bluuebunny/crossref_metadata_2025_split huggingface dataset:
A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors
Authors: Averaimo Stefania , Assali Ahlem , Ros Oriol , Couvet Sandrine , Zagar Yvrick , Genescu Ioana , Rebsam Alexandra , Nicol Xavier 
Published: October 2016

AbstractThe development of neuronal circuits is controlled by guidance molecules that are hypothesized to interact with the cholesterol-enriched domains of the plasma membrane termed lipid rafts. Whether such domains enable local intracellular signalling at the submicrometre scale in developing neurons and are required for shaping the nervous system connectivity in vivo remains controversial. Here, we report a role for lipid rafts in generating domains of local cAMP signalling in axonal growth cones downstream of ephrin-A repulsive guidance cues. Ephrin-A-dependent retraction of retinal ganglion cell axons involves cAMP signalling restricted to the vicinity of lipid rafts and is independent of cAMP modulation outside of this microdomain. cAMP modulation near lipid rafts controls the pruning of ectopic axonal branches of retinal ganglion cells in vivo, a process requiring intact ephrin-A signalling. Together, our findings indicate that lipid rafts structure the subcellular organization of intracellular cAMP signalling shaping axonal arbors during the nervous system development.
Localized force application reveals mechanically sensitive domains of Piezo1
Authors: Wu Jason , Goyal Raman , Grandl Jörg 
Published: October 2016

AbstractPiezos are mechanically activated ion channels that function as sensors of touch and pressure in various cell types. However, the precise mechanism and structures mediating mechanical activation and subsequent inactivation have not yet been identified. Here we use magnetic nanoparticles as localized transducers of mechanical force in combination with pressure-clamp electrophysiology to identify mechanically sensitive domains important for activation and inactivation.
Noise reduction facilitated by dosage compensation in gene networks
Authors: Peng Weilin , Song Ruijie , Acar Murat 
Published: October 2016

AbstractGenetic noise together with genome duplication and volume changes during cell cycle are significant contributors to cell-to-cell heterogeneity. How can cells buffer the effects of these unavoidable epigenetic and genetic variations on phenotypes that are sensitive to such variations? Here we show that a simple network motif that is essential for network-dosage compensation can reduce the effects of extrinsic noise on the network output. Using natural and synthetic gene networks with and without the network motif, we measure gene network activity in single yeast cells and find that the activity of the compensated network is significantly lower in noise compared with the non-compensated network. A mathematical analysis provides intuitive insights into these results and a novel stochastic model tracking cell-volume and cell-cycle predicts the experimental results. Our work implies that noise is a selectable trait tunable by evolution.
The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is shaped by strong epistatic interactions
Authors: Jochumsen Nicholas , Marvig Rasmus L. , Damkiær Søren , Jensen Rune Lyngklip , Paulander Wilhelm , Molin Søren , Jelsbak Lars , Folkesson Anders 
Published: October 2016

AbstractColistin is an antimicrobial peptide that has become the only remaining alternative for the treatment of multidrug-resistant Gram-negative bacterial infections, but little is known of how clinical levels of colistin resistance evolve. We use in vitro experimental evolution and whole-genome sequencing of colistin-resistant Pseudomonas aeruginosa isolates from cystic fibrosis patients to reconstruct the molecular evolutionary pathways open for high-level colistin resistance. We show that the evolution of resistance is a complex, multistep process that requires mutation in at least five independent loci that synergistically create the phenotype. Strong intergenic epistasis limits the number of possible evolutionary pathways to resistance. Mutations in transcriptional regulators are essential for resistance evolution and function as nodes that potentiate further evolution towards higher resistance by functionalizing and increasing the effect of the other mutations. These results add to our understanding of clinical antimicrobial peptide resistance and the prediction of resistance evolution.
Organization of olfactory centres in the malaria mosquito Anopheles gambiae
Authors: Riabinina Olena , Task Darya , Marr Elizabeth , Lin Chun-Chieh , Alford Robert , O'Brochta David A. , Potter Christopher J. 
Published: October 2016

AbstractMosquitoes are vectors for multiple infectious human diseases and use a variety of sensory cues (olfactory, temperature, humidity and visual) to locate a human host. A comprehensive understanding of the circuitry underlying sensory signalling in the mosquito brain is lacking. Here we used the Q-system of binary gene expression to develop transgenic lines of Anopheles gambiae in which olfactory receptor neurons expressing the odorant receptor co-receptor (Orco) gene are labelled with GFP. These neurons project from the antennae and maxillary palps to the antennal lobe (AL) and from the labella on the proboscis to the suboesophageal zone (SEZ), suggesting integration of olfactory and gustatory signals occurs in this brain region. We present detailed anatomical maps of olfactory innervations in the AL and the SEZ, identifying glomeruli that may respond to human body odours or carbon dioxide. Our results pave the way for anatomical and functional neurogenetic studies of sensory processing in mosquitoes.
Large Fizeau’s light-dragging effect in a moving electromagnetically induced transparent medium
Authors: Kuan Pei-Chen , Huang Chang , Chan Wei Sheng , Kosen Sandoko , Lan Shau-Yu 
Published: October 2016

AbstractAs one of the most influential experiments on the development of modern macroscopic theory from Newtonian mechanics to Einstein’s special theory of relativity, the phenomenon of light dragging in a moving medium has been discussed and observed extensively in different types of systems. To have a significant dragging effect, the long duration of light travelling in the medium is preferred. Here we demonstrate a light-dragging experiment in an electromagnetically induced transparent cold atomic ensemble and enhance the dragging effect by at least three orders of magnitude compared with the previous experiments. With a large enhancement of the dragging effect, we realize an atom-based velocimeter that has a sensitivity two orders of magnitude higher than the velocity width of the atomic medium used. Such a demonstration could pave the way for motional sensing using the collective state of atoms in a room temperature vapour cell or solid state material.
Methylotrophic methanogenesis discovered in the archaeal phylum Verstraetearchaeota
Authors: Vanwonterghem Inka , Evans Paul N. , Parks Donovan H. , Jensen Paul D. , Woodcroft Ben J. , Hugenholtz Philip , Tyson Gene W. 
Published: October 2016

AbstractMethanogenesis is the primary biogenic source of methane in the atmosphere and a key contributor to climate change. The long-standing dogma that methanogenesis originated within the Euryarchaeota was recently challenged by the discovery of putative methane-metabolizing genes in members of the Bathyarchaeota, suggesting that methanogenesis may be more phylogenetically widespread than currently appreciated. Here, we present the discovery of divergent methyl-coenzyme M reductase genes in population genomes recovered from anoxic environments with high methane flux that belong to a new archaeal phylum, the Verstraetearchaeota. These archaea encode the genes required for methylotrophic methanogenesis, and may conserve energy using a mechanism similar to that proposed for the obligate H2-dependent methylotrophic Methanomassiliicoccales and recently described Candidatus ‘Methanofastidiosa’. Our findings indicate that we are only beginning to understand methanogen diversity and support an ancient origin for methane metabolism in the Archaea, which is changing our understanding of the global carbon cycle.
Neural Activities Underlying the Feedback Express Salience Prediction Errors for Appetitive and Aversive Stimuli
Authors: Gu Yan , Hu Xueping , Pan Weigang , Yang Chun , Wang Lijun , Li Yiyuan , Chen Antao 
Published: October 2016

AbstractFeedback information is essential for us to adapt appropriately to the environment. The feedback-related negativity (FRN), a frontocentral negative deflection after the delivery of feedback, has been found to be larger for outcomes that are worse than expected and it reflects a reward prediction error derived from the midbrain dopaminergic projections to the anterior cingulate cortex (ACC), as stated in reinforcement learning theory. In contrast, the prediction of response-outcome (PRO) model claims that the neural activity in the mediofrontal cortex (mPFC), especially the ACC, is sensitive to the violation of expectancy, irrespective of the valence of feedback. Additionally, increasing evidence has demonstrated significant activities in the striatum, anterior insula and occipital lobe for unexpected outcomes independently of their valence. Thus, the neural mechanism of the feedback remains under dispute. Here, we investigated the feedback with monetary reward and electrical pain shock in one task via functional magnetic resonance imaging. The results revealed significant prediction-error-related activities in the bilateral fusiform gyrus, right middle frontal gyrus and left cingulate gyrus for both money and pain. This implies that some regions underlying the feedback may signal a salience prediction error rather than a reward prediction error.
Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats
Authors: Dai Die , Gao Yiqiao , Chen Jiaqing , Huang Yin , Zhang Zunjian , Xu Fengguo 
Published: October 2016

AbstractLipopolysaccharide (LPS) can lead to uncontrollable cytokine production and eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has been widely reported. In our study we observed that two thirds of the rats (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking the dynamic metabolic change in survival and non-survival rats in the early stage may reveal new system information to understand the inter-individual variation in response to LPS. As the time-resolved datasets are very complex and no single method can elucidate the problem clearly and comprehensively, the static and dynamic metabolomics methods were employed in combination as cross-validation. Intriguingly, some common results have been observed. Lipids were the main different metabolites between survival and non-survival rats in pre-dose serum and in the early stage of infection with LPS. The LPS treatment led to S-adenosly-methionine and total cysteine individual difference in early stage, and subsequent significant perturbations in energy metabolism and oxidative stress. Furthermore, cytokine profiles were analyzed to identify potential biological associations between cytokines and specific metabolites. Our collective findings may provide some heuristic guidance for elucidating the underlying mechanism of individual difference in LPS-mediated disease.
Lamb-dip spectroscopy of the C−N stretching band of methylamine by using frequency-tunable microwave sidebands of CO2 laser lines
Authors: Sun Zhen-Dong , Qi Shan-Dong , Lees Ronald M. , Xu Li-Hong 
Published: October 2016

AbstractLamb-dip spectroscopy of the C−N stretching band of methylamine has been systematically extended to P-, Q-, and R-branch by using microwave sidebands of a large number of CO2 laser lines as frequency-tunable infrared sources in a sub-Doppler spectrometer. Lamb-dip signals of more than 150 spectral lines have been observed with a resolution of 0.4 MHz and their frequencies have been precisely measured with an accuracy of ±0.1 MHz. More than 30 closed combination loops have been formed, which unambiguously confirm the assignments. For over 150 vibrational excited levels in 27 substates, refined term values have been determined and expanded in J(J + 1) power-series to determine the substate origins and the effective rotational constants. For transitions with Aa torsion-inversion symmetry in torsional state υt = 0, 57 K-doublet lines displaying asymmetry splittings have been observed and the splitting constants for levels with K = 1, 2, and 3 in the excited states have been determined. Our results provide accurate experimental information for spectroscopic studies of the interesting vibrational perturbations and intermode interactions related to the C−N stretching mode, directly support astronomical surveys, and are very relevant in practice to identification and frequency determination of the CO2-laser-pumped far-infrared laser lines of methylamine.
Statistical and Ontological Analysis of Adverse Events Associated with Monovalent and Combination Vaccines against Hepatitis A and B Diseases
Authors: Xie Jiangan , Zhao Lili , Zhou Shangbo , He Yongqun 
Published: October 2016

AbstractVaccinations often induce various adverse events (AEs) and sometimes serious AEs (SAEs). While many vaccines are used in combination, the effects of vaccine-vaccine interactions (VVIs) on vaccine AEs are rarely studied. In this study, AE profiles induced by hepatitis A vaccine (Havrix), hepatitis B vaccine (Engerix-B) and hepatitis A and B combination vaccine (Twinrix) were studied using the VAERS data. From May 2001 to January 2015, VAERS recorded 941, 3,885 and 1,624 AE case reports where patients aged at least 18 years old were vaccinated with only Havrix, Engerix-B and Twinrix, respectively. Using these data, our statistical analysis identified 46, 69 and 82 AEs significantly associated with Havrix, Engerix-B and Twinrix, respectively. Based on the Ontology of Adverse Events (OAE) hierarchical classification, these AEs were enriched in the AEs related to behavioral and neurological conditions, immune system and investigation results. Twenty-nine AEs were classified as SAEs and mainly related to immune conditions. Using a logistic regression model accompanied with MCMC sampling, 13 AEs (e.g., hepatosplenomegaly) were identified to result from VVI synergistic effects. Classifications of these 13 AEs using OAE and MedDRA hierarchies confirmed the advantages of the OAE-based method over MedDRA in AE term hierarchical analysis.
Disruption of phenylalanine hydroxylase reduces adult lifespan and fecundity, and impairs embryonic development in parthenogenetic pea aphids
Authors: Simonet Pierre , Gaget Karen , Parisot Nicolas , Duport Gabrielle , Rey Marjolaine , Febvay Gérard , Charles Hubert , Callaerts Patrick , Colella Stefano , Calevro Federica 
Published: October 2016

AbstractPhenylalanine hydroxylase (PAH) is a key tyrosine-biosynthetic enzyme involved in neurological and melanin-associated physiological processes. Despite extensive investigations in holometabolous insects, a PAH contribution to insect embryonic development has never been demonstrated. Here, we have characterized, for the first time, the PAH gene in a hemimetabolous insect, the aphid Acyrthosiphon pisum. Phylogenetic and sequence analyses confirmed that ApPAH is closely related to metazoan PAH, exhibiting the typical ACT regulatory and catalytic domains. Temporal expression patterns suggest that ApPAH has an important role in aphid developmental physiology, its mRNA levels peaking at the end of embryonic development. We used parental dsApPAH treatment to generate successful knockdown in aphid embryos and to study its developmental role. ApPAH inactivation shortens the adult aphid lifespan and considerably affects fecundity by diminishing the number of nymphs laid and impairing embryonic development, with newborn nymphs exhibiting severe morphological defects. Using single nymph HPLC analyses, we demonstrated a significant tyrosine deficiency and a consistent accumulation of the upstream tyrosine precursor, phenylalanine, in defective nymphs, thus confirming the RNAi-mediated disruption of PAH activity. This study provides first insights into the role of PAH in hemimetabolous insects and demonstrates that this metabolic gene is essential for insect embryonic development.
An Adaptive Fisher’s Combination Method for Joint Analysis of Multiple Phenotypes in Association Studies
Authors: Liang Xiaoyu , Wang Zhenchuan , Sha Qiuying , Zhang Shuanglin 
Published: October 2016

AbstractCurrently, the analyses of most genome-wide association studies (GWAS) have been performed on a single phenotype. There is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Therefore, using only one single phenotype may lose statistical power to identify the underlying genetic mechanism. There is an increasing need to develop and apply powerful statistical tests to detect association between multiple phenotypes and a genetic variant. In this paper, we develop an Adaptive Fisher’s Combination (AFC) method for joint analysis of multiple phenotypes in association studies. The AFC method combines p-values obtained in standard univariate GWAS by using the optimal number of p-values which is determined by the data. We perform extensive simulations to evaluate the performance of the AFC method and compare the power of our method with the powers of TATES, Tippett’s method, Fisher’s combination test, MANOVA, MultiPhen and SUMSCORE. Our simulation studies show that the proposed method has correct type I error rates and is either the most powerful test or comparable with the most powerful test. Finally, we illustrate our proposed methodology by analyzing whole-genome genotyping data from a lung function study.
Electrochemical aptasensor for lung cancer-related protein detection in crude blood plasma samples
Authors: Zamay Galina S. , Zamay Tatiana N. , Kolovskii Vasilii A. , Shabanov Alexandr V. , Glazyrin Yury E. , Veprintsev Dmitry V. , Krat Alexey V. , Zamay Sergey S. , Kolovskaya Olga S. , Gargaun Ana , Sokolov Alexey E. , Modestov Andrey A. , Artyukhov Ivan P. , Chesnokov Nikolay V. , Petrova Marina M. , Berezovski Maxim V. , Zamay Anna S. 
Published: October 2016

AbstractThe development of an aptamer-based electrochemical sensor for lung cancer detection is presented in this work. A highly specific DNA-aptamer, LC-18, selected to postoperative lung cancer tissues was immobilized onto a gold microelectrode and electrochemical measurements were performed in a solution containing the redox marker ferrocyanide/ferricyanide. The aptamer protein targets were harvested from blood plasma of lung cancer patients by using streptavidin paramagnetic beads and square wave voltammetry of the samples was performed at various concentrations. In order to enhance the sensitivity of the aptasensor, silica-coated iron oxide magnetic beads grafted with hydrophobic C8 and C4 alkyl groups were used in a sandwich detection approach. Addition of hydrophobic beads increased the detection limit by 100 times. The detection limit of the LC-18 aptasensor was enhanced by the beads to 0.023 ng/mL. The formation of the aptamer – protein – bead sandwich on the electrode surface was visualized by electron microcopy. As a result, the electrochemical aptasensor was able to detect cancer-related targets in crude blood plasma of lung cancer patients.
High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells
Authors: Wang Hui , Zhang Songjin , Tian Xiumei , Liu Chufeng , Zhang Lei , Hu Wenyong , Shao Yuanzhi , Li Li 
Published: October 2016

AbstractNanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers.
Subcellular and in-vivo Nano-Endoscopy
Authors: Cheemalapati Surya Venkatasekhar , Winskas John , Wang Hao , Konnaiyan Karthik , Zhdanov Arseny , Roth Alison , Adapa Swamy Rakesh , Deonarine Andrew , Noble Mark , Das Tuhin , Gatenby Robert , Westerheide Sandy D. , Jiang Rays H. Y. , Pyayt Anna 
Published: October 2016

AbstractAnalysis of individual cells at the subcellular level is important for understanding diseases and accelerating drug discovery. Nanoscale endoscopes allow minimally invasive probing of individual cell interiors. Several such instruments have been presented previously, but they are either too complex to fabricate or require sophisticated external detectors because of low signal collection efficiency. Here we present a nanoendoscope that can locally excite fluorescence in labelled cell organelles and collect the emitted signal for spectral analysis. Finite Difference Time Domain (FDTD) simulations have shown that with an optimized nanoendoscope taper profile, the light emission and collection was localized within ~100 nm. This allows signal detection to be used for nano-photonic sensing of the proximity of fluorophores. Upon insertion into the individual organelles of living cells, the nanoendoscope was fabricated and resultant fluorescent signals collected. This included the signal collection from the nucleus of Acridine orange labelled human fibroblast cells, the nucleus of Hoechst stained live liver cells and the mitochondria of MitoTracker Red labelled MDA-MB-231 cells. The endoscope was also inserted into a live organism, the yellow fluorescent protein producing nematode Caenorhabditis elegans and a fluorescent signal was collected. To our knowledge this is the first demonstration of in vivo, local fluorescence signal collection on the sub-organelle level.