bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposed U.S. regulation of gene-edited food animals is not fit for purpose
Authors: Van Eenennaam Alison L. , Wells Kevin D. , Murray James D. 
Published: March 2019

AbstractDietary DNA is generally regarded as safe to consume, and is a routine ingredient of food obtained from any living organism. Millions of naturally-occurring DNA variations are observed when comparing the genomic sequence of any two healthy individuals of a given species. Breeders routinely select desired traits resulting from this DNA variation to develop new cultivars and varieties of food plants and animals. Regulatory agencies do not evaluate these new varieties prior to commercial release. Gene editing tools now allow plant and animal breeders to precisely introduce useful genetic variation into agricultural breeding programs. The U.S. Department of Agriculture (USDA) announced that it has no plans to place additional regulations on gene-edited plants that could otherwise have been developed through traditional breeding prior to commercialization. However, the U.S. Food and Drug Administration (FDA) has proposed mandatory premarket new animal drug regulatory evaluation for all food animals whose genomes have been intentionally altered using modern molecular technologies including gene editing technologies. This runs counter to U.S. biotechnology policy that regulatory oversight should be triggered by unreasonable risk, and not by the fact that an organism has been modified by a particular process or technique. Breeder intention is not associated with product risk. Harmonizing the regulations associated with gene editing in food species is imperative to allow both plant and animal breeders access to gene editing tools to introduce useful sustainability traits like disease resistance, climate adaptability, and food quality attributes into U.S. agricultural breeding programs.
Remote preparation for single-photon two-qubit hybrid state with hyperentanglement via linear-optical elements
Authors: Jiao Xian-Fang , Zhou Ping , Lv Shu-Xin , Wang Zhi-Yong 
Published: March 2019

AbstractLinear-optical-based quantum information processing has attached much attention since photon is an ideal medium for transmitting quantum information remotely. Until now, there are some important works in quantum state remote preparation, the method for reconstructing quantum state deterministically via linear optics. However, most of the methods are protocols to prepare single-qubit states remotely via linear-optical elements. In this article, we investigate the methods to prepare two-qubit hybrid states remotely. We present a deterministic remote state preparation scheme for an arbitrary two-qubit hybrid state via a hyperentangled Bell state, resorting to linear-optical elements only. The sender rotates the spatial-mode state and polarization state of the hyperentangled photon respectively in accordance with his knowledge of the two-qubit hybrid state, and the receiver can reconstruct the original two-qubit hybrid state by applying appropriate recovery operations. Moreover, we discuss the remote state preparation scheme for the two-qubit hybrid state via partially hyperentangled Bell state.
Interaction between active particles and quantum vortices leading to Kelvin wave generation
Authors: Giuriato Umberto , Krstulovic Giorgio 
Published: March 2019

AbstractOne of the main features of superfluids is the presence of topological defects with quantised circulation. These objects are known as quantum vortices and exhibit a hydrodynamic behaviour. Nowadays, particles are the main experimental tool used to visualise quantum vortices and to study their dynamics. We use a self-consistent model based on the three-dimensional Gross-Pitaevskii (GP) equation to explore theoretically and numerically the attractive interaction between particles and quantized vortices at very low temperature. Particles are described as localised potentials depleting the superfluid and following Newtonian dynamics. We are able to derive analytically a reduced central-force model that only depends on the classical degrees of freedom of the particle. Such model is found to be consistent with the GP simulations. We then generalised the model to include deformations of the vortex filament. The resulting long-range mutual interaction qualitatively reproduces the observed generation of a cusp on the vortex filament during the particle approach. Moreover, we show that particles can excite Kelvin waves on the vortex filament through a resonance mechanism even if they are still far from it.
Pitx2 cholinergic interneurons are the source of C bouton synapses on brainstem motor neurons
Authors: Rozani Ismini , Tsapara Georgia , Witts Emily C. , Deaville S. James , Miles Gareth B. , Zagoraiou Laskaro 
Published: March 2019

AbstractCholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, as revealed by studies of large cholinergic synapses on spinal motor neurons, called C boutons, which seem to control motor neuron excitability in a task-dependent manner. C boutons on spinal motor neurons stem from spinal interneurons that express the transcription factor Pitx2. C boutons have also been identified on the motor neurons of specific cranial nuclei. However, the source and roles of cranial C boutons are less clear. Previous studies suggest that they originate from Pitx2+ and Pitx2− neurons, in contrast to spinal cord C boutons that originate solely from Pitx2 neurons. Here, we address this controversy using mouse genetics, and demonstrate that brainstem C boutons are Pitx2+ derived. We also identify new Pitx2 populations and map the cholinergic Pitx2 neurons of the mouse brain. Taken together, our data present important new information about the anatomical organization of cholinergic systems which impact motor systems of the brainstem. These findings will enable further analyses of the specific roles of cholinergic modulation in motor control.
Influence of Different Urban Structures on Metal Contamination in Two Metropolitan Cities
Authors: Alharbi Badr H. , Pasha Mohammad J. , Al-Shamsi Mohammed Ahmad S. 
Published: March 2019

AbstractThe influence of urban structures and land use patterns of metropolitan cities on the distribution of contaminants is not well understood. In this study, two metropolitan cities [Jeddah (a typical corridor city) and Madinah (a typical compact city)], featuring different spreading patterns and urban structures, were selected to investigate the contamination level and potential risk caused by metals (i.e., Pb, Zn, Co, Fe, Al, Cr, Cu, Ni, and Mn) associated with urban dust. The findings of this study show that a metropolitan city with a limited variety of activities and a polar center (e.g., Madinah) displays a typical distribution pattern of metals, i.e., concentrations of metals increase gradually toward the center of the city. In contrast, a metropolitan city with multiple major activities (e.g., Jeddah) displays a different distribution pattern, controlled by multiple key actors (e.g., seaports, oil refineries, and desalination/power plants) able to shift the location of highest contamination away from the city center. The above findings are supported by the results of several contamination and health indices. In Jeddah, the highest Pb contamination was found near an oil refinery based on geoaccumulation index (Igeo), contamination factor (CF), enrichment factor (EF), and ecological risk (Ei) values; whereas, the highest Zn contamination was found near a seaport, based on EF, CF, and Ei values. However, in Madinah, the contamination indices indicate that the most contaminated locations are near the city center. The highest non-carcinogenic health risk in Jeddah was found near an oil refinery and in the city center; whereas in Madinah, it was found mainly in the city center. Although there is no significant risk of cancer due to metals associated with dust in the two cities, Cr, representing a health risk contribution of >24%, was the major contributor of non-carcinogenic health risk in the two metropolitan cities.
Transcriptome analysis of rumen epithelium and meta-transcriptome analysis of rumen epimural microbial community in young calves with feed induced acidosis
Authors: Li Wenli , Gelsinger Sonia , Edwards Andrea , Riehle Christina , Koch Daniel 
Published: March 2019

AbstractMany common management practices used to raise dairy calves while on milk and during weaning can cause rumen acidosis. Ruminal pH has long been used to identify ruminal acidosis. However, few attempts were undertaken to understand the role of prolonged ruminal acidosis on rumen microbial community or host health in young calves long after weaning. Thus, the molecular changes associated with prolonged rumen acidosis in post weaning young calves are largely unknown. In this study, we induced ruminal acidosis by feeding a highly processed, starch-rich diet to calves starting from one week of age through 16 weeks. Rumen epithelial tissues were collected at necropsy at 17 weeks of age. Transcriptome analyses on the rumen epithelium and meta-transcriptome analysis of rumen epimural microbial communities were carried out. Calves with induced ruminal acidosis showed significantly less weight gain over the course of the experiment, in addition to substantially lower ruminal pH in comparison to the control group. For rumen epithelial transcriptome, a total of 672 genes (fold-change, FC ≥ 1.5; adjusted-p≤ 0.05) showed significant differential expression in comparison to control. Biological pathways impacted by these differentially expressed genes included cell signaling and morphogenesis, indicating the impact of ruminal acidosis on rumen epithelium development. rRNA read-based microbial classification indicated significant increase in abundance of several genera in calves with induced acidosis. Our study provides insight into host rumen transcriptome changes associated with prolonged acidosis in post weaning calves. Shifts in microbial species abundance are promising for microbial species-based biomarker development and artificial manipulation. Such knowledge provides a foundation for future more precise diagnosis and preventative management of rumen acidosis in dairy calves.
Genetic differences in host infectivity affect disease spread and survival in epidemics
Authors: Anacleto Osvaldo , Cabaleiro Santiago , Villanueva Beatriz , Saura María , Houston Ross D. , Woolliams John A. , Doeschl-Wilson Andrea B. 
Published: March 2019

AbstractSurvival during an epidemic is partly determined by host genetics. While quantitative genetic studies typically consider survival as an indicator for disease resistance (an individual’s propensity to avoid becoming infected or diseased), mortality rates of populations undergoing an epidemic are also affected by endurance (the propensity of diseased individual to survive the infection) and infectivity (i.e. the propensity of an infected individual to transmit disease). Few studies have demonstrated genetic variation in disease endurance, and no study has demonstrated genetic variation in host infectivity, despite strong evidence for considerable phenotypic variation in this trait. Here we propose an experimental design and statistical models for estimating genetic diversity in all three host traits. Using an infection model in fish we provide, for the first time, direct evidence for genetic variation in host infectivity, in addition to variation in resistance and endurance. We also demonstrate how genetic differences in these three traits contribute to survival. Our results imply that animals can evolve different disease response types affecting epidemic survival rates, with important implications for understanding and controlling epidemics.
Glucose tolerance in Canadian and French cystic fibrosis adult patients
Authors: Reynaud Quitterie , Boudreau Valérie , Touzet Sandrine , Desjardins Katherine , Bourdy Stéphanie Poupon , Blond Emilie , Berthiaume Yves , Rabasa-Lhoret Rémi , Durieu Isabelle 
Published: March 2019

AbstractCystic fibrosis (CF)-related diabetes is associated with increased mortality. We analysed the clinical and glycemic profiles of two cohorts of patients treated according to the same guidelines in France and Canada. To investigate incidence differences in phenotypic and glucose abnormalities and to explore the evolution over a 4-year follow-up period, two cohorts of 224 Canadian and 147 French adult CF patients (≥18 years) without treated CF-related diabetes (CFRD) were followed over a 4 year period. In each of these groups, we investigated the longitudinal relationship between glucose tolerance and pulmonary function. An annual 2-hour oral glucose tolerance test was performed: fasting blood glucose (G0) and 2-h blood glucose (G2) were measured. Patients were classified at inclusion according to their glucose tolerance status: Normal glucose tolerant, abnormal glucose tolerant or de novo CFRD. Age, sex ratio and proportion of F508del homozygous patients were not statistically different between both cohorts. Canadian patients had better pulmonary function (median %FEV1 (IQR): 71.0 (55.0–82.0) vs. 64.0 (40.0–78.0), p < 0.001) and greater body mass index (BMI; median BMI in kg/m2) (IQR) 21.1 (19.5–22.8) vs. 19.9 (18.4–21.4), p < 0.001). Glucose values: G0 (5.4 (5.0–5.9) vs. 4.8 (4.5–5.1) mmol/L, p < 0.001) and G2 (7.6 (5.8–9.7) vs. 6.5 (5.2–8.5) mmol/L, p = 0.001) were higher in the Canadian cohort translating into a higher incidence of de novo CFRD diagnosis (19.2 vs. 9.8%, p = 0.003). Decline in FEV1 over time was not different between patients according to glucose tolerance groups. Despite higher glucose levels and incidence of de novo CFRD, Canadian CF patients have a better lung function and a higher BMI than French patients. In spite of these differences between the cohorts, the decline in FEV1 in patients with abnormal glucose tolerance is similar between these groups.
Inhibition of PGE2/EP4 receptor signaling enhances oxaliplatin efficacy in resistant colon cancer cells through modulation of oxidative stress
Authors: Huang Huakang , Aladelokun Oladimeji , Ideta Takayasu , Giardina Charles , Ellis Lee M. , Rosenberg Daniel W. 
Published: March 2019

AbstractThe platinum-based chemotherapeutic agent, oxaliplatin, is used to treat advanced colorectal cancer (CRC). Unfortunately, nearly all patients acquire resistance to oxaliplatin after long-term use, limiting its therapeutic efficacy. Since COX-2 and PGE2 signaling can impact colon cancer cell proliferation and survival, we examined how this pathway was affected in an oxaliplatin resistant colon cancer cell line. PGE2 levels were significantly elevated in oxaliplatin-resistant HT29 cells (OXR) compared to naïve parental HT29 cells (PAR). This increase was associated with elevated COX-2 (17.9-fold; P = 0.008) and reduced 15-hydroxyprostaglandin dehydrogenase (2.9-fold; P < 0.0001) expression. RNAi knockdown of microsomal prostaglandin E synthase-1, the rate-limiting enzyme in PGE2 synthesis, sensitized OXR cells to oxaliplatin. Downstream effects of PGE2 in OXR cells were also examined. Selective inhibition of the EP4 PGE2 receptor by the small molecule inhibitor, L-161,982 enhanced oxaliplatin-induced apoptosis in OXR cells. L-161,982 also reduced expression of the colonic stem cell markers, CD133 and CD44, and inhibited tumor sphere formation. The accumulation of intracellular reactive oxygen species (ROS), a key component of oxaliplatin cytotoxicity, was significantly increased by EP4 inhibition (2.4 -fold; P < 0.0001). Overall, our findings uncover an important role for the COX-2/PGE2/EP4 signaling axis in oxaliplatin resistance via regulation of oxidative stress.
Extensive epigenetic and transcriptomic variability between genetically identical human B-lymphoblastoid cells with implications in pharmacogenomics research
Authors: Ozgyin Lilla , Horvath Attila , Hevessy Zsuzsanna , Balint Balint L. 
Published: March 2019

AbstractGenotyped human B-lymphoblastoid cell lines (LCLs) are widely used models in mapping quantitative trait loci for chromatin features, gene expression, and drug response. The extent of genotype-independent functional genomic variability of the LCL model, although largely overlooked, may inform association study design. In this study, we use flow cytometry, chromatin immunoprecipitation sequencing and mRNA sequencing to study surface marker patterns, quantify genome-wide chromatin changes (H3K27ac) and transcriptome variability, respectively, among five isogenic LCLs derived from the same individual. Most of the studied LCLs were non-monoclonal and had mature B cell phenotypes. Strikingly, nearly one-fourth of active gene regulatory regions showed significantly variable H3K27ac levels, especially enhancers, among which several were classified as clustered enhancers. Large, contiguous genomic regions showed signs of coordinated activity change. Regulatory differences were mirrored by mRNA expression changes, preferentially affecting hundreds of genes involved in specialized cellular processes including immune and drug response pathways. Differential expression of DPYD, an enzyme involved in 5-fluorouracil (5-FU) catabolism, was associated with variable LCL growth inhibition mediated by 5-FU. The extent of genotype-independent functional genomic variability might highlight the need to revisit study design strategies for LCLs in pharmacogenomics.
Automated segmentation of the corneal endothelium in a large set of ‘real-world’ specular microscopy images using the U-Net architecture
Authors: Daniel Moritz C. , Atzrodt Lisa , Bucher Felicitas , Wacker Katrin , Böhringer Stefan , Reinhard Thomas , Böhringer Daniel 
Published: March 2019

AbstractMonitoring the density of corneal endothelial cells (CEC) is essential in the management of corneal diseases. Its manual calculation is time consuming and prone to errors. U-Net, a neural network for biomedical image segmentation, has shown promising results in the automated segmentation of images of healthy corneas and good quality. The purpose of this study was to assess its performance in “real-world” CEC images (variable quality, different ophthalmologic diseases). The outcome measures were: precision and recall of the extraction of CEC, correctness of CEC density estimation, detection of ungradable images. A classical approach based on grayscale morphology and water shedding was pursued for comparison. There was good agreement between the automated image analysis and the manual annotation from the U-Net. R-square from Pearson’s correlation was 0.96. Recall of CEC averaged 0.34 and precision 0.84. The U-Net correctly predicted the CEC density in a large set of images of healthy and diseased corneas, including images of poor quality. It robustly ignored image regions with poor visibility of CEC. The classical approach, however, did not provide acceptable results. R-square from Pearson’s correlation with the ground truth was as low as 0.35.
Differential gene expression in response to eCry3.1Ab ingestion in an unselected and eCry3.1Ab-selected western corn rootworm (Diabrotica virgifera virgifera LeConte) population
Authors: Zhao Zixiao , Meihls Lisa N. , Hibbard Bruce E. , Ji Tieming , Elsik Christine G. , Shelby Kent S. 
Published: March 2019

AbstractDiabrotica virgifera virgifera LeConte, the western corn rootworm (WCR) is one of the most destructive pests in the U.S. Corn Belt. Transgenic maize lines expressing various Cry toxins from Bacillus thuringiensis have been adopted as a management strategy. However, resistance to many Bt toxins has occurred. To investigate the mechanisms of Bt resistance we carried out RNA-seq using Illumina sequencing technology on resistant, eCry3.1Ab-selected and susceptible, unselected, whole WCR neonates which fed on seedling maize with and without eCry3.1Ab for 12 and 24 hours. In a parallel experiment RNA-seq experiments were conducted when only the midgut of neonate WCR was evaluated from the same treatments. After de novo transcriptome assembly we identified differentially expressed genes (DEGs). Results from the assemblies and annotation indicate that WCR neonates from the eCry3.1Ab-selected resistant colony expressed a small number of up and down-regulated genes following Bt intoxication. In contrast, unselected susceptible WCR neonates expressed a large number of up and down-regulated transcripts in response to intoxication. Annotation and pathway analysis of DEGs between susceptible and resistant whole WCR and their midgut tissue revealed genes associated with cell membrane, immune response, detoxification, and potential Bt receptors which are likely related to eCry3.1Ab resistance. This research provides a framework to study the toxicology of Bt toxins and mechanism of resistance in WCR, an economically important coleopteran pest species.
mtDNA analysis confirms the endangered Kashmir musk deer extends its range to Nepal
Authors: Singh Paras Bikram , Khatiwada Janak Raj , Saud Pradip , Jiang Zhigang 
Published: March 2019

AbstractMusk deerMoschusspp. are endemic to the high mountain forests of central Asia. The taxonomic status of musk deer in the central and western Himalayas is poorly understood. We investigated the phylogenetic relationship of musk deer from the central and western Himalayas based on mitochondrial genomic data of Cytochrome b (380 bps) and D-loop (1000 bps). Our results distinguished two divergent lineages using higher bootstrap support (bs) values from the Maximum likelihood and Bayesian posterior probabilities (bpp). Both the Manang and Kaski lineages from central Nepal are confirmed as Himalayan musk deerMoschus leucogasterand represent a species complex widespread throughout the central and eastern Himalayan region. The musk deer Mustang lineage was confirmed as Kashmir musk deerMoschus cupreusand has wide distribution in the western Himalayas (from central Nepal to Afghanistan). Our analysis validates that Kashmir musk deer is a genetically distinct species and it clarifies that Himalayan musk deer and Kashmir musk deer are confirmed instead of Alpine musk deerMoschus chrysogasterwhich has been previously described from the southern parts of Himalayas of Nepal, India and Pakistan.
Epitope mapping of diverse influenza Hemagglutinin drug candidates using HDX-MS
Authors: Puchades Cristina , Kűkrer Başak , Diefenbach Otto , Sneekes-Vriese Eveline , Juraszek Jarek , Koudstaal Wouter , Apetri Adrian 
Published: March 2019

AbstractEpitope characterization is critical for elucidating the mechanism of action of drug candidates. However, traditional high-resolution epitope mapping techniques are not well suited for screening numerous drug candidates recognizing a similar target. Here, we use Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) to explore the conformational impact of diverse drug molecules binding on Hemagglutinin (HA), the major surface antigen of influenza viruses. We optimized a semi-automated HDX-MS workflow to systematically probe distantly related HA subtypes in complex with 4 different drug candidates, ranging from a monoclonal antibody to a small synthetic peptide. This fast, cost-effective HDX-MS epitope mapping approach accurately determined the main antigenic site in all cases. Moreover, our studies reveal distinct changes in the local conformational dynamics of HA associated to the molecular mechanism of neutralization, establishing a marker for broad anti-HA activity. Taken together, these findings highlight the potential for HDX-MS epitope mapping-based screening to identify promising candidates against HA at early stages of drug discovery.