bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of a 14-day modified quadruple therapy containing amoxicillin, tetracycline and high dose metronidazole and proton-pump inhibitors as an empirical third line helicobacter pylori eradication treatment in Taiwan
Authors: Huang Hsiang Tso , Liang Chih-Ming , Lee Chen-Hsiang , Tai Wei-Chen , Wu Cheng-Kun , Yang Shih-Cheng , Huang Chih-Fang , Chiu Chien-Hua , Tsai Kai-Lung , Chang Meng-wei , Wang Hsin-Ming , Wu Keng-Liang , Hsu Ping-I , Wu Deng-Chyang , Chuah Seng-Kee ,   on behalf of Taiwan Acid-Related Disease (TARD) Study Group
Published: May 2018

AbstractThe antibiotics resistances to amoxicilln, tetracycline was low in Taiwan even after multiple H. pylori treatment failures and high dose metronidazole could overcome antibiotics resistance. In real world practice, susceptibility-guided treatments are not widely available. Therefore, we assessed the efficacy of 14-day modified quadruple therapy containing amoxicillin, tetracycline and high dose metronidazole and PPI as an empirical third-line rescue H. pylori treatment. This study was conducted by analyzing 70 consecutive prospectively registered patients who failed two times H. pylori eradication. All of them received endoscopy for H. pylori culture. Seven patients were lost to follow up. They were then treated according to the antibiotic susceptibility testing reports (Cultured group, n=39). Those who failed H. pylori culture were prescribed with a modified 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily and metronidazole 500 mg three times daily (empirical group, n=24). Follow-up urea breath test was performed 8 weeks later. The eradication rates attained by Cultured group and empirical group were 89.7% (95% confidence interval [CI] = 72.72%-97.11%) and 58.3% (95% CI=36.61%-77.86%), in the per protocol analysis (p=0.004); 81.4%(95% CI=66.60%-91.61%) and 51.8% (95% CI=31.9%-71.29%), in the intention-to-treat analysis (p=0.014). Culture-guided therapy was the clinical factors influencing the efficacy of H. pylori eradication (OR: 0.16; 95% CI: 0.04-0.60, p=0.006). In conclusion, empirical 14-day modified 3 quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment arobably but the success rate of the third-line susceptibility-guided treatment was only moderate (<90%).
TLR3-TRIF pathway activation by Neospora caninum RNA enhances infection control
Authors: Miranda Vanessa dos Santos , França Flávia Batista Ferreira , da Costa Mylla Spirandelli , Silva Vanessa Resende Souza , Mota Caroline Martins , Barros Patrício da Silva Cardoso , Parreira Kleber Simônio , Santiago Fernanda Maria , Mineo Jose Roberto , Mineo Tiago Wilson Patriarca 
Published: May 2018

AbstractNeospora caninum is a protozoan parasite closely related to Toxoplasma gondii and has been studied for causing neuromuscular disease in dogs and abortions in cattle. It is recognized as the major cause of economic losses in bovine products. In that sense, this study aimed to evaluate the role of TLR3-TRIF dependent resistance against N. caninum infection. We observed that TLR3−/− and TRIF−/− mice presented higher parasite burden, increased inflammatory lesions and reduced production of IL-12p40, TNF, IFN-γ, and NO. Differently from T. gondii, N. caninum tachyzoites and its RNA recruited TLR3 and IRF3 to the parasitophorous vacuole (PV). We observed that N. caninum upregulated the expression of TRIF in macrophages, which by its turn upregulated IFN-α and IFN-β in the presence of the parasite. Furthermore, TRIF−/− infected macrophages produced lower levels of IL-12p40 and IFN-α replacement was able to completely restore the production of this key cytokine. Our results have shown that TLR3-TRIF signaling pathway enhances resistance against N. caninum infection, since it improves Th1 immune responses that control parasitism and tissue inflammation, which are hallmarks of the disease.
Marine sponges as Chloroflexi hot-spots: Genomic insights and high resolution visualization of an abundant and diverse symbiotic clade
Authors: Bayer Kristina , Jahn Martin T. , Slaby Beate M. , Moitinho-Silva Lucas , Hentschel Ute 
Published: May 2018

AbstractChloroflexirepresent a widespread, yet enigmatic bacterial phylum. Meta-and single cell genomics were performed to shed light on the functional gene repertoire ofChloroflexisymbionts from the HMA spongeAplysina aerophoba. Eighteen draft genomes were reconstructed and placed into phylogenetic context of which six were investigated in detail. Common genomic features ofChloroflexisponge symbionts were related to central energy and carbon converting pathways, amino acid and fatty acid metabolism and respiration. Clade specific metabolic features included a massively expanded genomic repertoire for carbohydrate degradation in Anaerolineae and Caldilineae genomes, and amino acid utilization as nutrient source by SAR202. While Anaerolineae and Caldilineae import cofactors and vitamins, SAR202 genomes harbor genes encoding for co-factor biosynthesis. A number of features relevant to symbiosis were further identified, including CRISPRs-Cas systems, eukaryote-like repeat proteins and secondary metabolite gene clusters.Chloroflexisymbionts were visualized in the sponge extracellular matrix at ultrastructural resolution by FISH-CLEM method.Chloroflexicells were generally rod-shaped and about 1 μm in length, albeit displayed different and characteristic cellular morphotypes per each class. The extensive potential for carbohydrate degradation has been reported previously forCa. Poribacteria and SAUL, typical symbionts of HMA sponges, and we propose here that HMA sponge symbionts collectively engage in degradation of dissolved organic matter, both labile and recalcitrant. Thus sponge microbes may not only provide nutrients to the sponge host, but also contribute to DOM re-cycling and primary productivity in reef ecosystems via a pathway termed the “sponge loop”.
Phenotypic and metabolic plasticity shapes life-history strategies under combinations of abiotic stresses
Authors: Shaar-Moshe Lidor , Hayouka Ruchama , Roessner Ute , Peleg Zvi 
Published: May 2018

AbstractPlants developed various reversible and non-reversible acclimation mechanisms to cope with the multifaceted nature of abiotic stress combinations. We hypothesized that in order to endure these stress combinations, plants elicit distinctive acclimation strategies through specific trade-offs between reproduction and defense. To investigateBrachypodium distachyonacclimation strategies to combinations of salinity, drought and heat, we applied a system biology approach, integrating physiological, metabolic and transcriptional analyses. We analyzed the trade-offs among functional and performance traits, and their effects on plant fitness. A combination of drought and heat resulted in escape strategy, while under a combination of salinity and heat, plants exhibited avoidance strategy. On the other hand, under combinations of salinity and drought, with or without heat stress, plant fitness (i.e. germination rate of subsequent generation) was severely impaired. These results indicate that under combined stresses, plants’ life-history strategies were shaped by the limits of phenotypic and metabolic plasticity and the trade-offs between traits, thereby giving raise to distinct acclimations. Our findings provide a mechanistic understanding of plant acclimations to combinations of abiotic stresses and shed light on the different life-history strategies that can contribute to grass fitness and possibly to their dispersion under changing environments.
Isotropic myosin-generated tissue tension is required for the dynamic orientation of the mitotic spindle
Authors: Lam Maxine SY , Lisica Ana , Ramkumar Nitya , Mao Yanlan , Charras Guillaume , Baum Buzz 
Published: May 2018

ABSTRACTThe ability of epithelial cells to divide along their long cell axis, known as “Hertwig’s rule”, has been proposed to play an important and wide-ranging role in homogenising epithelial cell packing during tissue development and homeostasis. Since the position of the anaphase spindle defines the division plane, how divisions are oriented requires an understanding of the mechanisms that position the mitotic spindle. While many of the molecules required to orient the mitotic spindle have been identified in genetic screens, the mechanisms by which spindles read and align with the long cell axis remain poorly understood. Here, in exploring the dynamics of spindle orientation in mechanically distinct regions of the fly notum, we find that the ability of cells to properly orient their divisions depends both on cortical cues and on local tissue tension. Thus, spindles align with the long cell axis in tissues in which isotropic tension is elevated, but fail to do so in elongated cells within the crowded midline, where tension is low. Importantly, these region-specific differences in spindle behaviour can be reversed by decreasing or increasing the activity of non-muscle Myosin II. In addition, spindles in a tissue experiencing isotropic stress fail to align with the long cell axis if cells are mechanically isolated from their neighbours. These data lead us to propose that isotropic tension is required within an epithelium to provide cells with a mechanically stable substrate upon which localised cortical Dynein can pull on astral microtubules to orient the spindle.
Strange Stable Replicators Generated From Mumps Virus cDNA Clones
Authors: Bamford Connor , Wignall-Fleming Elizabeth , Randall Richard , Duprex Paul , Rima Bert 
Published: May 2018

AbstractIn reverse genetic experiments we have isolated recombinant mumps viruses (rMuV) based on a recent clinical isolate that carry large numbers of mutations clustered in small parts of their genome and which are not caused by biased hyper-mutation. In two separate experiments we obtained such rMuV: one virus had 19 mutations in the V/P region of the genome; the other, which also contained an extra transcription unit encoding green fluorescent protein (EGFP), had 32 mutations in the N gene. These specific constellations of mutations have not been observed in naturally occurring MuV isolates. The vast majority of the mutations (48/51) are synonymous.On passage in Vero cells and human B-LCL cells, a B lymphocyte-like cell Line, these mutations appear stable as no reversal occurs to the original consensus sequences, though mutations in other genes occur and change in frequency during passage. Defective Interfering RNAs accumulate in passage in Vero cells but not in B-LCL cells. Interestingly, in all passaged samples the level of variation in the EGFP gene is the same as in the viral genes, though it is unlikely that this gene is under any functionality constraint. The stability in repeated high multiplicity passage indicates that the constellation of mutations is placing the virus on a fitness peak from which it cannot escape. What mechanism gave rise to these mutant viruses and their stability remain open questions of interest to a wider field than mumps reverse genetics alone.
Generation of light-producing somatic-transgenic mice using adeno-associated virus vectors
Authors: Karda Rajvinder , Rahim Ahad A. , Wong Andrew M.S. , Suff Natalie , Antinao Diaz Juan , Perocheau Dany P. , Palomar Martin Nuria , Hughes Michael , Delhove Juliette M.K.M. , Counsell John R. , Cooper Jonathan D. , Henckaerts Els , Mckay Tristan R. , Buckley Suzanne M.K. , Waddington Simon N. 
Published: May 2018

AbstractWe have previously designed a library of lentiviral vectors to generate somatic-transgenic rodents to monitor signalling pathways in diseased organs using whole-body bioluminescence imaging, in conscious, freely moving rodents. We have now expanded this technology to adeno-associated viral vectors. We first explored bio-distribution by assessing GFP expression after neonatal intravenous delivery of AAV8. We observed widespread gene expression in, central and peripheral nervous system, liver, kidney and skeletal muscle. Next, we selected a constitutive SFFV promoter and NFκB binding sequence for bioluminescence and biosensor evaluation.An intravenous injection of AAV8 containing firefly luciferase and eGFP under transcriptional control of either element resulted in strong and persistent widespread luciferase expression. A single dose of LPS-induced a 10-fold increase in luciferase expression in AAV8-NFκB mice and immunohistochemistry revealed GFP expression in cells of astrocytic and neuronal morphology. Importantly, whole-body bioluminescence persisted up to 240 days.To further restrict biosensor activity to the CNS, we performed intracerebroventricular injection of each vector. We observed greater restriction of bioluminescence to the head and spine with both vectors. Immunohistochemistry revealed strongest expression in cells of neuronal morphology. LPS administration stimulated a 4-fold increase over baseline bioluminescence.We have validated a novel biosensor technology in an AAV system by using an NFκB response element and revealed its potential to monitor signalling pathway in a non-invasive manner using a model of LPS-induced inflammation. This technology employs the 3R’s of biomedical animal research, complements existing germline-transgenic models and may be applicable to other rodent disease models with the use of different response elements.
Theoretical Tool Bridging Cell Polarities with Development of Robust Morphologies
Authors: Nissen Silas Boye , Rønhild Steven , Trusina Ala , Sneppen Kim 
Published: May 2018

ABSTRACTDespite continual renewal and damages, a multicellular organism is able to maintain its complex morphology. How is this stability compatible with the complexity and diversity of living forms? Looking for answers at protein level may be limiting as diverging protein sequences can result in similar morphologies. Inspired by the progressive role of apical-basal and planar cell polarity in development, we propose that stability, complexity, and diversity are emergent properties in populations of proliferating polarized cells. We support our hypothesis by a theoretical approach, developed to effectively capture both types of polar cell adhesions. When applied to specific cases of development gastrulation and the origins of folds and tubes our theoretical tool suggests experimentally testable predictions pointing to the strength of polar adhesion, restricted directions of cell polarities, and the rate of cell proliferation to be major determinants of morphological diversity and stability.
Reciprocal Modulation Between Amyloid Precursor Protein and Synaptic Membrane Cholesterol Revealed By Live Cell Imaging
Authors: DelBove Claire E. , Strothman Claire E. , Lazarenko Roman M. , Huang Hui , Sanders Charles R. , Zhang Qi 
Published: May 2018

SummaryThe amyloid precursor protein (APP) has been extensively studied because of its association with Alzheimer’s disease (AD). However, APP distribution across different subcellular membrane compartments and its function in neurons remains unclear. We generated an APP fusion protein with a pH-sensitive green fluorescent protein at its ectodomain and a pH-insensitive blue fluorescent protein at its cytosolic domain and used it to measure APP’s distribution, subcellular trafficking and cleavage in live neurons. This reporter, closely resembling endogenous APP, revealed only a limited correlation between synaptic activities and APP trafficking. However, the synaptic surface distribution of APP was inversely correlated to membrane cholesterol levels, a phenomenon that involves APP’s cholesterol-binding site. Mutations within this site not only altered surface APP and cholesterol levels in a dominant negative manner, but also increased synaptic vulnerability to moderate membrane cholesterol reduction. Our results reveal reciprocal modulation of APP and membrane cholesterol levels at synaptic boutons.
Tendon slack length is the primary determinant of plantarflexor muscle-tendon function in computational simulations of gait
Authors: Baxter Josh R. , Hast Michael W. 
Published: May 2018

1AbstractBackground: Locomotion is partly dictated by plantarflexor function and structure. Computational simulations are powerful tools capable of testing the isolated effects of muscle-tendon structure on gait function.Research Question: The purpose of this study was to characterize the sensitivity of plantarflexor muscle function based on muscle-tendon unit (MTU) parameters. We hypothesized that plantarflexor metabolics and shortening dynamics would be sensitive to MTU parameters.Methods: Stance phase of gait was simulated using a musculoskeletal model and computed muscle control algorithm. Optimal muscle fiber length, tendon slack length, and tendon stiffness parameters were systematically changed to test the effects on plantarflexor metabolics and shortening dynamics.Results and Significance: Plantarflexor metabolic demands were 8 and 28 times more sensitive to muscle fiber and tendon slack lengths, respectively, compared to the effect of tendon stiffness. Shortened tendon slack lengths induced a large passive plantarflexion moment during early stance, which required non-physiologic dorsiflexor contractions. Conversely, longer muscle fiber and tendon slack lengths increased the shortening demands of the plantarflexors to account for the added length of the MTU. These findings highlight the importance of carefully selecting MTU parameters when modeling gait with musculoskeletal models, especially in pathologic or high-performance athlete populations.
The Roles of Different Spatial Frequency Channels in Real-World Visual Motion Perception
Authors: Shi Cong , Pundlik Shrinivas , Luo Gang 
Published: May 2018

AbstractSpeed perception is an important task performed by our visual system in various daily life tasks. In various psychophysical tests, relationship between spatial frequency, temporal frequency, and speed has been examined in human subjects. The role of vision impairment in speed perception has also been previously examined. In this work, we examine the inter-relationship between speed, spatial frequency, low vision conditions, and the type of input motion stimuli in motion perception accuracy. For this purpose, we propose a computational model for speed perception and evaluate it in custom generated natural and stochastic sequences by simulating low-vision conditions (low pass filtering at different cutoff frequencies) as well as complementary vision conditions (high pass versions at the same cutoff frequencies). Our results show that low frequency components are critical for accurate speed perception, whereas high frequencies do not play any important role in speed estimation. Since perception of low frequencies may not be impaired in visual acuity loss, speed perception was not found to be impaired in low vision conditions compared to normal vision condition. We also report significant differences between natural and stochastic stimuli, notably an increase in speed estimation error when using stochastic stimuli compared to natural sequences, emphasizing the use of natural stimuli when performing future psychophysical studies for speed perception.
A Generative Bayesian Approach for Incorporating Biosurveillance Sources into Epidemiological Models
Authors: Manheim David 
Published: May 2018

AbstractBiosurveillance “systematically collects and analyzes data for the purpose of detecting cases of disease, [and] outbreaks of disease.” (Wagner, Moore and Aryel, 2006) This typically involves using a set of known sources of epidemiological data, instead of opportunistically using the data sources which become available over time. This work attempts to partially remedy that limitation by using an easily adapted generative Bayesian econometric model to allow incorporation of novel data sources. This is done by building a generative model of the information sources, then using Bayesian Markov-chain Monte-Carlo to find the relationships between data and actual caseloads to use in an epidemiological model1.While the application presented is limited to three data sources for a single disease (influenza), the methodology is potentially widely applicable, and enables rapid incorporation of a variety of sources and source types.
Biophysical Principles of Lineage Factor PU.1 Binding Revealed by NextPBMs
Authors: Mohaghegh Nima , Bray David , Keenan Jessica , Penvose Ashley , Andrilenas Kellen K. , Ramlall Vijendra , Siggers Trevor 
Published: May 2018

ABSTRACTDetermining the biophysical principles that shape transcription factor (TF) binding in a cell-specific manner is key to quantitative models of gene expression. High-throughput (HT)in vitromethods measuring protein-DNA binding are invaluable for relating TF binding affinity to genome-wide binding; however, the impact of cell-specific post-translational modifications (PTMs) and cofactors are not routinely assessed. To address these limitations, we describe a new HT approach, called nextPBMs (nuclearextractprotein-bindingmicroarrays), to characterize TF binding that accounts for PTMs and endogenous cofactors. We use nextPBMs to examine the DNA binding of the lineage factor PU.1/Spi1 and IRF8 in human monocytes. We identify two binding modes for PU.1 in monocytes – autonomous binding unaffected by PTMs and cooperative binding with IRF8, and identify a single cooperative mode for IRF8. We characterize the DNA binding of PU.1:IRF8 complexes, and show how nextPBMs can be used to discover cell-specific cofactors and characterize TF cooperativity at single-nucleotide resolution. We show that chromatin state and cofactors both influence the affinity requirements for PU.1 binding sites. Furthermore, we find that the influences of cooperative (IRF8) and collaborative (C/EBPα) cofactors on PU.1-binding-site affinity are independent and additive.
A Deep Learning Approach for Learning Intrinsic Protein-RNA Binding Preferences
Authors: Ben-Bassat Ilan , Chor Benny , Orenstein Yaron 
Published: May 2018

AbstractMotivationThe complexes formed by binding of proteins to RNAs play key roles in many biological processes, such as splicing, gene expression regulation, translation, and viral replication. Understanding protein-RNA binding may thus provide important insights to the functionality and dynamics of many cellular processes. This has sparked substantial interest in exploring protein-RNA binding experimentally, and predicting it computationally. The key computational challenge is to efficiently and accurately infer RNA-binding models that will enable prediction of novel protein-RNA interactions to additional transcripts of interest.ResultsWe developed DLPRB, a new deep neural network (DNN) approach for learning protein-RNA binding preferences and predicting novel interactions. We present two different network architectures: a convolutional neural network (CNN), and a recurrent neural network (RNN). The novelty of our network hinges upon two key aspects: (i) the joint analysis of both RNA sequence and structure, which is represented as a probability vector of different RNA structural contexts; (ii) novel features in the architecture of the networks, such as the application of RNNs to RNA-binding prediction, and the combination of hundreds of variable-length filters in the CNN. Our results in inferring accurate RNA-binding models from high-throughput in vitro data exhibit substantial improvements, compared to all previous approaches for protein-RNA binding prediction (both DNN and non-DNN based). A highly significant improvement is achieved for in vitro binding prediction, and a more modest, yet statistically significant,improvement for in vivo binding prediction. When incorporating experimentally-measured RNA structure compared to predicted one, the improvement on in vivo data increases. By visualizing the binding specificities, we can gain novel biological insights underlying the mechanism of protein RNA-binding.AvailabilityThe source code is publicly available at https://github.com/ilanbb/dlprb.Contactyaronore@bgu.ac.ilSupplementary informationSupplementary data are available at Bioinformatics online.