bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mangrove vegetation inspires a new approach to protect shorelines
Authors: Segmaier Robert , Staggs Stephanie , Palmer Sarah 
Published: August 2018

I. AbstractMangroves are found worldwide across the rivers and coastlines in tropical regions. They are robust against storm surges and tsunamic for a long time. The roots have the most contributions for their resiliency and therefore can be inspired for future manmade structures. The motion of water in riverine mangrove forest is expected to be impacted by mangrove roots, which in turn disturb the transport of nutrients, contaminants, and residues in these systems. In this paper, a facile method for protecting shoreline is described and review and the significant impact of this method were reviewed. Bioinspired simplified models as and obstruction to water currents in shorelines, and coastal areas are presented. It was found that Mangrove roots produce complex flow structure interactions with their environment, which affect the nutrient, habitat and aquatic animals. Analysis of the flow structure behind the roots extend to a broad range of mangrove-inspired applications and provide understandings into flows that are more complex and more indicative of the flows encountered in the unidirectional riverine flow.
Calicivirus VP2 forms a portal to mediate endosome escape
Authors: Conley Michaela , McElwee Marion , Azmi Liyana , Gabrielsen Mads , Byron Olwyn , Goodfellow Ian G. , Bhella David 
Published: August 2018

AbstractTo initiate the infectious process, many viruses enter their host cells by triggering endocytosis following receptor engagement. The mechanism by which non-enveloped viruses, such as the caliciviruses, escape the endosome is however poorly understood. TheCaliciviridaeinclude many important human and animal pathogens, most notably norovirus, the cause of winter vomiting disease. Here we show that VP2, a minor capsid protein encoded by all caliciviruses, forms a large portal assembly at a unique three-fold symmetry axis following receptor engagement. This feature surrounds an open pore in the capsid shell. We hypothesise that the VP2 portal complex is the means by which the virus escapes the endosome, pene-trating the endosomal membrane to release the viral genome into the cytoplasm. Cryogenic electron microscopy (cryoEM) and asymmetric reconstruction were used to investigate structural changes in the capsid of feline calicivirus (FCV) that occur when the virus binds to its cellular receptor junctional adhesion molecule-A (fJAM-A). Near atomic-resolution structures were calculated for the native virion alone and decorated with soluble receptor fragments. We present atomic models of the major capsid protein VP1 in the presence and absence of fJAM-A, revealing the contact interface and conformational changes brought about by the interaction. Furthermore, we have calculated an atomic model of the portal protein VP2 and revealed the structural changes in VP1 that lead to pore formation. While VP2 was known to be critical for the production of infectious virus, its function has been hitherto undetermined. Our finding that VP2 assembles a portal that is likely responsible for endosome escape represents a major step forward in our understanding of both theCaliciviridaeand icosahedral RNA containing viruses in general.
DeepCAPE: a deep convolutional neural network for the accurate prediction of enhancers
Authors: Chen Shengquan , Gan Mingxin , Lv Hairong , Jiang Rui 
Published: August 2018

AbstractThe establishment of a landscape of enhancers across human cells is crucial to deciphering the mechanism of gene regulation, cell differentiation, and disease development. High-throughput experimental approaches, though having successfully reported enhancers in typical cell lines, are still too costly and time consuming to perform systematic identification of enhancers specific to different cell lines under a variety of disease status. Existing computational methods, though capable of predicting regulatory elements purely relying on DNA sequences, lack the power of cell line-specific screening. Recent studies have suggested that chromatin accessibility of a DNA segment is closely related to its potential function in regulation, and thus may provide useful information in identifying regulatory elements. Motivated by the above understanding, we integrate DNA sequences and chromatin accessibility data to accurately predict enhancers in a cell line-specific manner. We proposed DeepCAPE, a deep convolutional neural network to predict enhancers via the integration of DNA sequences and DNase-seq data. We demonstrate that our model not only consistently outperforms existing methods in the classification of enhancers against background sequences, but also accurately predicts enhancers across different cell lines. We further visualize kernels of the first convolutional layer and show the match of identified sequence signatures and known motifs. We finally demonstrate the potential ability of our model to explain functional implications of putative disease-associated genetic variants and discriminate disease-related enhancers.
Multiple Exposures, Reinfection, and Risk of Progression to Active Tuberculosis
Authors: Ackley Sarah F. , Lee Robyn S. , Worden Lee , Zwick Erin , Porco Travis C. , Behr Marcel A. , Pepperell Caitlin S. 
Published: August 2018

AbstractA recent study reported on a tuberculosis outbreak in a largely Inuit village. Among recently infected individuals, exposure to additional active cases was associated with an increasing probability of developing active disease within a year. Using binomial risk models, we evaluated two potential mechanisms by which multiple infections during the first year following initial infection could account for increasing disease risk with increasing exposures. In the reinfection model, multiple exposures have an independent risk of becoming an infection, and infections contribute independently to active disease. In the threshold model, disease risk follows a sigmoidal function with small numbers of exposures conferring a low risk of active disease and large numbers of exposures conferring a high risk. To determine the dynamic impact of reinfection during the early phase of infection, we performed simulations from a modified Reed-Frost model of TB dynamics following spread from an initial number of cases. We parameterized this model with the maximum likelihood estimates from the reinfection and threshold models in addition to the observed distribution of exposures among recent infections. We find that both models can plausibly account for the observed increase in disease risk with increasing exposures, but the threshold model confers a better fit than a nested model without a threshold (p=0.04). Our simulations indicate that multiple exposures during this critical time period can lead to dramatic increases in outbreak size. In order to decrease TB burden in high-prevalence settings, it may be necessary to implement measures aimed at preventing repeated exposures, in addition to preventing primary infection.
An open-source control system for in vivo fluorescence measurements from deep-brain structures
Authors: Owen Scott F. , Kreitzer Anatol C. 
Published: August 2018

ABSTRACTBackgroundIntracranial photometry through chronically implanted optical fibers is a widely adopted technique for measuring signals from fluorescent probes in deep-brain structures. The recent proliferation of bright, photo-stable, and specific genetically-encoded fluorescent reporters for calcium and for other neuromodulators has greatly increased the utility and popularity of this technique.New MethodHere we describe an open-source, cost-effective, microcontroller-based solution for controlling optical components in an intracranial photometry system and processing the resulting signal.ResultsWe show proof-of-principle that this system supports high quality intracranial photometry recordings from dorsal striatum in freely moving mice. A single system supports simultaneous fluorescence measurements in two independent color channels, but multiple systems can be integrated together if additional fluorescence channels are required. This system is designed to work in combination with either commercially available or custom-built optical components. Parts can be purchased for less than one tenth the cost of commercially available alternatives and complete assembly takes less than one day for an inexperienced user.Comparison with Existing Method(s)Currently available hardware draws on a variety of commercial, custom-built, or hybrid elements for both optical and electronic components. Many of these hardware systems are either specialized and inflexible, or over-engineered and expensive.ConclusionsThis open-source system increases experimental flexibility while reducing cost relative to current commercially available components. All software and firmware are open-source and customizable, affording a degree of experimental flexibility that is not available in current commercial systems.
Pairwise Efficiency: A new mathematical approach to qPCR data analysis increases the precision of the classical calibration curve assay
Authors: Panina Yulia , Germond Arno , David Brit G. , Watanabe Tomonobu M. ,   Laboratory for Comprehensive Bioimaging, RIKEN Center for Biosystems Dynamics Research(BDR)
Published: August 2018

ABSTRACTThe real-time quantitative polymerase chain reaction (qPCR) is routinely used for quantification of nucleic acids and is considered the gold standard in the field of relative nucleic acid measurements. The efficiency of the qPCR reaction is one of the most important parameters that needs to be determined, reported, and incorporated into data analysis in any qPCR experiment. The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines recognize the calibration curve as the method of choice for estimation of qPCR efficiency. The precision of this method has been reported to be between SD=0.007 (3 replicates) and SD=0.022 (no replicates). In this manuscript we present a novel approach to analysing qPCR data obtained by running a dilution series. Unlike previously developed methods, our method relies on a new formula that describes pairwise relationships between data points on separate amplification curves and thus operates extensive statistics (hundreds of estimations). The comparison of our method with classical calibration curve by Monte Carlo simulation shows that our approach can almost double the precision of efficiency and gene expression ratio estimations on the same dataset.
Genomic signatures of sympatric speciation with historical and contemporary gene flow in a tropical anthozoan
Authors: Titus Benjamin M. , Blischak Paul D. , Daly Marymegan 
Published: August 2018

AbstractSympatric diversification is increasingly thought to have played an important role in the evolution of biodiversity around the globe. However, an in situ sympatric origin for co-distributed taxa is difficult to demonstrate empirically because different evolutionary processes can lead to similar biogeographic outcomes-especially in ecosystems with few hard barriers to dispersal that can facilitate allopatric speciation followed by secondary contact (e.g. marine habitats). Here we use a genomic (ddRADseq), model-based approach to delimit a cryptic species complex of tropical sea anemones that are co-distributed on coral reefs throughout the Tropical Western Atlantic. We use coalescent simulations in fastsimcoal2 to test competing diversification scenarios that span the allopatric-sympatric continuum. We recover support that the corkscrew sea anemone Bartholomea annulata (Le Sueur, 1817) is a cryptic species complex, co-distributed throughout its range. Simulation and model selection analyses suggest these lineages arose in the face of historical and contemporary gene flow, supporting a sympatric origin, but an alternative secondary contact model also receives appreciable model support. Leveraging the genome of Exaiptasia pallida we identify five loci under divergent selection between cryptic B. annulata lineages that fall within mRNA transcripts or CDS regions. Our study provides a rare empirical, genomic example of sympatric speciation in a tropical anthozoan-a group that includes reef-building corals. Finally, these data represent the first range-wide molecular study of any tropical sea anemone, underscoring that anemone diversity is under described in the tropics, and highlighting the need for additional systematic studies into these ecologically and economically important species.
Eukaryotic Acquisition of a Bacterial Operon
Authors: Kominek Jacek , Doering Drew T. , Opulente Dana A. , Shen Xing-Xing , Zhou Xiaofan , De Virgilio Jeremy , Hulfachor Amanda B. , Kurtzman Cletus P. , Rokas Antonis , Hittinger Chris Todd 
Published: August 2018

AbstractOperons are a hallmark of bacterial genomes, where they allow concerted expression of multiple functionally related genes as single polycistronic transcripts. They are rare in eukaryotes, where each gene usually drives expression of its own independent messenger RNAs. Here we report the horizontal operon transfer of a catecholate-class siderophore biosynthesis pathway from Enterobacteriaceae into a group of closely related yeast taxa. We further show that the co-linearly arranged secondary metabolism genes are actively expressed, exhibit mainly eukaryotic transcriptional features, and enable the sequestration and uptake of iron. After transfer to the eukaryotic host, several genetic changes occurred, including the acquisition of polyadenylation sites, structural rearrangements, integration of eukaryotic genes, and secondary loss in some lineages. We conclude that the operon genes were likely captured in the shared insect gut habitat, modified for eukaryotic gene expression, and maintained by selection to adapt to the highly-competitive, iron-limited environment.
HDAC Inhibitors Rescue Multiple Disease-Causing CFTR Variants
Authors: Anglès Frédéric , Hutt Darren M. , Balch William E. 
Published: August 2018

AbstractUnderstanding the role of the epigenome in protein misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable respond of the disease population to any therapeutic. An ever-growing body of evidence has shown that histone deacetylase (HDAC) inhibitors (HDACi) can have significant benefit in correcting protein misfolding diseases that occur in response to both familial and somatic mutation. Cystic fibrosis (CF) is a familial autosomal recessive disease, caused by genetic diversity in the CF transmembrane conductance regulator (CFTR) gene, a cAMP-dependent chloride channel expressed at the apical plasma membrane of epithelial cells in multiple tissues. The potential utility of HDACi in correcting F508del as well as the over 2000 CF-associated variants remains controversial. To address this concern, we examined the impact of FDA-approved HDACi on the trafficking and function of a panel of CFTR variants. Our data reveal that panobinostat (LBH-589) and romidepsin (FK-228) provide functional correction of class II and III CFTR variants, restoring cell surface chloride channel activity in primary human bronchial epithelial (hBE) cells. We further demonstrate a synergistic effect of these HDACi with Vx809, that together can significantly restore channel activity for multiple CFTR variants. These data suggest that HDACi can serve to level the cellular playing field for correcting CF-causing mutations, a leveling effect that might also extend to other protein misfolding diseases.
Chronotopic Maps in Human Medial Premotor Cortex
Authors: Protopapa Foteini , Hayashi Masamichi J. , Kulashekhar Shrikanth , der Zwaag Wietske van , Battistella Giovanni , Murray Micah M. , Kanai Ryota , Bueti Domenica 
Published: August 2018

AbstractTime is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultra-high-field 7-Tesla functional magnetic resonance imaging, we show that in the medial premotor cortex of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface, so as to form chronomaps. The response of each portion in a chronomap is enhanced by preferred and neighboring durations and suppressed by non-preferred durations represented in distant portions of the map. These findings identify duration-sensitive tuning as a neural mechanism underlying the recognition of time and demonstrate for the first time that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.
EGFR Signalling Coordinates Patterning with Cell Survival DuringDrosophilaEpidermal Development
Authors: Crossman Samuel H. , Streichan Sebastian J. , Vincent Jean-Paul 
Published: August 2018

AbstractExtensive apoptosis is often seen in patterning mutants, suggesting that tissues can detect and eliminate potentially harmful mis-specified cells. Here we show that the pattern of apoptosis in the embryonic epidermis ofDrosophilais not a response to fate mis-specification but can instead be explained by the limiting availability of pro-survival signalling molecules released from locations determined by patterning information. In wild type embryos, the segmentation cascade elicits the segmental production of several EGFR ligands, including the TGF-alpha, Spitz and the Neuregulin, Vein. This leads to an undulating pattern of signalling activity, which prevents expression of the pro-apoptotic genehidthroughout the epidermis. In segmentation mutants, where specific peaks of EGFR ligands fail to form, gaps in signalling activity appear, leading to coincidenthidupregulation and subsequent cell death. These data provide a mechanistic understanding of how cell survival, and thus appropriate tissue size, is made contingent on correct patterning.
miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2
Authors: Leigh Wesley , Liu Zhenxing , Nian Xiaoge , Zhang Yong 
Published: August 2018

AbstractCircadian clocks control the timing of animal behavior rhythms to anticipate daily environmental changes. Fruit flies gradually increase their activity and reach a peak of activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210KO) exhibit a dramatic phase advance of evening anticipatory behavior about 2 hours. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3’ UTR of Fas2 (Fas2ΔmiR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO and Fas2ΔmiR-210. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior.Author summaryCircadian clocks control the timing of animal physiology. Drosophila has been a powerful model in understanding the mechanisms of circadian regulation. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. Here we identify miR-210 as a critical regulator of evening anticipatory behavior. Depletion of miR-210 in flies advances evening anticipation. Futhermore, we identify the cell adhesion molecular Fas2 as miR-210’s target in circadian regulation. Fas2 abundance is increased in fly brain lacking of miR-210. Using CRISPR-Cas9 genome editing method, we deleted the miR-210 binding site on 3’ untranslated region of Fas2 and observed similar phenotype as miR-210 mutants. Altogether, our results indicate a novel mechanism of miR-210 in regulation of circadian anticipatory behavior through inhibition of Fas2.
Therapeutic effects of favipiravir against severe fever with thrombocytopenia syndrome virus infection in a lethal mouse model: dose-efficacy studies upon oral administration
Authors: Tani Hideki , Komeno Takashi , Fukuma Aiko , Fukushi Shuetsu , Taniguchi Satoshi , Shimojima Masayuki , Uda Akihiko , Morikawa Shigeru , Nakajima Nozomi , Furuta Yousuke , Saijo Masayuki 
Published: August 2018

AbstractBackgroundSevere fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is a viral hemorrhagic fever with a high case fatality rate. Favipiravir was reported to be effective in the treatment of SFTSV infection in vivo in type I interferon receptor knockout (IFNAR-/-) mice at treatment dosages of both 60 mg/kg/day and 300 mg/kg/day for a duration of 5 days.MethodsIn this study, the efficacy of favipiravir at dosages of 120 mg/kg/day and 200 mg/kg/day against SFTSV infection in an IFNAR-/- mouse infection model was investigated. IFNAR-/- mice were subcutaneously infected with SFTSV at a 1.0 × 106 50% tissue culture infectious dose followed by twice daily administration of favipiravir, comprising a total dose of either 120 mg/kg/day or 200 mg/kg/day. The treatment was initiated either immediately post infection or at predesignated time points post infection.ResultsAll mice treated with favipiravir at dosages of 120 mg/kg/day or 200 mg/kg/day survived when the treatment was initiated at no later than 4 days post infection. A decrease in body weight of mice was observed when the treatment was initiated at 3–4 days post infection. Furthermore, all control mice died. The body weight of mice did not decrease when treatment with favipiravir was initiated immediately post infection at dosages of 120 mg/kg/day and 200 mg/kg/day.ConclusionsSimilar to the literature-reported peritoneal administration of favipiravir at 300 mg/kg/day, the oral administration of favipiravir at dosages of 120 mg/kg/day and 200 mg/kg/day to IFNAR-/- mice infected with SFTSV was effective.Author summarySevere fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a generalized infectious disease with a high case fatality rate. Currently, no effective therapeutics for SFTS is available; therefore, the development of effective antiviral drugs is needed. Favipiravir exhibits antiviral activity against various RNA viruses, including SFTSV. The present study demonstrated the efficacy of favipiravir in the treatment of SFTSV infection in a lethal mouse model, when the dose was set similar to that approved for anti-influenza drug in humans by the Ministry of Health, Labour and Welfare, Japan. The present study suggests that favipiravir is a promising drug for the treatment of SFTSV infection.