bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization and Classification of Paddy Field Pests using a Saliency Map and Deep Convolutional Neural Network
Authors: Liu Ziyi , Gao Junfeng , Yang Guoguo , Zhang Huan , He Yong
Published: February 2016

We present a pipeline for the visual localization and classification of agricultural pest insects by computing a saliency map and applying deep convolutional neural network (DCNN) learning. First, we used a global contrast region-based approach to compute a saliency map for localizing pest insect objects. Bounding squares containing targets were then extracted, resized to a fixed size and used to construct a large standard database calledPest ID. This database was then utilized for self-learning of local image features which were, in turn, used for classification by DCNN. DCNN learning optimized the critical parameters, including size, number and convolutional stride of local receptive fields, dropout ratio and the final loss function. To demonstrate the practical utility of using DCNN, we explored different architectures by shrinking depth and width and found effective sizes that can act as alternatives for practical applications. On the test set of paddy field images, our architectures achieved a mean Accuracy Precision (mAP) of 0.951, a significant improvement over previous methods.
Novel electronic ferroelectricity in an organic charge-order insulator investigated with terahertz-pump optical-probe spectroscopy
Authors: Yamakawa H. , Miyamoto T. , Morimoto T. , Yada H. , Kinoshita Y. , Sotome M. , Kida N. , Yamamoto K. , Iwano K. , Matsumoto Y. , Watanabe S. , Shimoi Y. , Suda M. , Yamamoto H. M. , Mori H. , Okamoto H.
Published: February 2016

In electronic-type ferroelectrics, where dipole moments produced by the variations of electron configurations are aligned, the polarization is expected to be rapidly controlled by electric fields. Such a feature can be used for high-speed electric-switching and memory devices. Electronic-type ferroelectrics include charge degrees of freedom, so that they are sometimes conductive, complicating dielectric measurements. This makes difficult the exploration of electronic-type ferroelectrics and the understanding of their ferroelectric nature. Here, we show unambiguous evidence for electronic ferroelectricity in the charge-order (CO) phase of a prototypical ET-based molecular compound, α-(ET)2I3 (ET:bis(ethylenedithio)tetrathiafulvalene), using a terahertz pulse as an external electric field. Terahertz-pump second-harmonic-generation(SHG)-probe and optical-reflectivity-probe spectroscopy reveal that the ferroelectric polarization originates from intermolecular charge transfers and is inclined 27° from the horizontal CO stripe. These features are qualitatively reproduced by the density-functional-theory calculation. After sub-picosecond polarization modulation by terahertz fields, prominent oscillations appear in the reflectivity but not in the SHG-probe results, suggesting that the CO is coupled with molecular displacements, while the ferroelectricity is electronic in nature. The results presented here demonstrate that terahertz-pump optical-probe spectroscopy is a powerful tool not only for rapidly controlling polarizations, but also for clarifying the mechanisms of ferroelectricity.
Potential diagnostic value of serum/pleural fluid IL-31 levels for tuberculous pleural effusion
Authors: Gao Yan , Ou Qinfang , Wu Jing , Zhang Bingyan , Shen Lei , Chen Shaolong , Weng Xinhua , Zhang Ying , Zhang Wenhong , Shao Lingyun
Published: February 2016

The aim of this study was to explore the diagnostic value of IL-31 levels in the pleural fluid and plasma to differentially diagnose tuberculous and malignant pleural effusion. We enrolled 91 cases, including tuberculous pleural effusion (TPE, n = 50), malignant pleural effusion (MPE, n = 41), other cases including pneumonia with pleural fluid, pulmonary tuberculosis and healthy people as controls. Whole blood was stimulated with the M. tuberculosis–specific antigens and plasma was collected. The multiplex bead-based cytokine immunoassay was employed to measure the levels of various cytokines. IL-31 was found to be the most prominent cytokine (P < 0.0001) and with an optimal cut-off value of 67.5 pg/mL, the sensitivity and specificity for the diagnosis of TPE were 86% and 100%, respectively. Furthermore, the tuberculosis-specific IL-31 levels in the plasma of TPE patients were higher than that of MPE patients (P = 0.0002). At an optimal cut-off value of 23.9 pg/mL, the sensitivity and specificity for the diagnosis of TPE were 92.9% and 85.7%, respectively. Ultimately, the combination of pleural fluid with the plasma tuberculosis-specific IL-31 levels improved the sensitivity and specificity to 94.0% and 95.1%, respectively. Thus, we identified a novel biomarker for the diagnosis of TPE for clinical application.
Alp7/TACC-Alp14/TOG generates long-lived, fast-growing MTs by an unconventional mechanism
Authors: Hussmann Frauke , Drummond Douglas R. , Peet Daniel R. , Martin Douglas S. , Cross Robert A.
Published: February 2016

Alp14 is a TOG-family microtubule polymerase from S. pombe that tracks plus ends and accelerates their growth. To interrogate its mechanism, we reconstituted dynamically unstable single isoform S. pombe microtubules with full length Alp14/TOG and Alp7, the TACC-family binding partner of Alp14. We find that Alp14 can drive microtubule plus end growth at GTP-tubulin concentrations at least 10-fold below the usual critical concentration, at the expense of increased catastrophe. This reveals Alp14 to be a highly unusual enzyme that biases the equilibrium for the reaction that it catalyses. Alp7/TACC enhances the effectiveness of Alp14, by increasing its occupancy. Consistent with this, we show in live cells that Alp7 deletion produces very similar MT dynamics defects to Alp14 deletion. The ability of Alp7/14 to accelerate and bias GTP-tubulin exchange at microtubule plus ends allows it to generate long-lived, fast-growing microtubules at very low cellular free tubulin concentrations.
Genome-guided Investigation of Antibiotic Substances produced by Allosalinactinospora lopnorensis CA15-2T from Lop Nor region, China
Authors: Huang Chen , Leung Ross Ka-Kit , Guo Min , Tuo Li , Guo Lin , Yew Wing Wai , Lou Inchio , Lee Simon Ming Yuen , Sun Chenghang
Published: February 2016

Microbial secondary metabolites are valuable resources for novel drug discovery. In particular, actinomycetes expressed a range of antibiotics against a spectrum of bacteria. In genus level, strain Allosalinactinospora lopnorensis CA15-2T is the first new actinomycete isolated from the Lop Nor region, China. Antimicrobial assays revealed that the strain could inhibit the growth of certain types of bacteria, including Acinetobacter baumannii and Staphylococcus aureus, highlighting its clinical significance. Here we report the 5,894,259 base pairs genome of the strain, containing 5,662 predicted genes, and 832 of them cannot be detected by sequence similarity-based methods, suggesting the new species may carry a novel gene pool. Furthermore, our genome-mining investigation reveals that A. lopnorensis CA15-2T contains 17 gene clusters coding for known or novel secondary metabolites. Meanwhile, at least six secondary metabolites were disclosed from ethyl acetate (EA) extract of the fermentation broth of the strain by high-resolution UPLC-MS. Compared with reported clusters of other species, many new genes were found in clusters, and the physical chromosomal location and order of genes in the clusters are distinct. This study presents evidence in support of A. lopnorensis CA15-2T as a potent natural products source for drug discovery.
Metabolic disruption identified in the Huntington’s disease transgenic sheep model
Authors: Handley Renee. R. , Reid Suzanne J. , Patassini Stefano , Rudiger Skye R. , Obolonkin Vladimir , McLaughlan Clive. J. , Jacobsen Jessie C. , Gusella James F. , MacDonald Marcy E. , Waldvogel Henry J. , Bawden C. Simon , Faull Richard L. M. , Snell Russell G.
Published: February 2016

Huntington’s disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease.
Mirror-symmetry protected non-TRIM surface state in the weak topological insulator Bi2TeI
Authors: Rusinov I. P. , Menshchikova T. V. , Isaeva A. , Eremeev S. V. , Koroteev Yu. M. , Vergniory M. G. , Echenique P. M. , Chulkov E. V.
Published: February 2016

Strong topological insulators (TIs) support topological surfaces states on any crystal surface. In contrast, a weak, time-reversal-symmetry-driven TI with at least one non-zero v1, v2, v3 ℤ2 index should host spin-locked topological surface states on the surfaces that are not parallel to the crystal plane with Miller indices (v1 v2 v3). On the other hand, mirror symmetry can protect an even number of topological states on the surfaces that are perpendicular to a mirror plane. Various symmetries in a bulk material with a band inversion can independently preordain distinct crystal planes for realization of topological states. Here we demonstrate the first instance of coexistence of both phenomena in the weak 3D TI Bi2TeI which (v1 v2 v3) surface hosts a gapless spin-split surface state protected by the crystal mirror-symmetry. The observed topological state has an even number of crossing points in the "Equation missing" directions of the 2D Brillouin zone due to a non-TRIM bulk-band inversion. Our findings shed light on hitherto uncharted features of the electronic structure of weak topological insulators and open up new vistas for applications of these materials in spintronics.
Selective binding modes and allosteric inhibitory effects of lupane triterpenes on protein tyrosine phosphatase 1B
Authors: Jin Tiantian , Yu Haibo , Huang Xu-Feng
Published: February 2016

Protein Tyrosine Phosphatase 1B (PTP1B) has been recognized as a promising therapeutic target for treating obesity, diabetes, and certain cancers for over a decade. Previous drug design has focused on inhibitors targeting the active site of PTP1B. However, this has not been successful because the active site is positively charged and conserved among the protein tyrosine phosphatases. Therefore, it is important to develop PTP1B inhibitors with alternative inhibitory strategies. Using computational studies including molecular docking, molecular dynamics simulations, and binding free energy calculations, we found that lupane triterpenes selectively inhibited PTP1B by targeting its more hydrophobic and less conserved allosteric site. These findings were verified using two enzymatic assays. Furthermore, the cell culture studies showed that lupeol and betulinic acid inhibited the PTP1B activity stimulated by TNFα in neurons. Our study indicates that lupane triterpenes are selective PTP1B allosteric inhibitors with significant potential for treating those diseases with elevated PTP1B activity.
Genomic study of the Ket: a Paleo-Eskimo-related ethnic group with significant ancient North Eurasian ancestry
Authors: Flegontov Pavel , Changmai Piya , Zidkova Anastassiya , Logacheva Maria D. , Altınışık N. Ezgi , Flegontova Olga , Gelfand Mikhail S. , Gerasimov Evgeny S. , Khrameeva Ekaterina E. , Konovalova Olga P. , Neretina Tatiana , Nikolsky Yuri V. , Starostin George , Stepanova Vita V. , Travinsky Igor V. , Tříska Martin , Tříska Petr , Tatarinova Tatiana V.
Published: February 2016

The Kets, an ethnic group in the Yenisei River basin, Russia, are considered the last nomadic hunter-gatherers of Siberia and Ket language has no transparent affiliation with any language family. We investigated connections between the Kets and Siberian and North American populations, with emphasis on the Mal’ta and Paleo-Eskimo ancient genomes, using original data from 46 unrelated samples of Kets and 42 samples of their neighboring ethnic groups (Uralic-speaking Nganasans, Enets and Selkups). We genotyped over 130,000 autosomal SNPs, identified mitochondrial and Y-chromosomal haplogroups and performed high-coverage genome sequencing of two Ket individuals. We established that Nganasans, Kets, Selkups and Yukaghirs form a cluster of populations most closely related to Paleo-Eskimos in Siberia (not considering indigenous populations of Chukotka and Kamchatka). Kets are closely related to modern Selkups and to some Bronze and Iron Age populations of the Altai region, with all these groups sharing a high degree of Mal’ta ancestry. Implications of these findings for the linguistic hypothesis uniting Ket and Na-Dene languages into a language macrofamily are discussed.
Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty
Authors: Ohashi Rie , Takao Keizo , Miyakawa Tsuyoshi , Shiina Nobuyuki
Published: February 2016

RNG105 (also known as Caprin1) is a major RNA-binding protein in neuronal RNA granules and is responsible for mRNA transport to dendrites and neuronal network formation. A recent study reported that a heterozygous mutation in the Rng105 gene was found in an autism spectrum disorder (ASD) patient, but it remains unclear whether there is a causal relation between RNG105 deficiency and ASD. Here, we subjected Rng105+/− mice to a comprehensive behavioral test battery and revealed the influence of RNG105 deficiency on mouse behavior. Rng105+/− mice exhibited a reduced sociality in a home cage and a weak preference for social novelty. Consistently, the Rng105+/− mice also showed a weak preference for novel objects and novel place patterns. Furthermore, although the Rng105+/− mice exhibited normal memory acquisition, they tended to have relative difficulty in reversal learning in the spatial reference tasks. These findings suggest that the RNG105 heterozygous knockout leads to a reduction in sociality, response to novelty and flexibility in learning, which are implicated in ASD-like behavior.
Health Habits of Employees in a Large Medical Center: Time Trends and Impact of a Worksite Wellness Facility
Authors: Abu Dabrh Abd Moain , Gorty Archana , Jenkins Sarah M. , Murad Mohammad Hassan , Hensrud Donald D.
Published: February 2016

Worksite health interventions are not novel but their effect remains subject of debate. We examined employer-based wellness program to determine health habits trends, and compare prevalence estimates to national data. We conducted serial surveys (1996 and 2007–10) to employees of a large medical center that included questions measuring outcomes, including obesity, regular exercise, cardiovascular activity, and smoking status. Logistic regression models were estimated to compare data by membership across years, considering p-values ≤ 0.01 as statistically significant. 3,206 employees responded (Response rates 59–68%). Obesity prevalence increased over time in members and nonmembers of the wellness facility, consistent with national trends. Members had a lower prevalence of cigarette smoking compared to nonmembers (overall year-adjusted odds ratio 0.66, P < 0.001). Further, employees had a lower prevalence of cigarette smoking (9.7 vs. 17.3% in 2010, P < 0.001) compared with national data. Wellness facility membership was associated with increased regular exercise and cardiovascular exercise (P < 0.001) compared to nonmembers. In summary, working in a medical center was associated with a decreased prevalence of cigarette smoking, but not with lower prevalence of obesity. Worksite wellness facility membership was associated with increased exercise and decreased cigarette smoking. Employer-based interventions may be effective in improving some health behaviors.
The Tactile Window to Consciousness is Characterized by Frequency-Specific Integration and Segregation of the Primary Somatosensory Cortex
Authors: Frey Julia Natascha , Ruhnau Philipp , Leske Sabine , Siegel Markus , Braun Christoph , Weisz Nathan
Published: February 2016

We recently proposed that besides levels of local cortical excitability, also distinct pre-stimulus network states (windows to consciousness) determine whether a near-threshold stimulus will be consciously perceived. In the present magnetoencephalography study, we scrutinised these pre-stimulus network states with a focus on the primary somatosensory cortex. For this purpose participants performed a simple near-threshold tactile detection task. Confirming previous studies, we found reduced alpha and beta power in the somatosensory region contralateral to stimulation prior to correct stimulus detection as compared to undetected stimuli and stronger event-related responses following successful stimulus detection. As expected, using graph theoretical measures, we also observed modulated pre-stimulus network level integration. Specifically, the right primary somatosensory cortex contralateral to stimulation showed an increased integration in the theta band and additionally, a decreased integration in the beta band. Overall, these results underline the importance of network states for enabling conscious perception. Moreover, they indicate that also a reduction of irrelevant functional connections contributes to the window to consciousness by tuning pre-stimulus pathways of information flow.
Microbial communities affecting albumen photography heritage: a methodological survey
Authors: Puškárová Andrea , Bučková Mária , Habalová Božena , Kraková Lucia , Maková Alena , Pangallo Domenico
Published: February 2016

This study is one of the few investigations which analyze albumen prints, perhaps the most important photographic heritage of the late 19thand early 20thcenturies. The chemical composition of photographic samples was assessed using Fourier-transform infrared spectroscopy and X-ray fluorescence. These two non-invasive techniques revealed the complex nature of albumen prints, which are composed of a mixture of proteins, cellulose and salts. Microbial sampling was performed using cellulose nitrate membranes which also permitted the trapped microflora to be observed with a scanning electron microscope. Microbial analysis was performed using the combination of culture-dependent (cultivation in different media, including one 3% NaCl) and culture-independent (bacterial and fungal cloning and sequencing) approaches. The isolated microorganisms were screened for their lipolytic, proteolytic, cellulolytic, catalase and peroxidase activities. The combination of the culture-dependent and -independent techniques together with enzymatic assays revealed a substantial microbial diversity with several deteriogen microorganisms from the generaBacillus,Kocuria,StreptomycesandGeobacillusand the fungal strainsAcrostalagmus luteoalbus,Bjerkandera adusta,Pleurotus pulmonariusandTrichothecium roseum.
Analyzing the Release of Copeptin from the Heart in Acute Myocardial Infarction Using a Transcoronary Gradient Model
Authors: Boeckel Jes-Niels , Oppermann Jana , Anadol Remzi , Fichtlscherer Stephan , Zeiher Andreas M. , Keller Till
Published: February 2016

Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done.
Alternative interpretations for decreasing voltage with increasing charge in ferroelectric capacitors
Authors: Song Seul Ji , Kim Yu Jin , Park Min Hyuk , Lee Young Hwan , Kim Han Joon , Moon Taehwan , Do Kim Keum , Choi Jung-Hae , Chen Zhihui , Jiang Anquan , Hwang Cheol Seong
Published: February 2016

Recent claim on the direct observation of a negative capacitance (NC) effect from a single layer epitaxial Pb(Zr0.2,Ti0.8)O3 (PZT) thin film was carefully reexamined, and alternative interpretations that can explain the experimental results without invoking the NC effect are provided. Any actual ferroelectric capacitor has an interfacial layer, and experiment always measures the sum of voltages across the interface layer and the ferroelectric layer. The main observation of decreasing ferroelectric capacitor voltage (VF) for increasing ferroelectric capacitor charge (QF), claimed to be the direct evidence for the NC effect, could be alternatively interpreted by either the sudden increase in the positive capacitance of a ferroelectric capacitor or decrease in the voltage across the interfacial layer due to resistance degradation. The experimental time-transient VF and QF could be precisely simulated by these alternative models that fundamentally assumes the reverse domain nucleation and growth. Supplementary experiments using an epitaxial BaTiO3 film supported this claim. This, however, does not necessarily mean that the realization of the NC effect within the ferroelectric layer is impractical under appropriate conditions. Rather, the circuit suggested by Khan et al. may not be useful to observe the NC effect directly.
tRNA-Derived Small Non-Coding RNAs in Response to Ischemia Inhibit Angiogenesis
Authors: Li Qing , Hu Bin , Hu Guo-wen , Chen Chun-yuan , Niu Xin , Liu Juan , Zhou Shu-min , Zhang Chang-qing , Wang Yang , Deng Zhi-Feng
Published: February 2016

Ischemic injuries will lead to necrotic tissue damage and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs strikingly increased in the ischemic rat brain. Among these sequences, tRNAVal- and tRNAGly-derived small RNAs account for the most abundant segments. The up-regulation of tRNAVal- and tRNAGly-derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, up-regulation of the tRNAVal- and tRNAGly-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Furthermore, we showed that these small RNAs are generated by angiogenin cleavage. Our results indicate that tRNA-derived fragments are involved in tissue ischemia and we demonstrate for the first time that tRNAVal- and tRNAGly-derived fragments inhibit angiogenesis by modulating the function of endothelial cells.
Seasonal forecasting of lightning and thunderstorm activity in tropical and temperate regions of the world
Authors: Dowdy Andrew J.
Published: February 2016

Thunderstorms are convective systems characterised by the occurrence of lightning. Lightning and thunderstorm activity has been increasingly studied in recent years in relation to the El Niño/Southern Oscillation (ENSO) and various other large-scale modes of atmospheric and oceanic variability. Large-scale modes of variability can sometimes be predictable several months in advance, suggesting potential for seasonal forecasting of lightning and thunderstorm activity in various regions throughout the world. To investigate this possibility, seasonal lightning activity in the world’s tropical and temperate regions is examined here in relation to numerous different large-scale modes of variability. Of the seven modes of variability examined, ENSO has the strongest relationship with lightning activity during each individual season, with relatively little relationship for the other modes of variability. A measure of ENSO variability (the NINO3.4 index) is significantly correlated to local lightning activity at 53% of locations for one or more seasons throughout the year. Variations in atmospheric parameters commonly associated with thunderstorm activity are found to provide a plausible physical explanation for the variations in lightning activity associated with ENSO. It is demonstrated that there is potential for accurately predicting lightning and thunderstorm activity several months in advance in various regions throughout the world.
Mapping forests in monsoon Asia with ALOS PALSAR 50-m mosaic images and MODIS imagery in 2010
Authors: Qin Yuanwei , Xiao Xiangming , Dong Jinwei , Zhang Geli , Roy Partha Sarathi , Joshi Pawan Kumar , Gilani Hammad , Murthy Manchiraju Sri Ramachandra , Jin Cui , Wang Jie , Zhang Yao , Chen Bangqian , Menarguez Michael Angelo , Biradar Chandrashekhar M. , Bajgain Rajen , Li Xiangping , Dai Shengqi , Hou Ying , Xin Fengfei , Moore III Berrien
Published: February 2016

Extensive forest changes have occurred in monsoon Asia, substantially affecting climate, carbon cycle and biodiversity. Accurate forest cover maps at fine spatial resolutions are required to qualify and quantify these effects. In this study, an algorithm was developed to map forests in 2010, with the use of structure and biomass information from the Advanced Land Observation System (ALOS) Phased Array L-band Synthetic Aperture Radar (PALSAR) mosaic dataset and the phenological information from MODerate Resolution Imaging Spectroradiometer (MOD13Q1 and MOD09A1) products. Our forest map (PALSARMOD50 m F/NF) was assessed through randomly selected ground truth samples from high spatial resolution images and had an overall accuracy of 95%. Total area of forests in monsoon Asia in 2010 was estimated to be ~6.3 × 106 km2. The distribution of evergreen and deciduous forests agreed reasonably well with the median Normalized Difference Vegetation Index (NDVI) in winter. PALSARMOD50 m F/NF map showed good spatial and areal agreements with selected forest maps generated by the Japan Aerospace Exploration Agency (JAXA F/NF), European Space Agency (ESA F/NF), Boston University (MCD12Q1 F/NF), Food and Agricultural Organization (FAO FRA) and University of Maryland (Landsat forests), but relatively large differences and uncertainties in tropical forests and evergreen and deciduous forests.
5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas
Authors: Zhang Feng , Liu Yifan , Zhang Zhiwen , Li Jie , Wan Yi , Zhang Liying , Wang Yangmei , Li Xia , Xu Yuqiao , Fu Xin , Zhang Xiumin , Zhang Ming , Zhang Zhekai , Zhang Jing , Yan Qingguo , Ye Jing , Wang Zhe , Chen Charlie Degui , Lin Wei , Li Qing
Published: February 2016

Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5-methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that IDH1 mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA.
Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil-loaded Pluronic P85 Copolymer Micelles
Authors: Zhu Pengxi , Zhao Naping , Sheng Dandan , Hou Jing , Hao Chong , Yang Xue , Zhu Bing , Zhang Shanshan , Han Zhipeng , Wei Lixin , Zhang Li
Published: February 2016

Hepatic metastasis is the leading cause of mortality of colon cancer, which is still lack of an effective therapy. A new delivery system, pluronic P85 block copolymers, conveying chemotherapeutic agent 5-fluorouracil (5-Fu) for inhibiting growth and metastasis of colon cancer was designed and developed. In this study, we demonstrated that 5-Fu produce strong pesticide effect at lower doses in the present of pluronic P85 compared with control groups. The migration and invasion of HCT116 cells and RKO cells were examined and the results showed that migration and invasion capacities of HCT116 cells and RKO cells were reduced by administering 5-Fu/P85 copolymer micelles in vitro and in vivo which indicating an effectively activity. Interestingly, the content of CD133 + CXCR4+ cells in HCT116 cancer cells and RKO cells treated by 5-Fu/P85 copolymer micelles was decreased. Importantly, the epithelial-mesenchymal transition (EMT) of CD133 + CXCR4+ cells, which was strongly associated with liver metastasis of colon cancer, was also suppressed by giving 5-Fu/P85 copolymer micelles. The results indicated that 5-Fu/P85 copolymer micelles could inhibit the growth and metastasis of colon cancer, which could be attributed to the decrease of the content of CD133 + CXCR4+ cells and suppression of EMT of CD133 + CXCR4+ cells.
ATP-containing vesicles in stria vascular marginal cell cytoplasms in neonatal rat cochlea are lysosomes
Authors: Liu Jun , Liu Wenjing , Yang Jun
Published: February 2016

We confirmed that ATP is released from cochlear marginal cells in the stria vascular but the cell organelle in which ATP stores was not identified until now. Thus, we studied the ATP-containing cell organelles and suggest that these are lysosomes. Primary cultures of marginal cells of Sprague-Dawley rats aged 1–3 days was established. Vesicles within marginal cells stained with markers were identified under confocal laser scanning microscope and transmission electron microscope (TEM). Then ATP release from marginal cells was measured after glycyl-L-phenylalanine-ß- naphthylamide (GPN) treatment using a bioluminescent assay. Quinacrine-stained granules within marginal cells were labeled with LysoTracker, a lysosome tracer and lysosomal-associated membrane protein 1(LAMP1), but not labeled with the mitochondrial tracer MitoTracker. Furthermore, LysoTracker-labelled puncta showed accumulation of Mant-ATP, an ATP analog. Treatment with 200 μM GPN quenched fluorescently labeled puncta after incubation with LysoTracker or quinacrine, but not MitoTracker. Quinacrine-labeled organelles observed by TEM were lysosomes and an average 27.7 percent increase in ATP luminescence was observed in marginal cells extracellular fluid after GPN treatment. ATP-containing vesicles in cochlear marginal cells of the stria vascular from neonatal rats are likely lysosomes. ATP release from marginal cells may be via Ca2+-dependent lysosomal exocytosis.
Membrane tubule formation by banana-shaped proteins with or without transient network structure
Authors: Noguchi Hiroshi
Published: February 2016

In living cells, membrane morphology is regulated by various proteins. Many membrane reshaping proteins contain a Bin/Amphiphysin/Rvs (BAR) domain, which consists of a banana-shaped rod. The BAR domain bends the biomembrane along the rod axis and the features of this anisotropic bending have recently been studied. Here, we report on the role of the BAR protein rods in inducing membrane tubulation, using large-scale coarse-grained simulations. We reveal that a small spontaneous side curvature perpendicular to the rod can drastically alter the tubulation dynamics at high protein density, whereas no significant difference is obtained at low density. A percolated network is intermediately formed depending on the side curvature. This network suppresses tubule protrusion, leading to the slow formation of fewer tubules. Thus, the side curvature, which is generated by protein–protein and membrane–protein interactions, plays a significant role in tubulation dynamics. We also find that positive surface tensions and the vesicle membrane curvature can stabilize this network structure by suppressing the tubulation.
Developing genetic tools to exploit Chaetomium thermophilum for biochemical analyses of eukaryotic macromolecular assemblies
Authors: Kellner Nikola , Schwarz Johannes , Sturm Miriam , Fernandez-Martinez Javier , Griesel Sabine , Zhang Wenzhu , Chait Brian T. , Rout Michael P. , Kück Ulrich , Hurt Ed
Published: February 2016

We describe a method to genetically manipulate Chaetomium thermophilum, a eukaryotic thermophile, along with various biochemical applications. The transformation method depends on a thermostable endogenous selection marker operating at high temperatures combined with chromosomal integration of target genes. Our technique allows exploiting eukaryotic thermophiles as source for purifying thermostable native macromolecular complexes with an emphasis on the nuclear pore complex, holding great potential for applications in basic science and biotechnology.
Digital Sorting of Pure Cell Populations Enables Unambiguous Genetic Analysis of Heterogeneous Formalin-Fixed Paraffin-Embedded Tumors by Next Generation Sequencing
Authors: Bolognesi Chiara , Forcato Claudio , Buson Genny , Fontana Francesca , Mangano Chiara , Doffini Anna , Sero Valeria , Lanzellotto Rossana , Signorini Giulio , Calanca Alex , Sergio Maximilian , Romano Rita , Gianni Stefano , Medoro Gianni , Giorgini Giuseppe , Morreau Hans , Barberis Massimo , Corver Willem E. , Manaresi Nicolò
Published: February 2016

Precision medicine in oncology requires an accurate characterization of a tumor molecular profile for patient stratification. Though targeted deep sequencing is an effective tool to detect the presence of somatic sequence variants, a significant number of patient specimens do not meet the requirements needed for routine clinical application. Analysis is hindered by contamination of normal cells and inherent tumor heterogeneity, compounded with challenges of dealing with minute amounts of tissue and DNA damages common in formalin-fixed paraffin-embedded (FFPE) specimens. Here we present an innovative workflow using DEPArray™ system, a microchip-based digital sorter to achieve 100%-pure, homogenous subpopulations of cells from FFPE samples. Cells are distinguished by fluorescently labeled antibodies and DNA content. The ability to address tumor heterogeneity enables unambiguous determination of true-positive sequence variants, loss-of-heterozygosity as well as copy number variants. The proposed strategy overcomes the inherent trade-offs made between sensitivity and specificity in detecting genetic variants from a mixed population, thus rescuing for analysis even the smaller clinical samples with low tumor cellularity.
Task-Specific Balance Training Improves the Sensory Organisation of Balance Control in Children with Developmental Coordination Disorder: A Randomised Controlled Trial
Authors: Fong Shirley S.M. , Guo X. , Liu Karen P.Y. , Ki W.Y. , Louie Lobo H.T. , Chung Raymond C.K. , Macfarlane Duncan J.
Published: February 2016

Sensory organisation of balance control is compromised in children with developmental coordination disorder (DCD). A randomised controlled trial involving 88 children with DCD was conducted to evaluate the efficacy of a task-specific balance training (functional-movement training, FMT) programme in improving balance deficits in a DCD population. The DCD participants were randomly assigned to either a FMT group or a control group. The FMT group received two training sessions/ week for 3 months. Measurements of the participants’ sensory organisation (somatosensory, vestibular and visual ratios), balance and motor proficiency (Movement Assessment Battery for Children, MABC scores) and center of pressure sway velocity (Unilateral Stance Test, UST scores) were taken at baseline, immediately after FMT and 3 months after FMT. The FMT group showed greater improvements than the controls in somatosensory ratio at 3 and 6 months (all P < 0.001), but the within-group changes were not significant (P > 0.05). The results of both the MABC and the UST also indicated that the balance performance of the FMT group was significantly better than that of the control group at 3 and 6 months (all P < 0.05). Task-specific balance training was found to marginally improve the somatosensory function and somewhat improve the balance performance of children with DCD.
Tackling amyloidogenesis in Alzheimer’s disease with A2V variants of Amyloid-β
Authors: Di Fede Giuseppe , Catania Marcella , Maderna Emanuela , Morbin Michela , Moda Fabio , Colombo Laura , Rossi Alessandro , Cagnotto Alfredo , Virgilio Tommaso , Palamara Luisa , Ruggerone Margherita , Giaccone Giorgio , Campagnani Ilaria , Costanza Massimo , Pedotti Rosetta , Salvalaglio Matteo , Salmona Mario , Tagliavini Fabrizio
Published: February 2016

We developed a novel therapeutic strategy for Alzheimer’s disease (AD) exploiting the properties of a natural variant of Amyloid-β (Aβ) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Aβ1-6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Aβ1-6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Aβ toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Aβ1-6A2VTAT(D) inhibits Aβ aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AβA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Aβ1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Aβ production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics.
A genome-wide search for epigenetically regulated genes in zebra finch using MethylCap-seq and RNA-seq
Authors: Steyaert Sandra , Diddens Jolien , Galle Jeroen , De Meester Ellen , De Keulenaer Sarah , Bakker Antje , Sohnius-Wilhelmi Nina , Frankl-Vilches Carolina , Van der Linden Annemie , Van Criekinge Wim , Vanden Berghe Wim , De Meyer Tim
Published: February 2016

Learning and memory formation are known to require dynamic CpG (de)methylation and gene expression changes. Here, we aimed at establishing a genome-wide DNA methylation map of the zebra finch genome, a model organism in neuroscience, as well as identifying putatively epigenetically regulated genes. RNA- and MethylCap-seq experiments were performed on two zebra finch cell lines in presence or absence of 5-aza-2′-deoxycytidine induced demethylation. First, the MethylCap-seq methodology was validated in zebra finch by comparison with RRBS-generated data. To assess the influence of (variable) methylation on gene expression, RNA-seq experiments were performed as well. Comparison of RNA-seq and MethylCap-seq results showed that at least 357 of the 3,457 AZA-upregulated genes are putatively regulated by methylation in the promoter region, for which a pathway analysis showed remarkable enrichment for neurological networks. A subset of genes was validated using Exon Arrays, quantitative RT-PCR and CpG pyrosequencing on bisulfite-treated samples. To our knowledge, this study provides the first genome-wide DNA methylation map of the zebra finch genome as well as a comprehensive set of genes of which transcription is under putative methylation control.
Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster
Authors: Yang Yingying , Su Zhongjing , Song Xuhong , Liang Bin , Zeng Fanxing , Chang Xiaolan , Huang Dongyang
Published: February 2016

The human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene-duplication events. We previously demonstrated that a head-to-head natural antisense transcript (NAT) of DHRS4, denoted DHRS4-AS1, regulates all three genes of the DHRS4 gene cluster. However, it is puzzling that DHRS4L2 and DHRS4L1 did not evolve their own specific NATs to regulate themselves, as it seems both have retained sequences highly homologous to DHRS4-AS1. In a search of the DHRS4-AS1 region for nearby enhancers, we identified an enhancer located 13.8 kb downstream of the DHRS4-AS1 transcriptional start site. We further showed, by using a chromosome conformation capture (3C) assay, that this enhancer is capable of physically interacting with the DHRS4-AS1 promoter through chromosomal looping. The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP. Moreover, the distributions of activating acetyl-H3 and H3K4me3 modifications were found to be greater at the DHRS4-AS1 promoter than at the homologous duplicated regions. We propose that AS1eRNA-driven DNA looping and activating histone modifications promote the expression of DHRS4-AS1 to economically control the DHRS4 gene cluster.
Self-sacrifice Template Formation of Hollow Hetero-Ni7S6/Co3S4 Nanoboxes with Intriguing Pseudo-capacitance for High-performance Electrochemical Capacitors
Authors: Hua Hui , Liu Sijia , Chen Zhiyi , Bao Ruiqi , Shi Yaoyao , Hou Linrui , Pang Gang , Hui Kwun Nam , Zhang Xiaogang , Yuan Changzhou
Published: February 2016

Herein, we report a simple yet efficient self-sacrifice template protocol to smartly fabricate hollow hetero-Ni7S6/Co3S4 nanoboxes (Ni-Co-S NBs). Uniform nickel cobalt carbonate nanocubes are first synthesized as the precursor via solvothermal strategy, and subsequently chemically sulfidized into hollow heter-Ni-Co-S NBs through anion-exchange process. When evaluated as electrode for electrochemical capacitors (ECs), the resultant hetero-Ni-Co-S NBs visually exhibit attractive pesudo-capacitance in KOH just after continuously cyclic voltammetry (CV) scanning for 100 cycles. New insights into the underlying energy-storage mechanism of the hollow hetero-Ni-Co-S electrode, based on physicochemical characterizations and electrochemical evaluation, are first put forward that the electrochemically induced phase transformation gradually occurrs during CV sweep from the hetero-Ni-Co-S to bi-component-active NiOOH and CoOOH, which are the intrinsic charge-storage phases for the appealing Faradaic capacitance (~677 F g−1 at 4 A g−1) of hollow Ni-Co-S NBs at high rates after cycling. When further coupled with negative activated carbon (AC), the AC//hetero-Ni-Co-S asymmetric device with extended electrochemical window of 1.5 V demonstrates high specific energy density of ~31 Wh kg−1. Of significance, we strongly envision that hollow design concept and new findings here hold great promise for enriching synthetic methodologies, and electrochemistry of complex metal sulfides for next-generation ECs.
Characterization of a newly isolated strain Pseudomonas sp. C27 for sulfide oxidation: Reaction kinetics and stoichiometry
Authors: Xu Xi-Jun , Chen Chuan , Guo Hong-liang , Wang Ai-jie , Ren Nan-qi , Lee Duu-Jong
Published: February 2016

Sulfide biooxidation by the novel sulfide-oxidizing bacteria Pseudomonas sp. C27, which could perform autotrophic and heterotrophic denitrification in mixotrophic medium, was studied in batch and continuous systems. Pseudomonas sp. C27 was able to oxidize sulfide at concentrations as high as 17.66 mM. Sulfide biooxidation occurred in two distinct stages, one resulting in the formation of sulfur with nitrate reduction to nitrite, followed by thiosulfate formation with nitrite reduction to N2. The composition of end-products was greatly impacted by the ratio of sulfide to nitrate initial concentrations. At a ratio of 0.23, thiosulfate represented 100% of the reaction products, while only 30% with a ratio of 1.17. In the continuous bioreactor, complete removal of sulfide was observed at sulfide concentration as high as 9.38 mM. Overall sulfide removal efficiency decreased continuously upon further increases in influent sulfide concentrations. Based on the experimental data kinetic parameter values were determined. The value of maximum specific growth rate, half saturation constant, decay coefficient, maintenance coefficient and yield were to be 0.11 h−1, 0.68 mM sulfide, 0.11 h−1, 0.21 mg sulfide/mg biomass h and 0.43 mg biomass/mg sulfide, respectively, which were close to or comparable with those reported in literature by other researches.
Oxidative elemental cycling under the low O2 Eoarchean atmosphere
Authors: Frei Robert , Crowe Sean A. , Bau Michael , Polat Ali , Fowle David A. , Døssing Lasse N.
Published: February 2016

The Great Oxidation Event signals the first large-scale oxygenation of the atmosphere roughly 2.4 Gyr ago. Geochemical signals diagnostic of oxidative weathering, however, extend as far back as 3.3–2.9 Gyr ago. 3.8–3.7 Gyr old rocks from Isua, Greenland stand as a deep time outpost, recording information on Earth’s earliest surface chemistry and the low oxygen primordial biosphere. Here we find fractionated Cr isotopes, relative to the igneous silicate Earth reservoir, in metamorphosed banded iron formations (BIFs) from Isua that indicate oxidative Cr cycling 3.8–3.7 Gyr ago. Elevated U/Th ratios in these BIFs relative to the contemporary crust, also signal oxidative mobilization of U. We suggest that reactive oxygen species were present in the Eoarchean surface environment, under a very low oxygen atmosphere, inducing oxidative elemental cycling during the deposition of the Isua BIFs and possibly supporting early aerobic biology.