bluuebunny/crossref_metadata_2025 huggingface dataset:
piRNA-like small RNAs are responsible for the maternal-specific knockdown in the ascidian Ciona intestinalis Type A
Authors: Satoh Teruki , Iitsuka Takako , Shiraishi Akira , Hozumi Akiko , Satake Honoo , Sasakura Yasunori
Published: April 2018

The mRNAs stored in eggs are crucial for embryogenesis. To address functions of maternal mRNAs, we recently reported the novel method MASK (maternal mRNA-specific knockdown), which we used to specifically knockdown maternal transcripts in the ascidian Ciona intestinalis Type A. In MASK, the cis element of a maternal gene is fused with eGFP or Kaede reporter gene, and the cassette is introduced into Ciona genome by transposon-mediated transgenesis. In eggs of the transgenic lines, the maternal expression of the gene whose cis element is used for driving the reporter gene is suppressed. The zygotic expression of the gene is not suppressed, suggesting that the MASK method can distinguish between maternal and zygotic functions of a gene. Here we investigated the cis and trans factors responsible for MASK results. In the ovaries in which knockdown of a maternal gene occurs, a number of antisense small RNAs are expressed that are complementary to the sequence of the knocked-down genes. We suspect that these antisense small RNAs are the factor responsible for MASK results. The antisense small RNAs have several features that are seen in PIWI-interacting RNAs (piRNAs), suggesting that MASK is likely to use a piRNA-mediated mechanism to knock down maternal mRNAs.
A fast and cost-effective method for apolipoprotein E isotyping as an alternative to APOE genotyping for patient screening and stratification
Authors: Calero Olga , García-Albert Luis , Rodríguez-Martín Andrés , Veiga Sergio , Calero Miguel
Published: April 2018

Apolipoprotein E (apoE) is a 34 kDa glycoprotein involved in lipid metabolism. The human APOE gene encodes for three different apoE protein isoforms: E2, E3 and E4. The interest in apoE isoforms is high for epidemiological research, patient stratification and identification of those at increased risk for clinical trials and prevention. The isoform apoE4 is associated with increased risk for coronary heart and Alzheimer’s diseases. This paper describes a method for specifically detecting the apoE4 isoform from biological fluids by taking advantage of the capacity of apoE to bind “specifically” to polystyrene surfaces as capture and a specific anti-apoE4 monoclonal antibody as reporter. Our results indicate that the apoE-polystyrene binding interaction is highly stable, resistant to detergents and acid and basic washes. The methodology here described is accurate, easily implementable, fast and cost-effective. Although at present, our technique is unable to discriminate homozygous APOE ε4/ε4 from APOE ε3/ε4 and ε2/ε4 heterozygous, it opens new avenues for the development of inexpensive, yet effective, tests for the detection of apoE4 for patients’ stratification. Preliminary results indicated that this methodology is also adaptable into turbidimetric platforms, which make it a good candidate for clinical implementation through its translation to the clinical analysis routine.
MEMS based highly sensitive dual FET gas sensor using graphene decorated Pd-Ag alloy nanoparticles for H2 detection
Authors: Sharma Bharat , Kim Jung-Sik
Published: April 2018

A low power, dual-gate field-effect transistor (FET) hydrogen gas sensor with graphene decorated Pd-Ag for hydrogen sensing applications was developed. The FET hydrogen sensor was integrated with a graphene-Pd-Ag-gate FET (GPA-FET) as hydrogen sensor coupled with Pt-gate FET as a reference sensor on a single sensor platform. The sensing gate electrode was modified with graphene by an e-spray technique followed by Pd-Ag DC/MF sputtering. Morphological and structural properties were studied by FESEM and Raman spectroscopy. FEM simulations were performed to confirm the uniform temperature control at the sensing gate electrode. The GPA-FET showed a high sensing response to hydrogen gas at the temperature of 25~254.5 °C. The as-proposed FET H2 sensor showed the fast response time and recovery time of 16 s, 14 s, respectively at the operating temperature of 245 °C. The variation in drain current was positively related with increased working temperature and hydrogen concentration. The proposed dual-gate FET gas sensor in this study has potential applications in various fields, such as electronic noses and automobiles, owing to its low-power consumption, easy integration, good thermal stability and enhanced hydrogen sensing properties.
Super-resolution for asymmetric resolution of FIB-SEM 3D imaging using AI with deep learning
Authors: Hagita Katsumi , Higuchi Takeshi , Jinnai Hiroshi
Published: April 2018

Scanning electron microscopy equipped with a focused ion beam (FIB-SEM) is a promising three-dimensional (3D) imaging technique for nano- and meso-scale morphologies. In FIB-SEM, the specimen surface is stripped by an ion beam and imaged by an SEM installed orthogonally to the FIB. The lateral resolution is governed by the SEM, while the depth resolution, i.e., the FIB milling direction, is determined by the thickness of the stripped thin layer. In most cases, the lateral resolution is superior to the depth resolution; hence, asymmetric resolution is generated in the 3D image. Here, we propose a new approach based on an image-processing or deep-learning-based method for super-resolution of 3D images with such asymmetric resolution, so as to restore the depth resolution to achieve symmetric resolution. The deep-learning-based method learns from high-resolution sub-images obtained via SEM and recovers low-resolution sub-images parallel to the FIB milling direction. The 3D morphologies of polymeric nano-composites are used as test images, which are subjected to the deep-learning-based method as well as conventional methods. We find that the former yields superior restoration, particularly as the asymmetric resolution is increased. Our super-resolution approach for images having asymmetric resolution enables observation time reduction.
Electrically Enhanced Self-Thermophoresis of Laser-Heated Janus Particles under a Rotating Electric Field
Authors: Chen Yu-Liang , Yang Cheng-Xiang , Jiang Hong-Ren
Published: April 2018

The motion of a laser-heated Janus particle is experimentally measured under a rotating electric field. Directionally circular motions of the Janus particle following or countering the direction of the rotating electric field are observed in the low-frequency region (from 1 to 6 kHz) depending on the direction of electrorotation. In the higher frequency region (>10 kHz), only pure electrorotation and electrothermal flow are observed. By measuring the dependence of the frequency, voltage, and laser heating power, we propose that the tangential component of circular motion is caused by electric field enhanced self-thermophoresis, which is proportional to the laser heating power and the electric field. This result indicates that thermophoresis could be modified by the induced zeta potential of the Janus particle tuned by the applied electric fields. By this mechanism, the intrinsic thermophoresis can be enhanced several times at a relatively low applied voltage (~3 Volt). Electrically tunable thermophoresis of a particle may bring new insights to thermophoresis phenomenon and also open a new direction for tunable active materials.
Effect of antibiotic use for acute bronchiolitis on new-onset asthma in children
Authors: Chen I.-Lun , Huang Hsin-Chun , Chang Yu-Han , Huang Hsin-Yi , Yeh Wei-Ju , Wu Ting-Yi , Suen Jau-Ling , Yang San-Nan , Hung Chih-Hsing
Published: April 2018

Early-life use of antibiotics is associated with asthma. We examined the effect of antibiotic use for early-life bronchiolitis on the development of new-onset asthma in children from Taiwan between 2005 and 2010. Data were from the National Health Insurance Research Database 2010, and diseases were coded using the International Classification of Disease (ICD). We classified the patients, all of whom had bronchiolitis, as having asthma or not having asthma. Asthma was diagnosed using ICD criteria and by use of an inhaled bronchodilator and/or corticosteroid twice in one year. We identified age at asthma onset, sex, residential area, history of atopy and NSAID use, age at first use of antibiotics, and the specific antibiotic, and adjusted for these factors using conditional logistic regression analysis. Among all individuals, there was a relationship between risk of new-onset asthma with use of a high dose of an antibiotic (adjusted odds ratio [aOR] = 3.33, 95% confidence interval [CI] = 2.67–4.15). Among the different antibiotics, macrolides (aOR = 2.87, 95% CI = 1.99–4.16), and azithromycin specifically (aOR = 3.45, 95% CI = 1.62–7.36), had the greatest effect of development of asthma.
Mechanical Tension Drives Elongational Growth of the Embryonic Gut
Authors: Chevalier Nicolas R. , de Witte Tinke-Marie , Cornelissen Annemiek J. M. , Dufour Sylvie , Proux-Gillardeaux Véronique , Asnacios Atef
Published: April 2018

During embryonic development, most organs are in a state of mechanical compression because they grow in a confined and limited amount of space within the embryo’s body; the early gut is an exception because it physiologically herniates out of the coelom. We demonstrate here that physiological hernia is caused by a tensile force transmitted by the vitelline duct on the early gut loop at its attachment point at the umbilicus. We quantify this tensile force and show that applying tension for 48 h induces stress-dependent elongational growth of the embryonic gut in culture, with an average 90% length increase (max: 200%), 65% volume increase (max: 160%), 50% dry mass increase (max: 100%), and 165% cell number increase (max: 300%); this mechanical cue is required for organ growth as guts not subject to tension do not grow. We demonstrate that growth results from increased cell proliferation when tension is applied. These results outline the essential role played by mechanical forces in shaping and driving the proliferation of embryonic organs.
Application of interspecific Somatic Cell Nuclear Transfer (iSCNT) in sturgeons and an unexpectedly produced gynogenetic sterlet with homozygous quadruple haploid
Authors: Fatira Effrosyni , Havelka Miloš , Labbé Catherine , Depincé Alexandra , Iegorova Viktoriia , Pšenička Martin , Saito Taiju
Published: April 2018

Somatic cell nuclear transfer (SCNT) is a very promising cloning technique for reconstruction of endangered animals. The aim of the present research is to implement the interspecific SCNT (iSCNT) technique to sturgeon; one fish family bearing some of the most critically endangered species. We transplanted single cells enzymatically isolated from a dissociated fin-fragment of the Russian sturgeon (Acipenser gueldenstaedtii) into non-enucleated eggs of the sterlet (Acipenser ruthenus), two species bearing different ploidy (4n and 2n, respectively). Up to 12% of the transplanted eggs underwent early development, and one feeding larva (0.5%) was successfully produced. Interestingly, although this transplant displayed tetraploidism (4n) as the donor species, the microsatellite and species-specific analysis showed recipient-exclusive homozygosis without any donor markers. Namely, with regards to this viable larva, host genome duplication occurred twice to form tetraploidism during its early development, probably due to iSCNT manipulation. The importance of this first attempt is to apply iSCNT in sturgeon species, establishing the crucial first steps by adjusting the cloning-methodology in sturgeon’s biology. Future improvements in sturgeon’s cloning are necessary for providing with great hope in sturgeon’s reproduction.
Intact interleukin-10 receptor signaling protects from hippocampal damage elicited by experimental neurotropic virus infection of SJL mice
Authors: Uhde Ann-Kathrin , Ciurkiewicz Malgorzata , Herder Vanessa , Khan Muhammad Akram , Hensel Niko , Claus Peter , Beckstette Michael , Teich René , Floess Stefan , Baumgärtner Wolfgang , Jung Klaus , Huehn Jochen , Beineke Andreas
Published: April 2018

Theiler’s murine encephalomyelitis virus (TMEV) infection represents an experimental mouse model to study hippocampal damage induced by neurotropic viruses. IL-10 is a pleiotropic cytokine with profound anti-inflammatory properties, which critically controls immune homeostasis. In order to analyze IL-10R signaling following virus-induced polioencephalitis, SJL mice were intracerebrally infected with TMEV. RNA-based next generation sequencing revealed an up-regulation ofIl10,Il10rαand further genes involved in IL-10 downstream signaling, includingJak1,Socs3andStat3in the brain upon infection. Subsequent antibody-mediated blockade of IL-10R signaling led to enhanced hippocampal damage with neuronal loss and increased recruitment of CD3+T cells, CD45R+B cells and an up-regulation ofIl1αmRNA. Increased expression ofTgfβandFoxp3as well as accumulation of Foxp3+regulatory T cells and arginase-1+macrophages/microglia was detected in the hippocampus, representing a potential compensatory mechanism following disturbed IL-10R signaling. Additionally, an increased peripheralChi3l3expression was found in spleens of infected mice, which may embody reactive regulatory mechanisms for prevention of excessive immunopathology. The present study highlights the importance of IL-10R signaling for immune regulation and its neuroprotective properties in the context of an acute neurotropic virus infection.
Effects of noise on the internal resonance of a nonlinear oscillator
Authors: Zanette Damián H.
Published: April 2018

We numerically analyze the response to noise of a system formed by two coupled mechanical oscillators, one of them having Duffing and van der Pol nonlinearities, and being excited by a self–sustaining force proportional to its own velocity. This system models the internal resonance of two oscillation modes in a vibrating solid beam clamped at both ends. In applications to nano– and micromechanical devices, clamped–clamped beams are subjected to relatively large thermal and electronic noise, so that characterizing the fluctuations induced by these effects is an issue of both scientific and technological interest. We pay particular attention to the action of stochastic forces on the stability of internal–resonance motion, showing that resonant oscillations become more robust than other forms of periodic motion as the quality factor of the resonant mode increases. The dependence on other model parameters —in particular, on the coupling strength between the two oscillators— is also assessed.
Asymmetric wave transmission through one dimensional lattices with cubic-quintic nonlinearity
Authors: Wasay Muhammad Abdul
Published: April 2018

One dimensional lattice with an on-site cubic-quintic nonlinear response described by a cubic-quintic discrete nonlinear Schrödinger equation is tested for asymmetric wave propagation. The lattice is connected to linear side chains. Asymmetry is introduced by breaking the mirror symmetry of the lattice with respect to the center of the nonlinear region. Three cases corresponding to dimer, trimer and quadrimer are discussed with focus on the corresponding diode-like effect. Transmission coefficients are analytically calculated for left and right moving waves via backward transfer map. The different transmission coefficients for the left and right moving waves impinging the lattice give rise to a diode-like effect which is tested for different variations in asymmetry and site dependent coefficients. We show that there is a higher transmission for incoming waves with lower wavenumbers as compared to the waves with comparatively larger wavenumbers and a diode-like effect improves by increasing the nonlinear layers. We also show that in the context of transport through such lattices, the cooperation between cubic and quintic nonlinear response is not “additive”. Finally, we numerically analyse Gaussian wave packet dynamics impinging on the CQDNLS lattice for all three cases.
Safety of Low-calcium Dialysate and its Effects on Coronary Artery Calcification in Patients Undergoing Maintenance Hemodialysis
Authors: Wen Yang , Gan Hua , Li Zhengrong , Sun Ximin , Xiong Ying , Xia Yunfeng
Published: April 2018

To determine the safety of low-calcium-dialysate in patients undergoing maintenance hemodialysis (MHD) and its effects on coronary artery calcification (CAC) and analyze clinical risk factors for CAC. A total of 174 MHD patients were recruited and randomly divided into two groups: high-calcium dialysate (HCD, 1.5 mmol/L Ca2+) and low-calcium dialysate (LCD, 1.25 mmol/L Ca2+). Changes in CAC score (CACS) and cardiac function were evaluated using spiral computed tomography and echocardiography, respectively. Clinical and laboratory parameters were measured. Intra-dialysis adverse reactions were recorded and compared between the two groups. CACS was significantly lower in the LCD group than in the HCD group by the end of the study. Cardiac E/Amax was significantly higher in the LCD group than in the HCD group by the end of the study. There was no significant difference in the frequency of any intra-dialysis adverse reactions between the two groups during the study. LCD is helpful in maintaining cardiac diastolic function and postponing CAC progression. LCD does not increase intra-dialysis adverse reactions. Age may be the most important factor impacting CAC in MHD patients.
Time rescaling reproduces EEG behavior during transition from propofol anesthesia-induced unconsciousness to consciousness
Authors: Boussen S. , Spiegler A. , Benar C. , Carrère M. , Bartolomei F. , Metellus P. , Voituriez R. , Velly L. , Bruder N. , Trébuchon A.
Published: April 2018

General anesthesia (GA) is a reversible manipulation of consciousness whose mechanism is mysterious at the level of neural networks leaving space for several competing hypotheses. We recorded electrocorticography (ECoG) signals in patients who underwent intracranial monitoring during awake surgery for the treatment of cerebral tumors in functional areas of the brain. Therefore, we recorded the transition from unconsciousness to consciousness directly on the brain surface. Using frequency resolved interferometry; we studied the intermediate ECoG frequencies (4–40 Hz). In the theoretical study, we used a computational Jansen and Rit neuron model to simulate recovery of consciousness (ROC). During ROC, we found thatfincreased by a factor equal to 1.62 ± 0.09, andδfvaried by the same factor (1.61 ± 0.09) suggesting the existence of a scaling factor. We accelerated the time course of an unconscious EEG trace by an approximate factor 1.6 and we showed that the resulting EEG trace match the conscious state. Using the theoretical model, we successfully reproduced this behavior. We show that the recovery of consciousness corresponds to a transition in the frequency (f, δf) space, which is exactly reproduced by a simple time rescaling. These findings may perhaps be applied to other altered consciousness states.
Detection and characterisation of coronaviruses in migratory and non-migratory Australian wild birds
Authors: Chamings Anthony , Nelson Tiffanie M. , Vibin Jessy , Wille Michelle , Klaassen Marcel , Alexandersen Soren
Published: April 2018

We evaluated the presence of coronaviruses by PCR in 918 Australian wild bird samples collected during 2016–17. Coronaviruses were detected in 141 samples (15.3%) from species of ducks, shorebirds and herons and from multiple sampling locations. Sequencing of selected positive samples found mainly gammacoronaviruses, but also some deltacoronaviruses. The detection rate of coronaviruses was improved by using multiple PCR assays, as no single assay could detect all coronavirus positive samples. Sequencing of the relatively conserved Orf1 PCR amplicons found that Australian duck gammacoronaviruses were similar to duck gammacoronaviruses around the world. Some sequenced shorebird gammacoronaviruses belonged to Charadriiformes lineages, but others were more closely related to duck gammacoronaviruses. Australian duck and heron deltacoronaviruses belonged to lineages with other duck and heron deltacoronaviruses, but were almost 20% different in nucleotide sequence to other deltacoronavirus sequences available. Deltacoronavirus sequences from shorebirds formed a lineage with a deltacoronavirus from a ruddy turnstone detected in the United States. Given that Australian duck gammacoronaviruses are highly similar to those found in other regions, and Australian ducks rarely come into contact with migratory Palearctic duck species, we hypothesise that migratory shorebirds are the important vector for moving wild bird coronaviruses into and out of Australia.
Role of the Interplay Between the Internal and External Conditions in Invasive Behavior of Tumors
Authors: Azimzade Youness , Saberi Abbas Ali , Sahimi Muhammad
Published: April 2018

Tumor growth, which plays a central role in cancer evolution, depends on both the internal features of the cells, such as their ability for unlimited duplication, and the external conditions, e.g., supply of nutrients, as well as the dynamic interactions between the two. A stem cell theory of cancer has recently been developed that suggests the existence of a subpopulation of self-renewing tumor cells to be responsible for tumorigenesis, and is able to initiate metastatic spreading. The question of abundance of the cancer stem cells (CSCs) and its relation to tumor malignancy has, however, remained an unsolved problem and has been a subject of recent debates. In this paper we propose a novel model beyond the standard stochastic models of tumor development, in order to explore the effect of the density of the CSCs and oxygen on the tumor’s invasive behavior. The model identifies natural selection as the underlying process for complex morphology of tumors, which has been observed experimentally, and indicates that their invasive behavior depends on both the number of the CSCs and the oxygen density in the microenvironment. The interplay between the external and internal conditions may pave the way for a new cancer therapy.
Methane release from the southern Brazilian margin during the last glacial
Authors: Portilho-Ramos R. C. , Cruz A. P. S. , Barbosa C. F. , Rathburn A. E. , Mulitza S. , Venancio I. M. , Schwenk T. , Rühlemann C. , Vidal L. , Chiessi C. M. , Silveira C. S.
Published: April 2018

Seafloor methane release can significantly affect the global carbon cycle and climate. Appreciable quantities of methane are stored in continental margin sediments as shallow gas and hydrate deposits, and changes in pressure, temperature and/or bottom-currents can liberate significant amounts of this greenhouse gas. Understanding the spatial and temporal dynamics of marine methane deposits and their relationships to environmental change are critical for assessing past and future carbon cycle and climate change. Here we present foraminiferal stable carbon isotope and sediment mineralogy records suggesting for the first time that seafloor methane release occurred along the southern Brazilian margin during the last glacial period (40–20 cal ka BP). Our results show that shallow gas deposits on the southern Brazilian margin responded to glacial−interglacial paleoceanographic changes releasing methane due to the synergy of sea level lowstand, warmer bottom waters and vigorous bottom currents during the last glacial period. High sea level during the Holocene resulted in an upslope shift of the Brazil Current, cooling the bottom waters and reducing bottom current strength, reducing methane emissions from the southern Brazilian margin.
Texture analysis- and support vector machine-assisted diffusional kurtosis imaging may allow in vivo gliomas grading and IDH-mutation status prediction: a preliminary study
Authors: Bisdas Sotirios , Shen Haocheng , Thust Steffi , Katsaros Vasileios , Stranjalis George , Boskos Christos , Brandner Sebastian , Zhang Jianguo
Published: April 2018

We sought to investigate, whether texture analysis of diffusional kurtosis imaging (DKI) enhanced by support vector machine (SVM) analysis may provide biomarkers for gliomas staging and detection of the IDH mutation. First-order statistics and texture feature extraction were performed in 37 patients on both conventional (FLAIR) and mean diffusional kurtosis (MDK) images and recursive feature elimination (RFE) methodology based on SVM was employed to select the most discriminative diagnostic biomarkers. The first-order statistics demonstrated significantly lower MDK values in the IDH-mutant tumors. This resulted in 81.1% accuracy (sensitivity = 0.96, specificity = 0.45, AUC 0.59) for IDH mutation diagnosis. There were non-significant differences in average MDK and skewness among the different tumour grades. When texture analysis and SVM were utilized, the grading accuracy achieved by DKI biomarkers was 78.1% (sensitivity 0.77, specificity 0.79, AUC 0.79); the prediction accuracy for IDH mutation reached 83.8% (sensitivity 0.96, specificity 0.55, AUC 0.87). For the IDH mutation task, DKI outperformed significantly the FLAIR imaging. When using selected biomarkers after RFE, the prediction accuracy achieved 83.8% (sensitivity 0.92, specificity 0.64, AUC 0.88). These findings demonstrate the superiority of DKI enhanced by texture analysis and SVM, compared to conventional imaging, for gliomas staging and prediction of IDH mutational status.
Consistent differences in fitness traits across multiple generations of Olympia oysters
Authors: Silliman Katherine E. , Bowyer Tynan K. , Roberts Steven B.
Published: April 2018

Adaptive evolution and plasticity are two mechanisms that facilitate phenotypic differences between populations living in different environments. Understanding which mechanism underlies variation in fitness-related traits is a crucial step in designing conservation and restoration management strategies for taxa at risk from anthropogenic stressors. Olympia oysters (Ostrea lurida) have received considerable attention with regard to restoration, however there is limited information on adaptive population structure. Using oysters raised under common conditions for up to two generations (F1s and F2s), we tested for evidence of divergence in reproduction, larval growth, and juvenile growth among three populations in Puget Sound, Washington. We found that the population with the fastest growth rate also exhibited delayed and reduced reproductive activity, indicating a potential adaptive trade-off. Our results corroborate and extend upon a previous reciprocal transplant study on F1 oysters from the same populations, indicating that variation in growth rate and differences in reproductive timing are consistent across both natural and laboratory environments and have a strongly heritable component that cannot be entirely attributed to plasticity.
Alterations in the health of hibernating bats under pathogen pressure
Authors: Bandouchova Hana , Bartonička Tomáš , Berkova Hana , Brichta Jiri , Kokurewicz Tomasz , Kovacova Veronika , Linhart Petr , Piacek Vladimir , Pikula Jiri , Zahradníková Alexandra , Zukal Jan
Published: April 2018

In underground hibernacula temperate northern hemisphere bats are exposed to Pseudogymnoascus destructans, the fungal agent of white-nose syndrome. While pathological and epidemiological data suggest that Palearctic bats tolerate this infection, we lack knowledge about bat health under pathogen pressure. Here we report blood profiles, along with body mass index (BMI), infection intensity and hibernation temperature, in greater mouse-eared bats (Myotis myotis). We sampled three European hibernacula that differ in geomorphology and microclimatic conditions. Skin lesion counts differed between contralateral wings of a bat, suggesting variable exposure to the fungus. Analysis of blood parameters suggests a threshold of ca. 300 skin lesions on both wings, combined with poor hibernation conditions, may distinguish healthy bats from those with homeostatic disruption. Physiological effects manifested as mild metabolic acidosis, decreased glucose and peripheral blood eosinophilia which were strongly locality-dependent. Hibernating bats displaying blood homeostasis disruption had 2 °C lower body surface temperatures. A shallow BMI loss slope with increasing pathogen load suggested a high degree of infection tolerance. European greater mouse-eared bats generally survive P. destructans invasion, despite some health deterioration at higher infection intensities (dependant on hibernation conditions). Conservation measures should minimise additional stressors to conserve constrained body reserves of bats during hibernation.
A quantitative LumiFluo assay to test inhibitory compounds blocking p53 degradation induced by human papillomavirus oncoprotein E6 in living cells
Authors: Messa Lorenzo , Celegato Marta , Bertagnin Chiara , Mercorelli Beatrice , Nannetti Giulio , Palù Giorgio , Loregian Arianna
Published: April 2018

High-risk human papillomaviruses (HR-HPVs) are the causative agents for the onset of several epithelial cancers in humans. The deregulated expression of the viral oncoproteins E6 and E7 is the driving force sustaining the progression of malignant transformation in pre-neoplastic lesions. Targeting the viral E6 oncoprotein through inhibitory compounds can counteract the survival of cancer cells due to the reactivation of p53-mediated pathways and represents an intriguing strategy to treat HPV-associated neoplasias. Here, we describe the development of a quantitative and easy-to-perform assay to monitor the E6-mediated degradation of p53 in living cells to be used for small-molecule testing. This assay allows to unbiasedly determine whether a compound can protect p53 from the E6-mediated degradation in cells, through a simple 3-step protocol. We validated the assay by testing two small molecules, SAHA and RITA, reported to impair the E6-mediated p53 degradation. Interestingly, we observed that only SAHA efficiently rescued p53, while RITA could not provide the same degree of protection. The possibility to specifically and quantitatively monitor the ability of a selected compound to rescue p53 in a cellular context through our LumiFluo assay could represent an important step towards the successful development of anti-HPV drugs.
Lignin peroxidase ligand access channel dysfunction in the presence of atrazine
Authors: Ecker János , Fülöp László
Published: April 2018

Studies have determined that the white-rot basidiomycete Phanerochaete chrysosporium is capable of biodegrading the atrazine herbicide with its broad-specificity enzymes, but the particular role of biocatalysts is still unclear. In the case of lignin peroxidase, a ligand access channel connected to the active heme cofactor provides access to the active site for potential small-sized substrates. Experimental results show that lignin peroxidase is unable to degrade atrazine, therefore, the primary goal was to determine whether there is any connection between the structural and dynamical properties of the enzyme and its incapability to degrade atrazine. The results of protein-ligand docking and molecular dynamics study correlate with relevant, published NMR and molecular dynamics data, and give the answer to the lack of atrazine degradation by lignin peroxidase which has already been established by numerous authors using experimental methods. Atrazine has no access to heme edge due to the electric charges of the delocalized s-triazine ring. The detected phenomenon suggests that the small size of the ligands only is not a sufficient condition to access the active site. Their physicochemical properties influence the structural behaviour of the channel.
Towards a generalized toxicity prediction model for oxide nanomaterials using integrated data from different sources
Authors: Choi Jang-Sik , Ha My Kieu , Trinh Tung Xuan , Yoon Tae Hyun , Byun Hyung-Gi
Published: April 2018

A generalized toxicity classification model for 7 different oxide nanomaterials is presented in this study. A data set extracted from multiple literature sources and screened by physicochemical property based quality scores were used for model development. Moreover, a few more preprocessing techniques, such as synthetic minority over-sampling technique, were applied to address the imbalanced class problem in the data set. Then, classification models using four different algorithms, such as generalized linear model, support vector machine, random forest, and neural network, were developed and their performances were compared to find the best performing preprocessing methods as well as algorithms. The neural network model built using the balanced data set was identified as the model with best predictive performance, while applicability domain was defined using k-nearest neighbours algorithm. The analysis of relative attribute importance for the built neural network model identified dose, formation enthalpy, exposure time, and hydrodynamic size as the four most important attributes. As the presented model can predict the toxicity of the nanomaterials in consideration of various experimental conditions, it has the advantage of having a broader and more general applicability domain than the existing quantitative structure-activity relationship model.
p52 expression enhances lung cancer progression
Authors: Saxon Jamie A. , Yu Hui , Polosukhin Vasiliy V. , Stathopoulos Georgios T. , Gleaves Linda A. , McLoed Allyson G. , Massion Pierre P. , Yull Fiona E. , Zhao Zhongming , Blackwell Timothy S.
Published: April 2018

While many studies have demonstrated that canonical NF-κB signaling is a central pathway in lung tumorigenesis, the role of non-canonical NF-κB signaling in lung cancer remains undefined. We observed frequent nuclear accumulation of the non-canonical NF-κB component p100/p52 in human lung adenocarcinoma. To investigate the impact of non-canonical NF-κB signaling on lung carcinogenesis, we employed transgenic mice with doxycycline-inducible expression of p52 in airway epithelial cells. p52 over-expression led to increased tumor number and progression after injection of the carcinogen urethane. Gene expression analysis of lungs from transgenic mice combined within vitrostudies suggested that p52 promotes proliferation of lung epithelial cells through regulation of cell cycle-associated genes. Using gene expression and patient information from The Cancer Genome Atlas (TCGA) database, we found that expression of p52-associated genes was increased in lung adenocarcinomas and correlated with reduced survival, even in early stage disease. Analysis of p52-associated gene expression in additional human lung adenocarcinoma datasets corroborated these findings. Together, these studies implicate the non-canonical NF-κB component p52 in lung carcinogenesis and suggest modulation of p52 activity and/or downstream mediators as new therapeutic targets.
Indistinguishability as nonlocality constraint
Authors: Amorim Cássio Sozinho
Published: April 2018

A physical explanation for quantum bounds to nonlocality (Tsirelson’s bound) is a fundamental problem in quantum theory, for it is known that no-signaling alone fails to reproduce this limit. Here, information indistinguishability is presented as the indistinguishability of qubits or more general bits, and it suggests an answer to the nonlocality conundrum, ultimately placing it as the origin to quantum limits. Indistinguishability is also connected to exclusivity principle, and it is shown that indistinguishability leads to quantum correlation bounds. This suggests indistinguishability be as fundamental as non-locality and relativistic causality for nonlocal realism.
Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women
Authors: Grindler N. M. , Vanderlinden L. , Karthikraj R. , Kannan K. , Teal S. , Polotsky A. J. , Powell T. L. , Yang I. V. , Jansson T.
Published: April 2018

Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.
Increased Abundance and Nursery Habitat Use of the Bull Shark (Carcharhinus leucas) in Response to a Changing Environment in a Warm-Temperate Estuary
Authors: Bangley Charles W. , Paramore Lee , Shiffman David S. , Rulifson Roger A.
Published: April 2018

A general northward shift in marine species distributions has been observed in the western North Atlantic Ocean, which may have significant ecological consequences. Large coastal sharks can have wide migratory distributions but show fidelity to specific nursery habitats. Here we show evidence for nursery range expansion into Pamlico Sound, North Carolina by a marine apex predator, the Bull Shark (Carcharhinus leucas). Previous assessments have shown little to no use of estuarine North Carolina waters as nursery habitat by Bull Sharks from 1965–2011. Juvenile sharks were rarely captured in a fishery-independent gillnet survey conducted by the North Carolina Division of Marine Fisheries (NCDMF) from 2003–2011, but were present every year from 2011–2016. Juvenile Bull Shark presence in the Sound was strongly related to early summer temperatures and late summer salinities, which have increased in the estuary over the 13 survey years, and further evidence for increasing water temperatures in Pamlico Sound was found in a 45-year data set for the NCDMF estuarine trawl survey. These results suggest that increasing water temperature and salinity have allowed Bull Sharks to expand their nursery habitat. This shift will have unknown, but potentially strong, impacts on both the local ecosystem and interactions with humans.
Expression of KK-LC-1, a cancer/testis antigen, at non-tumour sites of the stomach carrying a tumour
Authors: Fukuyama Takashi , Futawatari Nobue , Yamamura Rui , Yamazaki Taiga , Ichiki Yoshinobu , Ema Akira , Ushiku Hideki , Nishi Yatsushi , Takahashi Yoshihito , Otsuka Toshikazu , Yamazaki Hitoshi , Koizumi Wasaburo , Yasumoto Kosei , Kobayashi Noritada
Published: April 2018

Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) and predominant target for cancer immunotherapy. Our previous study indicated that KK-LC-1 was expressed in 82% of gastric cancers, and also in 79% of early stage of gastric cancers, with a correlation to Helicobacter pylori (H. pylori) infection. In addition, we found that KK-LC-1 was occasionally expressed at non-tumour sites of stomachs carrying tumours. Here, we investigated the characteristics of KK-LC-1 expression at non-tumour sites and the clinical utility of these phenomena. The gene expression of KK-LC-1 was detected at the non-tumour sites including pyloric glands. The most detectable corpus/gland subset had a KK-LC-1 expression rate of 77% in the pyloric gland of the lower corpus where H. pylori preferentially exists. KK-LC-1 expression rates were 67% or 32% with or without intestinal metaplasia, which also induced by H. pylori, respectively. Consequently, KK-LC-1 would be detected at the pre-cancerous condition of the stomach, and may be a useful marker to predict gastric cancer.
Optical Coherence Tomography Angiography Vessel Density Changes after Acute Intraocular Pressure Elevation
Authors: Zhang Qi , Jonas Jost B. , Wang Qian , Chan Szy Yann , Xu Liang , Wei Wen Bin , Wang Ya Xing
Published: April 2018

To investigate changes in retinal vessel density in optic nerve head (ONH) and macula after acute intraocular pressure (IOP) elevation, we conducted a prospective observational study. Eyes with IOP rise ≥5 mmHg after 2-hour dark room prone provocative test (DRPPT) were included. Vasculature of ONH and macula was examined by optical coherence tomography angiography (OCTA) at baseline and after DRPPT. Among the 65 eyes of 42 individuals, 40 eyes with qualified images were enrolled. Mean IOP rise was 9.6 ± 4.2 mmHg (5.0–23.3 mmHg) after DRPPT. Retinal vessel density did not differ after IOP rise for either the papillary region (optic nerve head and radial peripapillary capillary layer) or the macula region (superficial, deep and outer retinal layer) (P > 0.05). Vessel density in each subregion did not change either. If only enrolled eyes with IOP rise ≥10 mmHg, similar results were obtained in condition of IOP increase by 15.0 ± 3.6 mmHg. To conclude, eyes with an acute IOP elevation by 10 or 15 mmHg for two hours, while the blood pressure remained constant, the vessel density in both ONH and macula region examined by OCTA did not show significant changes. The observations fit with an IOP-related autoregulation in retinal blood flow for a moderate elevation of IOP.
Aligned contiguous microfiber platform enhances neural differentiation of embryonic stem cells
Authors: Liu Zhenjie , Hu Zhengqing
Published: April 2018

A microfiber platform that is able to enhance neuronal differentiation and guide aligned neurite outgrowths is essential to the repair of nerve damage. To achieve this aim, we utilized biocompatible and biodegradable poly lactic-co-glycolic acid (PLGA) to design a novel Aligned Contiguous Microfiber Platform (ACMFP) as substrates for the neuronal induction of mouse embryonic stem (ES) cells. To generate the ACMFP, a modified micro-fluid chip system was established to control microfiber parameters including fiber diameter, alignment, and the distance between fibers. Further, Pluronic-F127 was applied to the ACMFP system to maintain a stable and highly aligned fiber platform for at least 12 days. We found that the ACMFP can enhance the neuronal differentiation of mouse ES cells. The ACMFP system showed significantly better neurite outgrowth alignment guidance compared to the control substrate. The effects of alignment guidance were inversely proportionate to the diameter of the fiber, with the optimal diameter size of 60 µm. This study demonstrates a novel ACMFP system that can be used as a biomaterial substrate for neurite outgrowth alignment guidance, which may provide a new model for the development of a multidisciplinary treatment option for nerve injuries.
Increasing thermal stress for tropical coral reefs: 1871–2017
Authors: Lough J. M. , Anderson K. D. , Hughes T. P.
Published: April 2018

Tropical corals live close to their upper thermal limit making them vulnerable to unusually warm summer sea temperatures. The resulting thermal stress can lead to breakdown of the coral-algal symbiosis, essential for the functioning of reefs, and cause coral bleaching. Mass coral bleaching is a modern phenomenon associated with increases in reef temperatures due to recent global warming. Widespread bleaching has typically occurred during El Niño events. We examine the historical level of stress for 100 coral reef locations with robust bleaching histories. The level of thermal stress (based on a degree heating month index, DHMI) at these locations during the 2015–2016 El Niño was unprecedented over the period 1871–2017 and exceeded that of the strong 1997–1998 El Niño. The DHMI was also 5 times the level of thermal stress associated with the ‘pre-industrial’, 1877–1878, El Niño. Coral reefs have, therefore, already shown their vulnerability to the modest (~0.92 °C) global warming that has occurred to date. Estimates of future levels of thermal stress suggest that even the optimistic 1.5 °C Paris Agreement target is insufficient to prevent more frequent mass bleaching events for the world’s reefs. Effectively, reefs of the future will not be the same as those of the past.
Regulatory T cell-derived extracellular vesicles modify dendritic cell function
Authors: Tung Sim L. , Boardman Dominic A. , Sen Monica , Letizia Marilena , Peng Qi , Cianci Nicole , Dioni Laura , Carlin Leo M. , Lechler Robert , Bollati Valentina , Lombardi Giovanna , Smyth Lesley A.
Published: April 2018

Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs. In particular two miRNAs, namely miR-150-5p and miR-142-3p, were increased in DCs following their interaction with Tregs and Treg derived exosomes. One of the consequences for DCs following the acquisition of miRNAs contained in Treg derived EVs was the induction of a tolerogenic phenotype in these cells, with increased IL-10 and decreased IL-6 production being observed following LPS stimulation. Altogether our findings provide data to support the idea that intercellular transfer of miRNAs via EVs may be a novel mechanism by which Tregs regulate DC function and could represent a mechanism to inhibit immune reactions in tissues.
Cortical Classification with Rhythm Entropy for Error Processing in Cocktail Party Environment Based on Scalp EEG Recording
Authors: Tian Yin , Xu Wei , Yang Li
Published: April 2018

Using single-trial cortical signals calculated by weighted minimum norm solution estimation (WMNE), the present study explored a feature extraction method based on rhythm entropy to classify the scalp electroencephalography (EEG) signals of error response from that of correct response during performing auditory-track tasks in cocktail party environment. The classification rate achieved 89.7% with single-trial (≈700 ms) when using support vector machine(SVM) with the leave-one-out-cross-validation (LOOCV). And high discriminative regions mainly distributed at the medial frontal cortex (MFC), the left supplementary motor area (lSMA) and the right supplementary motor area (rSMA). The mean entropy value for error trials was significantly lower than that for correct trials in the discriminative cortices. By time-varying network analysis, different information flows changed among these discriminative regions with time, i.e. error processing showed a left-bias information flow, and correct processing presented a right-bias information flow. These findings revealed that the rhythm information based on single cortical signals could be well used to describe characteristics of error-related EEG signals and further provided a novel application about auditory attention for brain computer interfaces (BCIs).