coliand harbor integration sites that have homology in a large set of pneumococcal strains, including recent clinical isolates. In addition, several options of antibiotic resistance markers are available, even allowing for selection in multidrug resistant clinical isolates. The transformation efficiency of these PEP vectors as well as their ability to be expressed simultaneously were tested. Two of the three PEP vectors share homology of the integration regions with over half of theS. pneumoniaegenomes examined. Transformation efficiency varied among PEP vectors based on the length of the homology regions, but all were highly transformable and can be integrated simultaneously in strain D39V. Vectors used for pneumococcal cloning are an important tool for researchers for a wide range of uses. The PEP vectors described are of particular use because they have been designed to allow for easy transfer of genes between vectors as well as integrating into transcriptionally silent areas of the chromosome. In addition, we demonstrate the successful production of several new spectrally distinct fluorescent proteins (mTurquoise2, mNeonGreen and mScarlet-I) from the PEP vectors. The PEP vectors and newly described fluorescent proteins will expand the genetic toolbox for pneumococcal researchers and aid future discoveries.
Classification of Neurons in the Adult Mouse Cochlear Nucleus: Linear Discriminant Analysis
Authors: Manis Paul B. , Kasten Michael R. , Xie Ruili
Published: April 2019

The cochlear nucleus (CN) transforms the spike trains of spiral ganglion cells into a new set of sensory representations that are essential for auditory discriminations and perception. These transformations require the coordinated activity of different classes of neurons that are embryologically derived from distinct sets of precursors. Decades of investigation have shown that the neurons of the CN are differentiated by their ion channel expression and intrinsic excitability. In the present study we have used linear discriminant analysis (LDA) to perform an unbiased analysis of measures of the responses of CN neurons to current injections to mathematically separate cells on the basis of both morphology and physiology. Recordings were made from cells in brain slices from CBA mice and a transgenic mouse line, NF107, crossed against the Ai32 line. For each cell, responses to current injections were analyzed for spike rate, spike shape (action potential height, afterhyperpolarization depth, first spike half-width), input resistance, resting membrane potential, membrane time constant, hyperpolarization-activated sag and time constant. Cells were filled with dye for morphological classification, and visually classified according to published accounts. The different morphological classes of cells were separated with the LDA. Ventral cochlear nucleus (VCN) bushy cells, planar multipolar (T-stellate) cells, and radiate multipolar (D-stellate) cells were in separate clusters, and were also separated from all of the neurons from the dorsal cochlear nucleus (DCN). Within the DCN, the pyramidal cells and tuberculoventral cells were largely separated from a distinct clusters of cartwheel cells. DCN cells fell largely within a plane in the first 3 principal axes, whereas VCN cells were in 3 clouds approximately orthogonal to this plane. VCN neurons from the two mouse strains were slightly separated, indicating either a strain dependence or the differences in slice preparation methods. We conclude that cochlear nucleus neurons can be objectively distinguished based on their intrinsic electrical properties, but that such distinctions are still best aided by morphological identification.
Early Reactivation of Emotion in ERPs to Neutral Retrieval Cues
Authors: Bowen Holly J. , Fields Eric C. , Kensinger Elizabeth A.
Published: April 2019

Memory retrieval is thought to involve the reactivation of encoding processes. Previous fMRI work has indicated that reactivation processes are modulated by the residual effects of the prior emotional encoding context; different spatial patterns emerge during retrieval of memories previously associated with negative compared to positive or neutral context. Other research suggests that ERP indicators of memory retrieval processes, like the left parietal old/new effect, can also be modulated by emotion, but the spatial distribution and temporal dynamics of these effects is unclear. In the current study, we examinedwhenemotion affects memory reactivation and whether that timing reflects processes that come before and may guide successful retrieval or post-recollection recovery of emotional episodic detail. While recording EEG, participants (N = 25) viewed neutral words paired with negative, positive or neutral pictures during encoding, followed by a recognition test for the words. Analyses focused on ERPs during the recognition test. In line with prior ERP studies, we found an early positive-going parietally distributed effect starting around 200 ms post retrieval-cue onset. This effect emerged for words that had been encoded in an emotional compared to neutral context (no valence differences), before the general old/new effect. This emotion-dependent effect occurred in an early time window, suggesting emotion-related reactivation is a precursor to successful recognition.
Integrating case studies into graduate teaching assistant training to improve instruction in biology laboratory courses
Authors: Kraft Jelena , Walck-Shannon Elise , Reilly Colleen , Stapleton Ann E
Published: April 2019

Today’s biology laboratory courses are primarily instructed by graduate teaching assistants (GTAs) working toward their own graduate degrees in a science field. Even though GTAs are the driving instructional force in biology laboratories, they receive little to no training in pedagogical principles and applications. Here, we present the GTAs’ self-reported unmet training needs with respect to teaching biology laboratory courses. To address these needs, we developed three training cases along with instructions for implementation in online and in-person GTA trainings. We piloted our training materials for GTA training in person at Iowa State University and in a Center for the Integration of Research, Teaching, and Learning three-part online workshop. Upon completion of these training sessions, GTAs reported an increase in both their confidence and knowledge of student-centered instructional approaches. Furthermore, examination of the online workshop participants’ lesson plans demonstrated that GTAs were able to implement effective teaching practices in their own lesson plans. For brief training sessions, these are positive outcomes suggesting these cases are effective tools that could be incorporated into a variety of GTA training programs to improve instruction in biology laboratory courses.
Mini-barcodes are equally useful for species identification and more suitable for large-scale species discovery in Metazoa than full-length barcodes
Authors: Yeo Darren , Srivathsan Amrita , Meier Rudolf
Published: April 2019

New techniques for the species-level sorting of millions of specimens are needed in order to accelerate species discovery, determine how many species live on earth, and develop efficient biomonitoring techniques. These sorting methods should be reliable, scalable and cost-effective, as well as being largely insensitive to low-quality genomic DNA, given that this is usually all that can be obtained from museum specimens. Mini-barcodes seem to satisfy these criteria, but it is unclear how well they perform for species-level sorting when compared to full-length barcodes. This is here tested based on 20 empirical datasets covering ca. 30,000 specimens and 5,500 species, as well as six clade-specific datasets from GenBank covering ca. 98,000 specimens for over 20,000 species. All specimens in these datasets had full-length barcodes and had been sorted to species-level based on morphology. Mini-barcodes of different lengths and positions were obtainedin silicofrom full-length barcodes using a sliding window approach (3 windows: 100-bp, 200-bp, 300-bp) and by excising nine mini-barcodes with established primers (length: 94 – 407-bp). We then tested whether barcode length and/or position reduces species-level congruence between morphospecies and molecular Operational Taxonomic Units (mOTUs) that were obtained using three different species delimitation techniques (PTP, ABGD, objective clustering). Surprisingly, we find no significant differences in performance for both species- or specimen-level identification between full-length and mini-barcodes as long as they are of moderate length (>200-bp). Only very short mini-barcodes (<200-bp) perform poorly, especially when they are located near the 5’ end of the Folmer region. The mean congruence between morphospecies and mOTUs is ca. 75% for barcodes >200-bp and the congruent mOTUs contain ca. 75% of all specimens. Most conflict is caused by ca. 10% of the specimens that can be identified and should be targeted for re-examination in order to efficiently resolve conflict. Our study suggests that large-scale species discovery, identification, and metabarcoding can utilize mini-barcodes without any demonstrable loss of information compared to full-length barcodes.
Optimal policy for multi-alternative decisions
Authors: Tajima Satohiro , Drugowitsch Jan , Patel Nisheet , Pouget Alexandre
Published: April 2019

Every-day decisions frequently require choosing among multiple alternatives. Yet, the optimal policy for such decisions is unknown. Here we derive the normative policy for general multi-alternative decisions. This strategy requires evidence accumulation to nonlinear, time-dependent bounds, that trigger choices. A geometric symmetry in those boundaries allows the optimal strategy to be implemented by a simple neural circuit involving a normalization with fixed decision bounds and an urgency signal. The model captures several key features of the response of decision-making neurons as well as the increase in reaction time as a function of the number of alternatives, known as Hick’s law. In addition, we show that, in the presence of divisive normalization and internal variability, our model can account for several so called ‘irrational’ behaviors such as the similarity effect as well as the violation of both the independent irrelevant alternative principle and the regularity principle.
Weighted burden analysis of exome-sequenced late onset Alzheimer’s cases and controls provides further evidence for a role for PSEN1 and suggests involvement of the PI3K/Akt/GSK-3β and WNT signalling pathways
Authors: Curtis David , Bakaya Kaushiki , Sharma Leona , Bandyopadhyay Sreejan
Published: April 2019

Previous studies have implicated common and rare genetic variants as risk factors for late onset Alzheimer’s disease (AD, LOAD). Here, weighted burden analysis was applied to over 10,000 exome sequenced subjects from the Alzheimer’s Disease Sequencing Project. Analyses were carried out to investigate whether rare variants predicted to have a functional effect within a gene were more commonly seen in cases or in controls. Confirmatory results were obtained for TREM2, ABCA7 and SORL1. Additional support was provided for PSEN1 (p = 0.0002), which previously had been only weakly implicated in LOAD. There was suggestive evidence that functional variants in PIK3R1, WNT7A, C1R and EXOC5 might increase risk and that variants in TIAF1 and/or NDRG2 might have a protective effect. Overall, there was strong evidence (p = 5 × 10−6) that variants in tyrosine phosphatase genes reduce the risk of developing LOAD. Since PIK3R1 variants are expected to impair PI3K/Akt/GSK-3β signalling while variants in tyrosine phosphatase genes would enhance it, these findings are in line with those from animal models suggesting that this pathway is protective against AD.
Managing congestion at visitor hotspots using park-level use level data: Case study of a Chinese World Heritage site
Authors: Guo Jin-Hui , Guo Tian , Lin Kai-Miao , Leung Yu-Fai , Chen Qiu-Hua
Published: April 2019

Tourist congestion at hot spots has been a major management concern for UNESCO World Heritage Sites and other iconic protected areas. A growing number of heritage sites employ technologies, such as cameras and electronic ticket-checking systems, to monitor user levels, but data collected by these monitoring technologies are often under-utilize. In this study, we illustrated how to integrate data from hot spots by camera-captured monitoring and entrance counts to manage use levels at a World Heritage Site in southeastern China. 6,930 photos of a congestion hotspot (scenic outlook on a trail) were collected within the park at a 10-minute interval over 105 days from January to November 2017. The entrance counts were used to predict daily average and maximum use level at the hotspot Average use level at the congestion hotspot did not exceed the use limit mandated by the Chinese park administration agency. However, from 9:20 am to 12:00 pm, the use level at hotspots exceeded visitor preferred use level. Visitor use level was significantly higher at the hotspot during a major Chinese “golden week” holiday. The daily entrance counts significantly predicted the average and maximum use level at the hotspot. Based on our findings, we recommend that the number of visitors entering the gate on each day should be less than 28,764 for the hotspots to meet use level mandates, while less than 6,245 to meet visitor preference. The gap manifested the complexity in visitor capacity management at high-use World Heritage Sites and other protected areas and calls for innovative monitoring and management strategies.
Understanding patterns of abiotic and biotic stress resilience to unleash the potential of crop wild relatives for climate-smart legume breeding
Authors: van Zonneveld Maarten , Rakha Mohamed , Tan Shin-yee , Chou Yu-yu , Chang Ching-huan , Yen Joyce , Schafleitner Roland , Nair Ramakrishnan , Naito Ken , Solberg Svein Ø.
Published: April 2019

Although new varieties are urgently needed for climate-smart legume production, legume breeding lags behind with cereals and underutilizes wild relatives. This paper provides insights in patterns of abiotic and biotic stress resilience of legume crops and wild relatives to enhance the use and conservation of these genetic resources for climate-smart legume breeding. We focus onVigna, a pantropical genus with more than 88 taxa including important crops such as cowpea and mung bean. Sources of pest and disease resistance occur in more than 50 percent of theVignataxa, which were screened while sources of abiotic stress resilience occur in less than 20 percent of the taxa, which were screened. This difference suggests thatVignataxa co-evolve with pests and diseases while taxa are more conservative to adapt to climatic changes and salinization. Twenty-twoVignataxa are poorly conserved in genebanks or not at all. This germplasm is not available for legume breeding and requires urgent germplasm collecting before these taxa extirpate on farm and in the wild.Vignataxa, which tolerate heat and drought stress are rare compared with taxa, which escape these stresses or tolerate salinity. These rareVignataxa should be prioritized for conservation and screening for multifunctional traits of combined abiotic and biotic stress resilience. The high presence of salinity tolerance compared with drought stress tolerance, suggests thatVignataxa are good at developing salt-tolerant traits compared with drought-tolerant traits.Vignataxa are therefore of high value for legume production in areas that suffer from salinization.
Landowner Functional Types to Characterize Response to Forest Insects
Authors: Holt Jonathan R. , Borsuk Mark E. , Butler Brett J. , Kittredge David B. , Laflower Danelle , MacLean Meghan Graham , Markowski-Lindsay Marla , Orwig David , Thompson Jonathan R.
Published: April 2019

Forest insects and pathogens (FIPs) play an important role in the complex interactions between woodland owners and the ecosystems they manage. Understanding the specifics of woodland owner decision-making with regard to trees impacted by FIPs can facilitate projections of future forest conditions and insect spread. Our first objective is to: (i) characterize agent functional types (AFTs) of New England family forest owners (FFOs) using a set of contingent behavior questions contained in a mail survey of FFOs concerning response to FIPs. We establish AFTs as a form of dimension reduction, effectively assigning individual FFOs to particular decision-making classes, each with distinct probabilities of behavior with respect to the harvest of impacted trees. Our second objective is to: (ii) model AFT membership to predict the distribution of AFTs across the landscape. Predictors are chosen from a set of survey, geographic, and demographic features. Accomplishing (i) establishes three functional classes of landowners: ‘cutters’ (46% of respondents; highly likely to cut timber impacted by FIPs), ‘responsive’ cutters (42% of respondents; sensitive to pest severity), and ‘non-cutters’ (12% of respondents; highly unlikely to cut). Fulfilling (ii) provides a high-resolution probability surface of AFTs across the landscape, delivering key input for simulation models of forest and land cover change in New England. Predictors in our best model of AFT membership include parcel size (hectares of forest), region, and town-level forested fraction.
Disambiguating the role of blood flow and global signal with Partial Information Decomposition
Authors: Colenbier Nigel , Van de Steen Frederik , Uddin Lucina Q. , Poldrack Russell A. , Calhoun Vince D. , Marinazzo Daniele
Published: April 2019

In resting state functional magnetic resonance imaging (rs-fMRI) a common strategy to reduce the impact of physiological noise and other artifacts on the data is to regress out the global signal using global signal regression (GSR). Yet, GSR is one of the most controversial preprocessing techniques for rs-fMRI. It effectively removes non-neuronal artifacts, but at the same time it alters correlational patterns in unpredicted ways. Furthermore the global signal includes neural BOLD signal by construction, and is consequently related to neural and behavioral function. Performing GSR taking into account the underlying physiology (mainly the blood arrival time) has been proved to be beneficial. From these observations we aimed to: 1) characterize the effect of GSR on network-level functional connectivity in a large dataset; 2) assess the complementary role of global signal and vessels; and 3) use the framework of partial information decomposition to further look into the joint dynamics of the global signal and vessels, and their respective influence on the dynamics of cortical areas. We observe that GSR affects intrinsic connectivity networks in the connectome in a non-uniform way. Furthermore, by estimating the predictive information of blood flow and the global signal using partial information decomposition, we observe that both signals are present in different amounts across intrinsic connectivity networks. Simulations showed that differences in blood arrival time can largely explain this phenomenon. With these results we confirm network-specific effects of GSR and the importance of taking blood flow into account for improve denoising methods. Using GSR but not correcting for blood flow might selectively introduce physiological artifacts across intrinsic connectivity networks that distort the functional connectivity estimates.
Horizontal gene transfer by natural transformation promotes both genetic and epigenetic inheritance of traits
Authors: Dalia Ankur B. , Dalia Triana N.
Published: April 2019

Natural transformation (NT) is a major mechanism of horizontal gene transfer in microbial species that promotes the spread of antibiotic resistance determinants and virulence factors. Here, we develop a cell biological approach to characterize the spatial and temporal dynamics of homologous recombination during NT inVibrio cholerae. Our results directly demonstrate (1) that transforming DNA efficiently integrates into the genome as single-stranded DNA, (2) that the resulting heteroduplexes are resolved by chromosome replication and segregation, and (3) that integrated DNA is rapidly expressed prior to cell division. We show that the combination of these properties results in the epigenetic transfer of gene products within transformed populations, which can support the transgenerational epigenetic inheritance of antibiotic resistance in bothV. choleraeandStreptococcus pneumoniae. Thus, beyond the genetic acquisition of novel DNA sequences, NT can also promote the epigenetic inheritance of traits during this conserved mechanism of horizontal gene transfer.
Associated organisms inhabiting the calcareous spongeClathrina luteain La Parguera Natural Reserve, Puerto Rico
Authors: García-Hernández Jaaziel E. , Hammerman Nicholas M. , Cruz-Motta Juan J. , Schizas Nikolaos V.
Published: April 2019

Sponges provide an array of ecological services and benefits for Caribbean coral reefs. They function as habitats for a bewildering variety of species, however limited attention has been paid in the systematics and distribution of sponge-associated fauna in the class Calcarea or for that matter of sponges in the Caribbean. The goal of this study was to characterize infaunal assemblages from a calcareous sponge,Clathrina lutea, across multiple reefs from the La Parguera Natural Reserve, Puerto Rico. The associated fauna from 43C. luteaspecimens yielded a total of 2,249 associated infauna distributed in seven invertebrate phyla. Arthropoda was the most abundant phylum accounting for 62.5% of total abundance, followed by Annelida (21.0%) and Nematoda (5.5%). Limited patterns of temporal or spatial variability were surmised due to the opportunistic sampling effort afforded to this investigation from the cryptic nature of this species. A concordance between our data set and those for the class Demospongiae were observed, with the most abundant associated fauna being copepods and polychaetes. However, when compared to other Calcarea, the present study found considerably more associated fauna.
OpenAnnotate: a web server to annotate the chromatin accessibility of genomic regions
Authors: Chen Shengquan , Liu Qiao , Cui Xuejian , Feng Zhanying , Li Chunquan , Wang Xiaowo , Zhang Xuegong , Wang Yong , Jiang Rui
Published: April 2019

Chromatin accessibility, as a powerful marker of active DNA regulatory elements, provides valuable information for understanding regulatory mechanisms. The revolution in high-throughput methods has accumulated massive chromatin accessibility profiles in public repositories. Nevertheless, utilization of these data is hampered by cumbersome collection, time-consuming processing, and manual chromatin accessibility (openness) annotation of genomic regions. To fill this gap, we developed OpenAnnotate (http://health.tsinghua.edu.cn/openannotate/) as the first web server for efficiently annotating openness of massive genomic regions across various biosample types, tissues, and biological systems. In addition to the annotation resource from 2729 comprehensive profiles of 614 biosample types of human and mouse, OpenAnnotate provides user-friendly functionalities, ultra-efficient calculation, real-time browsing, intuitive visualization, and elaborate application notebooks. We show its unique advantages compared to existing databases and toolkits by effectively revealing cell type-specificity, identifying regulatory elements and 3D chromatin contacts, deciphering gene functional relationships, inferring functions of transcription factors, and unprecedentedly promoting single-cell data analyses. We anticipate OpenAnnotate will provide a promising avenue for researchers to construct a more holistic perspective to understand regulatory mechanisms.
The brain detects stimulus features, but not stimulus conflict in task-irrelevant sensory input
Authors: Nuiten Stijn A. , Canales-Johnson Andrés , Beerendonk Lola , Nanuashvili Nutsa , Fahrenfort Johannes J. , Bekinschtein Tristan , van Gaal Simon
Published: April 2019

Cognitive control over conflicting sensory input is central to adaptive human behavior. It might therefore not come as a surprise that past research has shown conflict detection in the absence of conscious awareness. This would suggest that the brain may detect conflict fully automatically, and that it can even occur without paying attention. Contrary to this intuition, we show that task-relevance is crucial for conflict detection. Univariate and multivariate analyses on electroencephalographic data from human participants revealed that when auditory stimuli are fully task-irrelevant, the brain disregards conflicting input entirely, whereas the same input elicits strong neural conflict signals when task-relevant. In sharp contrast, stimulus features were still processed, irrespective of task-relevance. These results show that stimulus properties are only integrated to allow conflict to be detected by prefrontal regions when sensory information is task-relevant and therefore suggests an attentional bottleneck at high levels of information analysis.
Integrative protein modeling in RosettaNMR from sparse paramagnetic restraints
Authors: Kuenze Georg , Bonneau Richard , Leman Julia Koehler , Meiler Jens
Published: April 2019

Computational methods to predict protein structure from nuclear magnetic resonance (NMR) restraints that only require assignment of backbone signals hold great potential to study larger proteins and complexes. Additionally, computational methods designed to work with sparse data add atomic detail that is missing in the experimental restraints, allowing application to systems that are difficult to investigate. While specific frameworks in the Rosetta macromolecular modeling suite support the use of certain NMR restraint types, use of all commonly measured restraint types together is precluded. Here, we introduce a comprehensive framework into Rosetta that reconciles CS-Rosetta, PCS-Rosetta and RosettaNMR into a single framework, that, in addition to backbone chemical shifts and nuclear Overhauser effect distance restraints, leverages NMR restraints derived from paramagnetic labeling. Specifically, RosettaNMR incorporates pseudocontact shifts, residual dipolar couplings, and paramagnetic relaxation enhancements, measured at multiple tagging sites. We further showcase the generality of RosettaNMR for various modeling challenges and benchmark it on 28 structure prediction cases, eight symmetric assemblies, two protein-protein and three protein-ligand docking examples. Paramagnetic restraints generated more accurate models for 85% of the benchmark proteins and, when combined with chemical shifts, sampled high-accuracy models (≤ 2Å) in 50% of the cases.

Significance Statement

Computational methods such as Rosetta can assist NMR structure determination by employing efficient conformational search algorithms alongside physically realistic energy functions to model protein structure from sparse experimental data. We have developed a framework in Rosetta that leverages paramagnetic NMR data in addition to chemical shift and nuclear Overhauser effect restraints and extends RosettaNMR calculations to the prediction of symmetric assemblies, protein-protein and protein-ligand complexes. RosettaNMR generated high-accuracy models (≤ 2Å) in 50% of cases for a benchmark set of 28 monomeric and eight symmetric proteins and predicted protein-protein and protein-ligand interfaces with up to 1Å accuracy. The method expands Rosetta’s rich toolbox for integrative data-driven modeling and promises to be broadly useful in structural biology.
Efficient and unique cobarcoding of second-generation sequencing reads from long DNA molecules enabling cost-effective and accurate sequencing, haplotyping, and de novo assembly
Authors: Wang Ou , Chin Robert , Cheng Xiaofang , Wu Michelle Ka Yan , Mao Qing , Tang Jingbo , Sun Yuhui , Anderson Ellis , Lam Han K. , Chen Dan , Zhou Yujun , Wang Linying , Fan Fei , Zou Yan , Xie Yinlong , Zhang Rebecca Yu , Drmanac Snezana , Nguyen Darlene , Xu Chongjun , Villarosa Christian , Gablenz Scott , Barua Nina , Nguyen Staci , Tian Wenlan , Liu Jia Sophie , Wang Jingwan , Liu Xiao , Qi Xiaojuan , Chen Ao , Wang He , Dong Yuliang , Zhang Wenwei , Alexeev Andrei , Yang Huanming , Wang Jian , Kristiansen Karsten , Xu Xun , Drmanac Radoje , Peters Brock A.
Published: April 2019

Here, we describe single-tube long fragment read (stLFR), a technology that enables sequencing of data from long DNA molecules using economical second-generation sequencing technology. It is based on adding the same barcode sequence to subfragments of the original long DNA molecule (DNA cobarcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process, up to 3.6 billion unique barcode sequences were generated on beads, enabling practically nonredundant cobarcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique cobarcoding of more than 8 million 20- to 300-kb genomic DNA fragments. Analysis of the human genome NA12878 with stLFR demonstrated high-quality variant calling and phase block lengths up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries, and their construction did not significantly add to the time or cost of whole-genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high-quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.
Design and performance of a new setup for spatially resolved transmission X-ray photoelectron spectroscopy at the Swiss Light Source
Authors: Roy Kanak , Raabe Joerg , Schifferle Pascal , Finizio Simone , Kleibert Armin , van Bokhoven Jeroen A. , Artiglia Luca
Published: April 2019

The successful design, installation and operation of a high spatial resolution X-ray photoelectron spectrometer at the Swiss Light Source is presented. In this instrument, a Fresnel zone plate is used to focus an X-ray beam onto the sample and an electron analyzer positioned at 45° with respect to the incoming beam direction is used to collect photoelectrons from the backside of the sample. By raster scanning the sample, transmitted current, X-ray absorption and X-ray photoemission maps can be simultaneously acquired. This work demonstrates that chemical information can be extracted with micrometre resolution; the results suggest that a spatial resolution better than 100 nm can be achieved with this approach in future. This kind of photoelectron spectromicroscope will allow in situ measurements with high spatial resolution also under ambient pressure conditions (in the millibar range). Element-specific X-ray photoemission maps can be obtained before and while exposing the sample to gas/gas mixtures to show morphological and chemical changes of the surface.
Perdeuteration, large crystal growth and neutron data collection ofLeishmania mexicanatriose-phosphate isomerase E65Q variant
Authors: Kelpšas Vinardas , Lafumat Bénédicte , Blakeley Matthew P. , Coquelle Nicolas , Oksanen Esko , von Wachenfeldt Claes
Published: April 2019

Triose-phosphate isomerase (TIM) catalyses the interconversion of dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Two catalytic mechanisms have been proposed based on two reaction-intermediate analogues, 2-phosphoglycolate (2PG) and phosphoglycolohydroxamate (PGH), that have been used as mimics of thecis-enediol(ate) intermediate in several studies of TIM. The protonation states that are critical for the mechanistic interpretation of these structures are generally not visible in the X-ray structures. To resolve these questions, it is necessary to determine the hydrogen positions using neutron crystallography. Neutron crystallography requires large crystals and benefits from replacing all hydrogens with deuterium.Leishmania mexicanatriose-phosphate isomerase was therefore perdeuterated and large crystals with 2PG and PGH were produced. Neutron diffraction data collected from two crystals with different volumes highlighted the importance of crystal volume, as smaller crystals required longer exposures and resulted in overall worse statistics.
Chlorido(2,2′-{[2-(1-methyl-1H-imidazol-2-yl-κN3)imidazolidine-1,3-diyl-κN]bis(methylene)}bis(1-methyl-1H-imidazole-κN3))copper(II) perchlorate
Authors: Padilha Diego da Silva , Scarpellini Marciela
Published: April 2019

In the crystal structure of the title complex, [CuCl(C17H24N8)]ClO4, the copper(II) metal exhibits an N4Cl pentacoordinate environment in a distorted square-pyramidal geometry. Coordination to the metal centre occurs through the three 1-methylimidazole N atoms from the pendant groups, one amine N atom from the imidazolidine moiety and one chlorido anion. Intermolecular interactions take place at two of the 1-methyl-imidazole rings in the form of parallel-displaced π–π stacking interactions forming chains parallel to theaaxis. Three O atoms of the perchlorate anion are rotationally disordered between two orientations with occupancies of 0.5.
Crystal structure of 1,3-di-tert-butyl-2-chloro-1,3,2-diazaphosphorinane − a saturated six-membered phosphorus nitrogen heterocycle with a partially flattened chair conformation and a long PIII—Cl bond
Authors: Mecke Erik , Frank Walter
Published: April 2019

Colourless blocks of 1,3-di-tert-butyl-2-chloro-1,3,2-diazaphosphorinane, C11H24ClN2P (1), were obtained by sublimationin vacuoslightly above room temperature. The asymmetric unit of the monoclinic crystal structure of the six-memberedN-heterocyclic compound is defined by one molecule in a general position. The six-membered ring of the molecule adopts a cyclohexane-like chair conformation; the chair at one side is to some extent flattened as a result of the approximately trigonal–planar coordination of both nitrogen atoms. In detail, this modified chair conformation is characterized by an angle of 53.07 (15)° between the plane defined by the three carbon atoms and the best plane of the two nitrogen atoms and the two carbon atoms bound to them, and an angle of 27.96 (7)° between the latter plane and the plane defined by the nitrogen and phosphorus atoms. Thetert-butyl groups are oriented equatorially and the chloro substituent is oriented axially. The P—Cl bond length of 2.2869 (6) Å is substantially longer than the P—Cl single-bond length in PCl3[2.034 Å; Galy & Enjalbert (1982).J. Solid State Chem.44, 1–23]. Inspection of the intermolecular distances gives no evidence for interactions stronger than van der Waals forces. The closest contact is between the Cl atom and a methylene group of a neighbouring molecule with a Cl...C distance of 3.7134 (18) Å, excluding a significant influence on the P—Cl bonding.