bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assortative mating in hybrid zones is remarkably ineffective in promoting speciation
Authors: Irwin Darren E. 
Published: May 2019

AbstractAssortative mating and other forms of partial prezygotic isolation are often viewed as being more important than partial postzygotic isolation (low fitness of hybrids) early in the process of speciation. Here I simulate secondary contact between two populations (‘species’) to examine effects of pre- and postzygotic isolation in preventing blending. A small reduction in hybrid fitness (e.g., 10%) produces a narrower hybrid zone than a strong but imperfect mating preference (e.g., 10x stronger preference for conspecific over heterospecific mates). This is because, in the latter case, rare F1 hybrids find each other attractive (due to assortative mating), leading to the gradual buildup of a full continuum of intermediates between the two species. The cline is narrower than would result from purely neutral diffusion over the same number of generations, largely due to the frequency-dependent mating disadvantage of individuals of rare mating types. Hybrids tend to pay this cost of rarity more than pure individuals, meaning there is an induced postzygotic isolation effect of assortative mating. These results prompt a questioning of the concept of partial prezygotic isolation, since it is not very isolating unless there is also postzygotic isolation.
Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Authors: Hu Ying , Ranganathan Mohini , Shu Chang , Liang Xiaoyu , Ganesh Suhas , Yan Chunhua , Zhang Xinyu , Aouizerat Bradley E , Krystal John H , D’Souza Deepak C. , Xu Ke 
Published: May 2019

AbstractDelta 9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is also known to modulate immune response in peripheral cells. The mechanisms of THC’s effects on gene expression in human immune cells remains poorly understood. Combining a within-subject design with single cell transcriptome mapping, we report that administration of THC acutely alters gene expression in 15,973 human blood immune cells. Controlled for high inter-individual transcriptomic variability, we identified 294 transcriptome-wide significant genes among eight cell types including 69 common genes and 225 cell-type specific genes affected by acute THC administration, including those genes involving not only in immune response, cytokine production, but signal transduction, and cell proliferation and apoptosis. We revealed distinct transcriptomic sub-clusters affected by THC in major immune cell types where THC perturbed cell type-specific intracellular gene expression correlations. Gene set enrichment analysis further supports the findings of THC’s common and cell-type specific effects on immune response and cell toxicity. We found that THC alters the correlation of cannabinoid receptor gene, CNR2, with other genes in B cells, in which CNR2 showed the highest level of expression. This comprehensive cell-specific transcriptomic profiling identified novel genes regulated by THC and provides important insights into THC’s acute effects on immune function that may have important medical implications.
Resolving the 3D landscape of transcription-linked mammalian chromatin folding
Authors: Hsieh Tsung-Han S. , Slobodyanyuk Elena , Hansen Anders S. , Cattoglio Claudia , Rando Oliver J. , Tjian Robert , Darzacq Xavier 
Published: May 2019

ABSTRACTChromatin folding below the scale of topologically associating domains (TADs) remains largely unexplored in mammals. Here, we used a high-resolution 3C-based method, Micro-C, to probe links between 3D-genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregate TAD regions into “microTADs” with distinct regulatory features. Enhancer-promoter and promoter-promoter interactions extending from the edge of these domains predominantly link co-regulated loci, often independently of CTCF/Cohesin. Acute inhibition of transcription disrupts the gene-related folding features without altering higher-order chromatin structures. Intriguingly, we detect “two-start” zig-zag 30-nanometer chromatin fibers. Our work uncovers the finer-scale genome organization that establishes novel functional links between chromatin folding and gene regulation.ONE SENTENCE SUMMARYTranscriptional regulatory elements shape 3D genome architecture of microTADs.
Hygiene Hampers Competitive Release of Resistant Bacteria in the Commensal Microbiota
Authors: Aspenberg Magnus , Sasane Sara Maad , Nilsson Fredrik , Brown Sam P. , Waldetoft Kristofer Wollein 
Published: May 2019

AbstractGood hygiene, in both health care and the community, is central to containing the rise of antibiotic resistance, as well as to infection control more generally. But despite the well-known importance, the ecological mechanisms by which hygiene affects resistance evolution remain obscure. Using metacommunity ecology theory, we here propose that hygiene attenuates the effect of antibiotic selection pressure. Specifically, we predict that hygiene limits the scope for antibiotics to induce competitive release of resistant bacteria within treated hosts, and that this is due to a modulating effect of hygiene on the distribution of resistant and sensitive strains in the host population. We show this in a mathematical model of bacterial metacommunity dynamics, and test the results against data on antibiotic resistance, antibiotic treatment, and the use of alcohol-based hand rub in long-term care facilities. Our results underscore the importance of hygiene, and point to a concrete way to weaken the link between antibiotic use and increasing resistance.
Complex evolutionary origins of specialized metabolite gene cluster diversity among the plant pathogenic fungi of theFusarium graminearumspecies complex
Authors: Tralamazza Sabina Moser , Rocha Liliana Oliveira , Oggenfuss Ursula , Corrêa Benedito , Croll Daniel 
Published: May 2019

AbstractFungal genomes encode highly organized gene clusters that underlie the production of specialized (or secondary) metabolites. Gene clusters encode key functions to exploit plant hosts or environmental niches. Promiscuous exchange among species and frequent reconfigurations make gene clusters some of the most dynamic elements of fungal genomes. Despite evidence for high diversity in gene cluster content among closely related strains, the microevolutionary processes driving gene cluster gain, loss and neofunctionalization are largely unknown. We analyzed theFusarium graminearumspecies complex (FGSC) composed of plant pathogens producing potent mycotoxins and causing Fusarium head blight on cereals. Wede novoassembled genomes of previously uncharacterized FGSC members (two strains ofF. austroamericanum,F. cortaderiaeandF. meridionale). Our analyses of eight species of the FGSC in addition to 15 otherFusariumspecies identified a pangenome of 54 gene clusters within FGSC. We found that multiple independent losses were a key factor generating extant cluster diversity within the FGSC and theFusariumgenus. We identified a modular gene cluster conserved among distantly related fungi, which was likely reconfigured to encode different functions. We also found strong evidence that a rare cluster in FGSC was gained through an ancient horizontal transfer between bacteria and fungi. Chromosomal rearrangements underlying cluster loss were often complex and were likely facilitated by an enrichment in specific transposable elements. Our findings identify important transitory stages in the birth and death process of specialized metabolism gene clusters among very closely related species.
New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells
Authors: Ghandhi Shanaz A. , Shuryak Igor , Morton Shad R. , Amundson Sally A. , Brenner David J. 
Published: May 2019

AbstractIn the event of a nuclear attack or radiation event, there would be an urgent need for assessing and reconstructing the dose to which hundreds or thousands of individuals were exposed. These measurements would need a rapid assay to facilitate triage and medical management for individuals based on dose. Our approaches to development of rapid assays for reconstructing dose, using transcriptomics, have led to identification of gene sets that have potential to be used in the field; but need further testing. This was a proof-of-principle study for new methods using radiation-responsive genes to generate quantitative, rather than categorical, radiation-dose reconstructions based on a blood sample. We used a new normalization method to reduce effects of variability of gene signals in unirradiated samples across studies; developed a quantitative dose-reconstruction method that is generally under-utilized compared to categorical methods; and combined these to determine a gene-set as a reconstructor. Our dose-reconstruction biomarker was trained on two data sets and tested on two independent ones. It was able to predict dose up to 4.5 Gy with root mean squared error (RMSE) of ± 0.35 Gy on test datasets (same platform), and up to 6.0 Gy with RMSE of 1.74 Gy on another (different platform).
Getting Beyond Interruptive Alerts: Reducing Unintentional Duplicate Orders using a Visual Aid
Authors: Horng Steven , Joseph Joshua W , Calder Shelley , Stevens Jennifer P , O’Donoghue Ashley L , Safran Charles , Nathanson Larry A , Leventhal Evan L 
Published: May 2019

ABSTRACTImportanceElectronic health records (EHRs) allow teams of clinicians to simultaneously care for patients but an unintended consequence could result in duplicate ordering of tests and medications.ObjectiveWe asked if a simple visual aid would reduce duplicate ordering of tests and medications for busy teams of clinicians in our emergency department by placing a red highlight around the checkbox of a computer-based order if previously ordered.DesignWe performed an interrupted time series to analyze all patient visits 1 year before and 1 year after the intervention. Significance testing was performed using a negative binomial regression with Newey-West standard errors, correcting for patient level variables and environmental variables that might be associated with duplicate orders.SettingThe emergency department of an academic hospital in Boston, MA with 55,000 visits annually.Participants184,722 consecutive emergency department patients.ExposureIf an order had previously been placed during that ED visit, we cue the user by showing a red highlight around the checkbox of that order.Main OutcomeNumber of unintentional duplicate orders.ResultsAfter deployment of the non-interrupting nudge, the rate of unintentional duplicates for laboratory orders decreased 49% (incidence rate ratio 0.51, 95% CI 0.45-0.59) and for radiology orders decreased with an incidence rate ratio of 0.60 (0.44-0.82). There was no change in unintentional medication duplicate orders. We estimated that the nudge eliminated 17,936 clicks in our EHR.Conclusions and RelevancePassive visual queues that provide just-in-time decision support are effective, not disruptive of workflow, and may decrease alert fatigue in busy clinical environments.Key PointsQuestionCan a simple visual aid reduce duplicate ordering in an electronic health record?FindingsIn this interrupted time series, the rate of unintentional duplicates for laboratory orders decreased 49% and for radiology orders decreased 40%. There was no change in unintentional medication duplicate orders. We estimated that the nudge eliminated 17,936 clicks in our EHR.MeaningQuality improvement often relies on changing clinician behavior. We believe guiding clinicians to a right action is better than telling the clinician they have already made an error. Our approach will help reduce alert fatigue and lessen clinician complaints about EHRs.
Programmatic goals and spatial epidemiology influence the merit of targeted versus of population-wide interventions for yaws eradication
Authors: Mooring Eric Q. , Marks Michael , Mitjà Oriol , Castro Marcia , Lipsitch Marc , Murray Megan B. 
Published: May 2019

AbstractInfectious disease eradication programs often pursue spatially targeted interventions, but how well they perform might depend on the underlying spatial epidemiology and the specific goal of the program. We use a stochastic compartmental metapopulation model of yaws transmission to investigate how total targeted treatment (TTT) performs compared to mass drug administration (MDA) in different settings. While TTT can efficiently control the prevalence of active yaws disease, we consistently found that multiple rounds of TTT are required to match the impact of 1 round of MDA on the prevalence of latent yaws infection. When complete eradication of yaws is the goal, MDA can achieve the same result as TTT more quickly and probably at lower cost. We found that the performance of TTT is improved when there is little mixing between subpopulations and when there is spatial heterogeneity in transmissibility, but even in these settings, our model suggests that MDA will still outperform TTT.Significance StatementYaws is a neglected tropical disease that causes skin lesions. Eradicating yaws is challenging because people can be infected but not show any signs or symptoms for years. Using simulations, we found that targeting antibiotics to people with active yaws and to their neighbors is a good way to combat active yaws, but treating entire populations is a better way to get rid of all infections, including the hidden ones. Also, targeted treatment works better in populations in which people do not move around much and in which how easily the disease is transmitted varies from place to place. Overall, a targeted treatment strategy uses fewer antibiotics but takes longer than mass treatment to achieve results.
Hairpin: a tool for predicting structural non-coding RNA genes ad initio
Authors: Pettersen Jakob Peder 
Published: May 2019

AbstractBackgroundStructural RNA genes play important and various roles in gene expression and its regulation. Finding such RNA genes in a genome poses a challenge, which in most cases is solved by homology approaches. Ab intio methods for prediction exist, but are not that much explored.ResultsWe introduce hairpin which identify potential structural RNA genes only based on the sequence. We use the algorithm to predict RNA genes in Escherichia coli K-12. When looking at very short regions of the genome, we do not get results differing very much from a random shuffling of the genome. However, at longer stretches it is a clear biological signal. It turns out that none of the regions predicted to code for RNA genes have such an annotation in literature.ConclusionsArbitrary DNA sequences seem to give rise to transcripts with secondary structures similar to real ncRNA. We therefore conclude that exclusively looking at secondary structure base-parings is in general a futile approach.
Characterization of Single Protein Dynamics in Cell Plasma Membrane Derived Polymer Cushioned Lipid Bilayers
Authors: Cheng (Christine) Wong Wai , Juo Jz-Yuan , Liao Yi-Hung , Cheng Ching-Ya , Lin Chih-Hsiang , Hsieh Chia-Lung 
Published: May 2019

AbstractNative cell membrane derived supported lipid bilayers (SLBs) are emerging platforms that have broad applications ranging from fundamental research to next-generation biosensors. Central to the success of the platform is proper accommodation of membrane proteins so that their dynamics and functions are preserved. Polymer cushions have been commonly employed to avoid direct contact of the bilayer membrane to the supporting substrate, and thus the mobility of transmembrane proteins is maintained. However, little is known about how the polymer cushion affects the absolute mobility of membrane molecules. Here, we characterized the dynamics of single membrane proteins in polymer-cushioned lipid bilayers derived from cell plasma membranes and investigated the effects of polymer length. Three membrane proteins of distinct structures, i.e., GPI-anchored protein, single-pass transmembrane protein CD98 heavy chain, and seven-pass transmembrane protein SSTR3, were fused with green fluorescence proteins (GFPs) and their dynamics were measured by fluorescence single-molecule tracking. An automated data acquisition was implemented to study the effects of PEG polymer length to protein dynamics with large statistics. Our data showed that increasing the PEG polymer length (molecular weight from 1,000 to 5,000) enhanced the mobile fraction of the membrane proteins. Moreover, the diffusion coefficients of transmembrane proteins were raised by increasing the polymer length, whereas the diffusion coefficient of GPI-anchored protein remained almost identical with different polymer lengths. Importantly, the diffusion coefficients of the three membrane proteins became identical (2.5 μm2/s approximately) in the cushioned membrane with the longest polymer length (molecular weight of 5,000), indicating that the SLBs were fully suspended from the substrate by the polymer cushion at the microscopic length scale. Transient confinements were observed from all three proteins, and increasing the polymer length reduced the tendency of transient confinements. The measured dynamics of membrane proteins were found to be nearly unchanged after depletion of cholesterol, suggesting that the observed immobilization and transient confinement were not due to cholesterol-enriched membrane nanodomains (lipid rafts). Our single-molecule dynamics elucidate the biophysical properties of polymer cushioned plasma membrane bilayers that are potentially useful for future developments of membrane-based biosensors and analytical assays.
Molecular and transcriptional structure of the petal and leaf circadian clock inPetunia hybrida
Authors: Terry Marta I. , Carrera-Alesina Marta , Weiss Julia , Egea-Cortines Marcos 
Published: May 2019

AbstractThe plant circadian clock coordinates environmental signals with internal processes. We characterized the genomic and transcriptomic structure of thePetunia hybridaW115 clock in leaves and petals. We found three levels of evolutionary differences. First,PSEUDO-RESPONSE REGULATORS PhPRR5a, PhPRR5b, PhPRR7a, PhPRR7b, andGIGANTEA PhGI1andPhGI2, differed in gene structure including exon number and deletions including the CCT domain of the PRR family. Second, leaves showed preferential day expression while petals tended to display night expression. Under continuous dark, most genes were delayed in leaves and petals. Importantly, photoperiod sensitivity of gene expression was tissue specific asTIMING OF CAB EXPRESSION PhNTOC1was affected in leaves but not in petals, andPhPRR5b, PhPRR7band theZEITLUPEorthologCHANEL, PhCHL, were modified in petals but not leaves. Third, we identified a strong transcriptional noise at different times of the day, and high robustness at dawn in leaves and dusk in petals, coinciding with the coordination of photosynthesis and scent emission. Our results indicate multilayered evolution of thePetuniaclock including gene structure, number of genes and transcription patterns. The major transcriptional reprogramming of the clock in petals, with night expression may be involved in controlling scent emission in the dark.HighlightThe petunia leaf circadian clock shows maxima during the day while petal clock does it during the night. Reaction to dark is organ specific.
Deterioration of dry skin in arthritis model mice via stress-induced changes in immune cells in the thymus and spleen
Authors: Goto Kenji , Hiramoto Keiichi , Takada Ion , Ooi Kazuya 
Published: May 2019

ABSTRACTSkin dryness is a characteristic of rheumatoid arthritis model mice. We previously reported that the stress hormone glucocorticoid (i.e., corticosterone) is related to the induction of dry skin in arthritic mice. However, the mechanism through which stress induces dry skin in these mice is still unclear. Therefore, in this study, we examined the relationship between stress and induction of dry skin in arthritic mice. Physical stress load in mice with DBA/1JJmsSlc collagen-induced arthritis was treated with water immersion stress, and transepidermal water loss and the expression of markers associated with allergic reactions and inflammation was evaluated. Deterioration of skin dryness was observed in stressed arthritic mice compared with that in unstressed arthritic mice. Moreover, plasma levels of interleukin-6 and corticosterone were increased in stressed arthritic mice compared with those in unstressed arthritic mice. We also observed decreased regulatory T cell numbers and increased T helper type 2 cell numbers in the thymus of stressed arthritic mice compared with those in unstressed arthritic mice. These results suggested that abnormalities in the immune system were related to deterioration of dry skin in stressed arthritic mice. Thus, reduction of stress may prevent deterioration of dry skin in mice with arthritis.
Exploring the Mechanism of Olfactory Recognition at the Initial Stage by Modeling the Emission Spectrum of Electron Transfer
Authors: Liu Shu , Fu Rao , Li Guangwu 
Published: May 2019

AbstractOlfactory sense remains elusive regarding the primary reception mechanism. Some studies suggest that olfaction is a spectral sense, the olfactory event is triggered by electron transfer (ET) across the odorants at the active sites of odorant receptors (ORs). Herein we present a Donor-Bridge-Acceptor model, proposing that the ET process can be viewed as an electron hopping from the donor molecule to the odorant molecule (Bridge), then hopping off to the acceptor molecule, making the electronic state of the odorant molecule change along with vibrations (vibronic transition). The odorant specific parameter, Huang–Rhys factor can be derived fromab initiocalculations, which make the simulation of ET spectra achievable. In this study, we revealed that the emission spectra (after Gaussian convolution) can be acted as odor characteristic spectra. Using the emission spectrum of ET, we were able to reasonably interpret the similar bitter-almond odors among hydrogen cyanide, benzaldehyde and nitrobenzene. In terms of isotope effects, we succeeded in explaining why subjects can easily distinguish cyclopentadecanone from its fully deuterated analogue cyclopentadecanone-d28 but not distinguishing acetophenone from acetophenone-d8.
Development of rice conidiation media forUstilaginoidea virens
Authors: Wang Yufu , Wang Fei , Xie Songlin , Liu Yi , Qu Jinsong , Huang Junbin , Yin Weixiao , Luo Chaoxi 
Published: May 2019

AbstractRice false smut, caused by the ascomyceteUstilaginoidea virens, is a serious disease of rice worldwide. Conidia are very important infectious propagules ofU. virens, but the ability of pathogenic isolates to produce conidia frequently decreases in culture, which influences pathogenicity testing. Here, we developed tissue media with rice leaves or panicles that stimulate conidiation ofU. virens. Generally, rice leaf media more effectively increased conidiation than panicle media, and certain non-filtered tissue media were better than their filtered counterparts. Among the tested media, the Indica rice leaf medium with 0.06 g/ml of Wanxian 98 leaf was most efficient for inducing conidiation, and it was also usable for conidiation-defective isolates. Although the conidia induced in rice tissue media were smaller, they were able to germinate on potato sucrose agar medium and infect rice normally. This method provides a foundation for the production of conidia inU. virensthat will be widely applied in the pathogenicity testing as well as in genetic analyses for false smut resistance in rice cultivars.