bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights into the mechanism of the PIK3CA E545K activating mutation using MD simulations
Authors: Leontiadou Hari , Galdadas Ioannis , Athanasiou Christina , Cournia Zoe 
Published: October 2018

AbstractPhosphoinositide 3-kinase alpha (PI3Kα) is involved in fundamental cellular processes including cell proliferation and differentiation and is frequently mutated in human malignancies. One of the most common mutations is E545K, which results in an amino acid substitution of opposite charge. It has been recently proposed that in this oncogenic charge-reversal mutation, the interactions between the protein catalytic and regulatory subunits are abrogated, resulting in loss of regulation and constitutive PI3Kα activity, which can lead to oncogenesis. To assess the mechanism of the PI3Kα E545K activating mutation, extensive Molecular Dynamics simulations were performed to examine conformational changes differing between the wild type (WT) and mutant proteins as they occur in microsecond simulations. In the E545K mutant PI3Kα, we observe a spontaneous detachment of the nSH2 PI3Kα domain (regulatory subunit, p85α) from the helical domain (catalytic subunit, p110α) causing significant loss of communication between the regulatory and catalytic subunits. We examine the allosteric network of the two proteins and show that a cluster of residues around the mutation is important for delivering communication signals between the catalytic and regulatory subunits. Our results demonstrate the dynamical and structural effects induced by the p110α E545K mutation in atomic level detail and indicate a possible mechanism for the loss of regulation that E545K confers on PI3Kα.
Bidirectional and context-dependent changes in theta and gamma oscillatory brain activity in noradrenergic cell-specific Hypocretin/Orexin receptor 1-KO mice
Authors: Li Sha , Franken Paul , Vassalli Anne 
Published: October 2018

AbstractNoradrenaline (NA) and hypocretins/orexins (HCRT), and their receptors, dynamically modulate the circuits that configure behavioral states, and their associated oscillatory activities. Salient stimuli activate spiking of locus coeruleus noradrenergic (NALC) cells, inducing NA release and brain-wide noradrenergic signalling, thus resetting network activity, and mediating an orienting response. Hypothalamic HCRT neurons provide one of the densest input to NALC cells. To functionally address the HCRT-to-NA connection, we selectively disrupted the Hcrtr1 gene in NA neurons, and analyzed resulting (Hcrtr1Dbh-CKO) mice’, and their control littermates’ electrocortical response in several contexts of enhanced arousal. Under enforced wakefulness (EW), or after cage change (CC), Hcrtr1Dbh-CKO mice exhibited a weakened ability to lower infra-θ frequencies (1–7 Hz), and mount a robust, narrow-bandwidth, high-frequency θ rhythm (~8.5 Hz). A fast-γ (55–80 Hz) response, whose dynamics closely parallelled θ, also diminished, while β/slow-γ activity (15–45 Hz) increased. Furthermore, EW-associated locomotion was lower. Surprisingly, nestbuilding-associated wakefulness, inversely, featured enhanced θ and fast-γ activities. Thus HCRT-to-NA signalling may fine-tune arousal, up in alarming conditions, and down during self-motivated, goal-driven behaviors. Lastly, slow-wave-sleep following EW and CC, but not nestbuilding, was severely deficient in slow-δ waves (0.75–2.25 Hz), suggesting that HCRT-to-NA signalling regulates the slow-δ rebound characterizing sleep after stress-associated arousal.
Studies on effects of static electric field exposure on liver in mice
Authors: Lin Qinhao , Dong Li , Xu Yaqian , Di Guoqing 
Published: October 2018

AbstractWith the development of ultra-high-voltage direct-current transmission, the intensity of static electric field (SEF) under transmission lines increased, which has aroused public attention on its potential health effects. In order to examine effects of SEF exposure on liver, institute of cancer research mice were exposed to SEF with intensities of 27.5 kV/m, 34.7 kV/m and 56.3 kV/m, respectively. In each intensity of SEF exposure, a corresponding sham exposure group was used. Several indices relating to liver function (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA)) were tested after exposure of 7, 14, 21 and 35 days. Results showed that exposure to SEF with intensities of 27.5 kV/m and 34.7 kV/m for 35 days did not significantly influence any detected indices above. Under SEF exposure with intensity of 56.3 kV/m, the SOD activity in liver was significantly increased after exposure of 7 and 14 days. However, no significant increase was found in MDA content as well as the activities of AST and ALT between exposure group and sham exposure group during SEF exposure of 56.3 kV/m. It suggested that from three SEF intensities, only exposure to SEF with intensity of 56.3 kV/m (7 and 14 days) caused a temporary oxidative stress response in liver expressed by the increase in activity of SOD, but it did not produce oxidative damage. This biological effect may be related to the increase of mitochondrial membrane potential of hepatocytes caused by SEF exposure. When the membrane potential exceeds a threshold, Q cycle in mitochondria will be affected, which will result in an increase of superoxide anion concentration and ultimately an oxidative stress.
Deciphering the rationale behind specific codon usage pattern in extremophiles
Authors: Khan Mohd Faheem , Patra Sanjukta 
Published: October 2018

AbstractProtein stability is affected at different hierarchies – gene, RNA, amino acid sequence and structure. Gene is the first level which contributes via varying codon compositions. Codon selectivity of an organism differs with normal and extremophilic milieu. The present work attempts at detailing the codon usage pattern of six extremophilic classes and their harmony. Homologous gene datasets of thermophile-mesophile, psychrophile-mesophile, thermophile-psychrophile, acidophile-alkaliphile, halophile-nonhalophile and barophile-nonbarophile were analysed for filtering statistically significant attributes. Relative abundance analysis, 1–9 scale ranking, nucleotide compositions, attribute weighting and machine learning algorithms were employed to arrive at findings. AGG in thermophiles and barophiles, CAA in mesophiles and psychrophiles, TGG in acidophiles, GAG in alkaliphiles and GAC in halophiles had highest preference. Preference of GC-rich and G/C-ending codons were observed in halophiles and barophiles whereas, a decreasing trend was reflected in psychrophiles and alkaliphiles. GC-rich codons were found to decrease and G/C-ending codons increased in thermophiles whereas, acidophiles showed equal contents of GC-rich and G/C-ending codons. Codon usage patterns exhibited harmony among different extremophiles and has been detailed. However, the codon attribute preferences and their selectivity of extremophiles varied in comparison to non-extremophiles. The finding can be instrumental in codon optimization application for heterologous expression of extremophilic proteins.
Feedback Timing Modulates Probabilistic Learning in Adults with ADHD
Authors: Gabay Yafit , Shahbari-Khateb Elham , Mendelsohn Avi 
Published: October 2018

AbstractAttention deficit hyperactivity disorder (ADHD) has been associated primarily with executive function deficits. Emerging findings suggest, however, that procedural learning may be compromised as well. To this effect, we recently showed that feedback-based procedural learning is selectively impaired in ADHD, results that coincide with dopaminergic alterations associated with ADHD. Key questions, however, remain unresolved, among which are the learning conditions that may improve procedural learning in ADHD. Here we examined feedback-based probabilistic learning during conditions that engage procedural and declarative learning systems to different degrees, depending on feedback timing. ADHD and control participants carried out a probabilistic learning task in which they were required to learn to associate between cues and outcomes, where outcomes were presented either immediately or with a short/long delays. Whereas performance in probabilistic learning in ADHD participants was comparable to controls in delayed feedback conditions, during both learning and test phases, their performance diminished when feedback was immediate. Furthermore, ADHD symptom severity was negatively correlated with the ability to learn from immediate feedback. These results suggest that feedback-based probabilistic learning can be improved in ADHD, provided appropriate conditions. By shifting the load from midbrain/striatal systems to declarative memory mechanisms, behavioral performance in ADHD populations can be remediated.
Direct observation of symmetrization of hydrogen bond in δ-AlOOH under mantle conditions using neutron diffraction
Authors: Sano-Furukawa Asami , Hattori Takanori , Komatsu Kazuki , Kagi Hiroyuki , Nagai Takaya , Molaison Jamie J. , dos Santos António M. , Tulk Christopher A. 
Published: October 2018

AbstractAt ambient pressure, the hydrogen bond in materials such as ice, hydrates, and hydrous minerals that compose the Earth and icy planets generally takes an asymmetric O-H···O configuration. Pressure significantly affects this configuration, and it is predicted to become symmetric, such that the hydrogen is centered between the two oxygen atoms at high pressure. Changes of physical properties of minerals relevant to this symmetrization have been found; however, the atomic configuration around this symmetrization has remained elusive so far. Here we observed the pressure response of the hydrogen bonds in the aluminous hydrous minerals δ-AlOOH and δ-AlOOD by means of a neutron diffraction experiment. We find that the transition from P21nm to Pnnm at 9.0 GPa, accompanied by a change in the axial ratios of δ-AlOOH, corresponds to the disorder of hydrogen bond between two equivalent sites across the center of the O···O line. Symmetrization of the hydrogen bond is observed at 18.1 GPa, which is considerably higher than the disorder pressure. Moreover, there is a significant isotope effect on hydrogen bond geometry and transition pressure. This study indicates that disorder of the hydrogen bond as a precursor of symmetrization may also play an important role in determining the physical properties of minerals such as bulk modulus and seismic wave velocities in the Earth’s mantle.
Deep sequencing of primary human lung epithelial cells challenged with H5N1 influenza virus reveals a proviral role for CEACAM1
Authors: Ye Siying , Cowled Christopher J. , Yap Cheng-Hon , Stambas John 
Published: October 2018

AbstractCurrent prophylactic and therapeutic strategies targeting human influenza viruses include vaccines and antivirals. Given variable rates of vaccine efficacy and antiviral resistance, alternative strategies are urgently required to improve disease outcomes. Here we describe the use of HiSeq deep sequencing to analyze host gene expression in primary human alveolar epithelial type II cells infected with highly pathogenic avian influenza H5N1 virus. At 24 hours post-infection, 623 host genes were significantly upregulated, including the cell adhesion molecule CEACAM1. H5N1 virus infection stimulated significantly higher CEACAM1 protein expression when compared to influenza A PR8 (H1N1) virus, suggesting a key role for CEACAM1 in influenza virus pathogenicity. Furthermore, silencing of endogenous CEACAM1 resulted in reduced levels of proinflammatory cytokine/chemokine production, as well as reduced levels of virus replication following H5N1 infection. Our study provides evidence for the involvement of CEACAM1 in a clinically relevant model of H5N1 infection and may assist in the development of host-oriented antiviral strategies.
Enhanced sensitivity in THz plasmonic sensors with silver nanowires
Authors: Hong J. T. , Jun S. W. , Cha S. H. , Park J. Y. , Lee S. , Shin G. A. , Ahn Y. H. 
Published: October 2018

AbstractWe developed hybrid slot antenna structures for microbial sensing in the THz frequency range, where silver nanowires (AgNWs) were employed to increase the sensitivity. In order to fabricate the hybrid devices, we partially etched the AgNW in the slot antenna region, where we can expect the field enhancement effect at the AgNW tip. We measured the resonant-frequency shift observed upon the deposition of a polymer layer, and observed that the sensitivity increased upon the introduction of AgNWs, with an enhancement factor of more than four times (approximately six times in terms of figure-of-merit). The sensitivity increased with the AgNW density until saturation. In addition, we tested devices with PRD1 viruses, and obtained an enhancement factor of 3.4 for a slot antenna width of 3 μm. Furthermore, we performed finite-difference time-domain simulations, which confirmed the experimental results. The sensitivity enhancement factor decreased with the decrease of the slot width, consistent with the experimental findings. Two-dimensional mapping of the electric field confirmed the strong field localization and enhancement at the AgNW tips.
Short-term enhancement of cognitive functions and music: A three-channel model
Authors: Gupta Ashish , Bhushan Braj , Behera Laxmidhar 
Published: October 2018

AbstractShort-term effects of music stimulus on enhancement of cognitive functions in human brain are documented, however the underlying neural mechanisms in these cognitive effects are not well investigated. In this study, we have attempted to decipher the mechanisms involved in alterations of neural networks that lead to enhanced cognitive effects post-exposure to music. We have investigated the changes in Electroencephalography (EEG) power and functional connectivity of alpha band in resting state of the brain after exposure to Indian classical music. We have quantified the changes in functional connectivity by phase coherence, phase delay, and phase slope index analyses. Spatial mapping of functional connectivity dynamics thus obtained, on brain networks revealed reduced information flow in long-distance connections between frontal and parietal cortex, and between other cortical regions underpinning intelligence. Analyses also showed increased power in the prefrontal and occipital cortex. With these findings, we have developed a stimulus-mechanism-end effect based neuro-cognitive model that explains the music induced cognitive enhancement by a three-channel framework - (1) enhanced global efficiency of brain, (2) enhanced local neural efficiency at the prefrontal lobe, and (3) increased sustained attention. Results signify that music directly affects the cognitive system and leads to improved brain efficiency through well-defined mechanisms.
Implicit time-place conditioning alters Per2 mRNA expression selectively in striatum without shifting its circadian clocks
Authors: Shrestha Tenjin C. , Šuchmanová Karolína , Houdek Pavel , Sumová Alena , Ralph Martin R. 
Published: October 2018

AbstractAnimals create implicit memories of the time of day that significant events occur then anticipate the recurrence of those conditions at the same time on subsequent days. We tested the hypothesis that implicit time memory for daily encounters relies on the setting of the canonical circadian clockwork in brain areas involved in the formation or expression of context memories. We conditioned mice to avoid locations paired with a mild foot shock at one of two Zeitgeber times set 8 hours apart. Place avoidance was exhibited only when testing time matched the prior training time. The suprachiasmatic nucleus, dorsal striatum, nucleus accumbens, cingulate cortex, hippocampal complex, and amygdala were assessed for clock gene expression. Baseline phase dependent differences in clock gene expression were found in most tissues. Evidence for conditioned resetting of a molecular circadian oscillation was found only in the striatum (dorsal striatum and nucleus accumbens shell), and specifically for Per2 expression. There was no evidence of glucocorticoid stress response in any tissue. The results are consistent with a model where temporal conditioning promotes a selective Per2 response in dopamine-targeted brain regions responsible for sensorimotor integration, without resetting the entire circadian clockwork.
Disentangling direct and indirect effects of water availability, vegetation, and topography on avian diversity
Authors: Remeš Vladimír , Harmáčková Lenka 
Published: October 2018

AbstractClimate is a major driver of species diversity. However, its effect can be either direct due to species physiological tolerances or indirect, whereby wetter climates facilitate more complex vegetation and consequently higher diversity due to greater resource availability. Yet, studies quantifying both direct and indirect effects of climate on multiple dimensions of diversity are rare. We used extensive data on species distributions, morphological and ecological traits, and vegetation across Australia to quantify both direct (water availability) and indirect (habitat diversity and canopy height) effects of climate on the species richness (SR), phylogenetic diversity (PD), and functional diversity (FD) of 536 species of birds. Path analyses revealed that SR increased with wetter climates through both direct and indirect effects, lending support for the influence of both physiological tolerance and vegetation complexity. However, residual PD and residual FD (adjusted for SR by null models) were poorly predicted by environmental conditions. Thus, the FD and PD of Australian birds mostly evolved in concert with SR, with the possible exception of the higher-than-expected accumulation of avian lineages in wetter and more productive areas in northern and eastern Australia (with high residual PD), permitted probably by older biome age.
Measuring Abnormality in High Dimensional Spaces with Applications in Biomechanical Gait Analysis
Authors: Marks Michael , Kingsbury Trevor , Bryant Richard , Collins John David , Wyatt Marilynn 
Published: October 2018

AbstractAccurately measuring a subject’s abnormality using high dimensional data can empower better outcomes research. Utilizing applications in instrumented gait analysis, this article demonstrates how using data that is inherently non-independent to measure overall abnormality may bias results. A methodology is then introduced to address this bias and accurately measure abnormality in high dimensional spaces. While this methodology is in line with previous literature, it differs in two major ways. Advantageously, it can be applied to datasets in which the number of observations is less than the number of features/variables, and it can be abstracted to practically any number of domains or dimensions. Initial results of these methods show that they can detect known, real-world differences in abnormality between subject groups where established measures could not. This methodology is made freely available via theabnormalityR package on CRAN.
A closer look at neuron interaction with track-etched microporous membranes
Authors: George Julian H. , Nagel David , Waller Sharlayne , Hill Eric , Parri H. Rhein , Coleman Michael D. , Cui Zhanfeng , Ye Hua 
Published: October 2018

AbstractMicroporous membranes support the growth of neurites into and through micro-channels, providing a different type of neural growth platform to conventional dish cultures. Microporous membranes are used to support various types of culture, however, the role of pore diameter in relation to neurite growth through the membrane has not been well characterised. In this study, the human cell line (SH-SY5Y) was differentiated into neuron-like cells and cultured on track-etched microporous membranes with pore and channel diameters selected to accommodate neurite width (0.8 µm to 5 µm). Whilst neurites extended through all pore diameters, the extent of neurite coverage on the non-seeded side of the membranes after 5 days in culture was found to be directly proportional to channel diameter. Neurite growth through membrane pores reduced significantly when neural cultures were non-confluent. Scanning electron microscopy revealed that neurites bridged pores and circumnavigated pore edges – such that the overall likelihood of a neurite entering a pore channel was decreased. These findings highlight the role of pore diameter, cell sheet confluence and contact guidance in directing neurite growth through pores and may be useful in applications that seek to use physical substrates to maintain separate neural populations whilst permitting neurite contact between cultures.
Ultra-Bright Near-Infrared Perovskite Light-Emitting Diodes with Reduced Efficiency Roll-off
Authors: Giuri Antonella , Yuan Zhongcheng , Miao Yanfeng , Wang Jianpu , Gao Feng , Sestu Nicola , Saba Michele , Bongiovanni Giovanni , Colella Silvia , Esposito Corcione Carola , Gigli Giuseppe , Listorti Andrea , Rizzo Aurora 
Published: October 2018

AbstractHerein, an insulating biopolymer is exploited to guide the controlled formation of micro/nano-structure and physical confinement of α-δ mixed phase crystalline grains of formamidinium lead iodide (FAPbI3) perovskite, functioning as charge carrier concentrators and ensuring improved radiative recombination and photoluminescence quantum yield (PLQY). This composite material is used to build highly efficient near-infrared (NIR) FAPbI3 Perovskite light-emitting diodes (PeLEDs) that exhibit a high radiance of 206.7 W/sr*m2, among the highest reported for NIR-PeLEDs, obtained at a very high current density of 1000 mA/cm2, while importantly avoiding the efficiency roll-off effect. In depth photophysical characterization allows to identify the possible role of the biopolymer in i) enhancing the radiative recombination coefficient, improving light extraction by reducing the refractive index, or ii) enhancing the effective optical absorption because of dielectric scattering at the polymer-perovskite interfaces. Our study reveals how the use of insulating matrixes for the growth of perovskites represents a step towards high power applications of PeLEDs.
Association of cervical microbial community with persistence, clearance and negativity of Human Papillomavirus in Korean women: a longitudinal study
Authors: Arokiyaraj Selvaraj , Seo Sang Soo , Kwon Minji , Lee Jae Kwan , Kim Mi Kyung 
Published: October 2018

AbstractThe present study aimed to identify the cervical microbes that are associated with HPV negativity, HPV clearance and HPV persistence and to assess the microbes’ longitudinal associations as related to HPV infection dynamics among Korean women. We enrolled 41 women with 107 samples, and classified them according to the HPV infection dynamics: HPV negativity (21 samples, 10 subjects), HPV clearance (42 samples, 15 subjects), and HPV persistence (44 samples, 16 subjects). Cervical swabs were collected at the baseline and six-month-interval follow-up visits. HPV positivity was determined by HPV DNA HC2 assay, and the microbiome was analyzed using 16SrRNA pyrosequencing, linear discriminant analysis effect size and multivariate logistic analysis. In the multivariate logistic analysis results, Lactobacillus crispatus (multivariate OR (mOR) = 8.25, 95% CI 2.13~32.0) was predominant in the HPV-negative group. We observed that Eubacterium eligens (mOR = 11.5, 95% CI 1.31~101.4), Gardnerella vaginalis (mOR = 17.0, 95% CI 2.18–131.8), and Ureaplasma urealyticum (mOR = 7.42, 95% CI 1.3–42.46) had the strongest associations with HPV clearance, and Lactobacillus johnsonii (mOR = 16.4, 95% CI 1.77–152.2) with HPV persistence. Overall, greater diversity was observed in HPV-persistence than in HPV-negative women. Our findings suggest that the presence and prevalence of a specific cervical microbiome are factors involved in HPV dynamics.