bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-of-Flight Three Dimensional Neutron Diffraction in Transmission Mode for Mapping Crystal Grain Structures
Authors: Cereser Alberto , Strobl Markus , Hall Stephen A. , Steuwer Axel , Kiyanagi Ryoji , Tremsin Anton S. , Knudsen Erik B. , Shinohara Takenao , Willendrup Peter K. , da Silva Fanta Alice Bastos , Iyengar Srinivasan , Larsen Peter M. , Hanashima Takayasu , Moyoshi Taketo , Kadletz Peter M. , Krooß Philipp , Niendorf Thomas , Sales Morten , Schmahl Wolfgang W. , Schmidt Søren
Published: August 2017

The physical properties of polycrystalline materials depend on their microstructure, which is the nano- to centimeter scale arrangement of phases and defects in their interior. Such microstructure depends on the shape, crystallographic phase and orientation, and interfacing of the grains constituting the material. This article presents a new non-destructive 3D technique to study centimeter-sized bulk samples with a spatial resolution of hundred micrometers: time-of-flight three-dimensional neutron diffraction (ToF 3DND). Compared to existing analogous X-ray diffraction techniques, ToF 3DND enables studies of samples that can be both larger in size and made of heavier elements. Moreover, ToF 3DND facilitates the use of complicated sample environments. The basic ToF 3DND setup, utilizing an imaging detector with high spatial and temporal resolution, can easily be implemented at a time-of-flight neutron beamline. The technique was developed and tested with data collected at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Complex (J-PARC) for an iron sample. We successfully reconstructed the shape of 108 grains and developed an indexing procedure. The reconstruction algorithms have been validated by reconstructing two stacked Co-Ni-Ga single crystals, and by comparison with a grain map obtained by post-mortem electron backscatter diffraction (EBSD).
Deep Brain Stimulation of the subthalamic nucleus does not negatively affect social cognitive abilities of patients with Parkinson’s disease
Authors: Enrici Ivan , Mitkova Antonia , Castelli Lorys , Lanotte Michele , Lopiano Leonardo , Adenzato Mauro
Published: August 2017

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a treatment option for patients with advanced idiopathic PD successful at alleviating disabling motor symptoms. Nevertheless, the effects of STN-DBS on cognitive functions remain controversial and few studies have investigated modification of social cognitive abilities in patients with PD treated with STN-DBS. Here we expanded the typically-investigated spectrum of these abilities by simultaneously examining emotion recognition, and both affective and cognitive Theory of Mind (ToM). By means of a cross-sectional study, 20 patients with PD under dopaminergic replacement therapy, 18 patients with PD treated with STN-DBS, and 20 healthy controls performed the Ekman 60-Faces test, the full version of the Reading the Mind in the Eyes test, and the Protocol for the Attribution of Communicative Intentions. There were no differences between the PD groups (treated and not treated with STN-DBS) on any of the social cognitive tests. Our results suggest that patients with PD who are treated with STN-DBS do not experience detrimental effects on their social cognitive abilities. The present study, the first one examining a wide spectrum of social cognitive abilities after DBS of the STN, suggests that this surgical procedure can be considered safe from this standpoint.
Rational identification of aggregation hotspots based on secondary structure and amino acid hydrophobicity
Authors: Matsui Daisuke , Nakano Shogo , Dadashipour Mohammad , Asano Yasuhisa
Published: August 2017

Insolubility of proteins expressed in the Escherichia coli expression system hinders the progress of both basic and applied research. Insoluble proteins contain residues that decrease their solubility (aggregation hotspots). Mutating these hotspots to optimal amino acids is expected to improve protein solubility. To date, however, the identification of these hotspots has proven difficult. In this study, using a combination of approaches involving directed evolution and primary sequence analysis, we found two rules to help inductively identify hotspots: the α-helix rule, which focuses on the hydrophobicity of amino acids in the α-helix structure, and the hydropathy contradiction rule, which focuses on the difference in hydrophobicity relative to the corresponding amino acid in the consensus protein. By properly applying these two rules, we succeeded in improving the probability that expressed proteins would be soluble. Our methods should facilitate research on various insoluble proteins that were previously difficult to study due to their low solubility.
DDX3 localizes to the centrosome and prevents multipolar mitosis by epigenetically and translationally modulating p53 expression
Authors: Chen Wei-Ju , Wang Wei-Ting , Tsai Tsung-Yuan , Li Hao-Kang , Lee Yan-Hwa Wu
Published: August 2017

The DEAD-box RNA helicase DDX3 plays divergent roles in tumorigenesis, however, its function in mitosis is unclear. Immunofluorescence indicated that DDX3 localized to centrosome throughout the cell cycle and colocalized with centrosome-associated p53 during mitosis in HCT116 and U2OS cells. DDX3 depletion promoted chromosome misalignment, segregation defects and multipolar mitosis, eventually leading to G2/M delay and cell death. DDX3 prevented multipolar mitosis by inactivation and coalescence of supernumerary centrosomes. DDX3 silencing suppressed Ser15phosphorylation of p53 which is required for p53 centrosomal localization. Additionally, knockout of p53 dramatically diminished the association of DDX3 with centrosome, which was rescued by overexpression of the centrosomal targeting-defective p53 S15A mutant, indicating that centrosomal localization of DDX3 is p53 dependent but not through centrosomal location of p53. Furthermore, DDX3 knockdown suppressedp53transcription through activation of DNA methyltransferases (DNMTs) along with hypermethylation ofp53promoter and promoting the binding of repressive histone marks top53promoter. Moreover, DDX3 modulatedp53mRNA translation. Taken together, our study suggests that DDX3 regulates epigenetic transcriptional and translational activation of p53 and colocalizes with p53 at centrosome during mitosis to ensure proper mitotic progression and genome stability, which supports the tumor-suppressive role of DDX3.
Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage
Authors: Petrucci Vanessa , Chicca Andrea , Glasmacher Sandra , Paloczi Janos , Cao Zongxian , Pacher Pal , Gertsch Jürg
Published: August 2017

Pepcan-12 (RVD-hemopressin; RVDPVNFKLLSH) is the major peptide of a family of endogenous peptide endocannabinoids (pepcans) shown to act as negative allosteric modulators (NAM) of cannabinoid CB1 receptors. Noradrenergic neurons have been identified to be a specific site of pepcan production. However, it remains unknown whether pepcans occur in the periphery and interact with peripheral CB2 cannabinoid receptors. Here, it is shown that pepcan-12 acts as a potent (K
i
value ~50 nM) hCB2 receptor positive allosteric modulator (PAM). It significantly potentiated the effects of CB2 receptor agonists, including the endocannabinoid 2-arachidonoyl glycerol (2-AG), for [35S]GTPγS binding and cAMP inhibition (5–10 fold). In mice, the putative precursor pepcan-23 (SALSDLHAHKLRVDPVNFKLLSH) was identified with pepcan-12 in brain, liver and kidney. Pepcan-12 was increased upon endotoxemia and ischemia reperfusion damage where CB2 receptors play a protective role. The adrenals are a major endocrine site of production/secretion of constitutive pepcan-12, as shown by its marked loss after adrenalectomy. However, upon I/R damage pepcan-12 was strongly increased in the liver (from ~100 pmol/g to ~500 pmol/g) independent of adrenals. The wide occurrence of this endogenous hormone-like CB2 receptor PAM, with unforeseen opposite allosteric effects on cannabinoid receptors, suggests its potential role in peripheral pathophysiological processes.
Evidence-based tailoring of bioinformatics approaches to optimize methods that predict the effects of nonsynonymous amino acid substitutions in glucokinase
Authors: Šimčíková Daniela , Kocková Lucie , Vackářová Kateřina , Těšínský Miroslav , Heneberg Petr
Published: August 2017

Computational methods that allow predicting the effects of nonsynonymous substitutions are an integral part of exome studies. Here, we validated and improved their specificity by performing a comprehensive bioinformatics analysis combined with experimental and clinical data on a model of glucokinase (GCK): 8835 putative variations, including 515 disease-associated variations from 1596 families with diagnoses of monogenic diabetes (GCK-MODY) or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), and 126 variations with available or newly reported (19 variations) data on enzyme kinetics. We also proved that high frequency of disease-associated variations found in patients is closely related to their evolutionary conservation. The default set prediction methods predicted correctly the effects of only a part of theGCK-MODY-associated variations and completely failed to predict the normoglycemic or PHHI-associated variations. Therefore, we calculated evidence-based thresholds that improved significantly the specificity of predictions (≤75%). The combined prediction analysis even allowed to distinguish activating from inactivating variations and identified a group of putatively highly pathogenic variations (EVmutation score <−7.5 and SNAP2 score >70), which were surprisingly underrepresented among MODY patients and thus under negative selection during molecular evolution. We suggested and validated the first robust evidence-based thresholds, which allow improved, highly specific predictions of disease-associated GCK variations.
The validity and reliability of remote diabetic foot ulcer assessment using mobile phone images
Authors: van Netten Jaap J. , Clark Damien , Lazzarini Peter A. , Janda Monika , Reed Lloyd F.
Published: August 2017

Despite their potential for telemedicine in diabetic foot ulcer treatment, diagnostic accuracy of assessment of diabetic foot ulcers using mobile phone images is unknown. Our aim was to determine the validity and reliability of remote diabetic foot ulcer assessment using mobile phone images. Fifty diabetic foot ulcers were assessed live and photographed. Five independent observers remotely assessed the mobile phone images twice for presence of nine clinical characteristics and three treatment decisions. Positive likelihood (LLR+) and negative likelihood (LLR−) ratios were calculated for validity. Multirater Randolph’s and bi-rater Bennet kappa values were calculated for reliability. LLR+ ranged from 1.3–4.2; LLR− ranged from 0.13–0.88; the treatment decision ‘peri-wound debridement’ was the only item with ‘strong diagnostic evidence’. Inter-observer reliability kappa ranged from 0.09–0.71; test-retest reliability from 0.45–0.86; the treatment decision ‘peri-wound debridement’ was the only item with ‘adequate agreement’. In conclusion, mobile phone images had low validity and reliability for remote assessment of diabetic foot ulcers and should not be used as a stand-alone diagnostic instrument. Clinicians who use mobile phone images in clinical practice should obtain as much additional information as possible when making treatment decisions based on these images, and be cautious of the low diagnostic accuracy.
Prevalence and risk factors associated with stroke in middle-aged and older Chinese: A community-based cross-sectional study
Authors: Gan Yong , Wu Jiang , Zhang Shengchao , Li Liqing , Yin Xiaoxv , Gong Yanhong , Herath Chulani , Mkandawire Naomie , Zhou Yanfeng , Song Xingyue , Zeng Xiaozhou , Li Wenzhen , Liu Qiaoyan , Shu Chang , Wang Zhihong , Lu Zuxun
Published: August 2017

Although the prevalence of stroke and its risk factors has been widely reported in some Western countries, information on essential stroke parameters is lacking in China, the most populous nation. A community-based cross-sectional study with 8,018 Chinese adults aged ≥40 years was used to determine the prevalence of stroke and associated risk factors. Within the screened population, the prevalence of stroke was 2.21% for both sexes, 1.60% for females, and 3.18% for males. Prevalence increased with age in both sexes (P < 0.0001). In a multivariable model, factors significantly associated with stroke were increasing age (odds ratio [OR] = 1.87, 95% CI: 1.58–2.24), male gender (OR = 2.03, 95% CI: 1.42–2.90), family history of stroke (OR = 4.33, 95% CI: 2.89–6.49), history of hyperlipidemia (OR = 1.87, 95% CI 1.31–2.68), history of hypertension (OR = 1.47, 95% CI 1.02–2.12), and physical inactivity (OR = 1.74, 95% CI: 1.16–2.59). The findings indicate that stroke prevalence in middle-aged and older Chinese adults is higher in males than in females, and increases with age in both sexes. Population-based public health intervention programs and policies targeting hyperlipidemia and hypertension control and encouragement of physical activity should be highly prioritized for middle-aged and older adults in Shenzhen, China.
Spatial multi-scale relationships of ecosystem services: A case study using a geostatistical methodology
Authors: Liu Yang , Bi Jun , Lv Jianshu , Ma Zongwei , Wang Ce
Published: August 2017

Adequately understanding the spatial multi-scale relationships of ecosystem services (ES) is an important step for environmental management decision-making. Here, we used spatially explicit methods to estimate five critical ES (nitrogen and phosphorous purifications, crop production, water supply and soil retention) related to non-point source (NPS) pollution in the Taihu Basin region of eastern China. Then a factorial kriging analysis and stepwise multiple regression were performed to identify the spatial multi-scale relationships of ES and their dominant factors at each scale. The spatial variations in ES were characterized at the 12 km and 83 km scales and the result indicated that the relationships of these services were scale dependent. It was inferred that at the 12 km scale, ES were controlled by anthropogenic activities and their relationships were dependent on socio-economic factors. At the 83 km scale, we suggested that ES were primarily dominated by the physical environment. Moreover, the policy implications of ES relationships and their dominant factors were discussed for the multi-level governance of NPS pollution. Overall, this study presents an optimized approach to identifying ES relationships at multiple spatial scales and illustrates how appropriate information can help guide water management.
fNIRS can robustly measure brain activity during memory encoding and retrieval in healthy subjects
Authors: Jahani Sahar , Fantana Antoniu L. , Harper David , Ellison James M. , Boas David A. , Forester Brent P. , Yücel Meryem A.
Published: August 2017

Early intervention in Alzheimer’s Disease (AD) requires novel biomarkers that can capture changes in brain activity at an early stage. Current AD biomarkers are expensive and/or invasive and therefore unsuitable for use as screening tools, but a non-invasive, inexpensive, easily accessible screening method could be useful in both clinical and research settings. Prior studies suggest that especially paired-associate learning tasks may be useful in detecting the earliest memory impairment in AD. Here, we investigated the utility of functional Near Infrared Spectroscopy in measuring brain activity from prefrontal, parietal and temporal cortices of healthy adults (n = 19) during memory encoding and retrieval under a face-name paired-associate learning task. Our findings demonstrate that encoding of novel face-name pairs compared to baseline as well as compared to repeated face-name pairs resulted in significant activation in left dorsolateral prefrontal cortex while recalling resulted in activation in dorsolateral prefrontal cortex bilaterally. Moreover, brain response to recalling was significantly higher than encoding in medial, superior and middle frontal cortices for novel faces. Overall, this study shows that fNIRS can reliably measure cortical brain activation during a face-name paired-associate learning task. Future work will include similar measurements in populations with progressing memory deficits.
Nanoceria-mediated delivery of doxorubicin enhances the anti-tumour efficiency in ovarian cancer cells via apoptosis
Authors: Das Joydeep , Choi Yun-Jung , Han Jae Woong , Reza Abu Musa Md Talimur , Kim Jin-Hoi
Published: August 2017

Nanocarriers are widely used for effective delivery of anticancer drugs to tumours with potential to improve cancer treatment. Here, we developed a nanoceria (CeO2)-based system for delivery of the anti-cancer drug doxorubicin (DOX) to human ovarian cancer cells. Negatively charged nanoceria could conjugate with the cationic DOX via electrostatic interaction under physiological conditions, forming DOX-loaded nanoceria (CeO2/DOX). CeO2/DOX particles displayed nearly spherical shapes, along with superior drug-loading content (22.41%), loading efficiency (99.51%), and higher cellular uptake and drug release behaviours compared to free DOX. Moreover, DOX was released faster from CeO2/DOX under reductive acidic conditions (pH 5.0, 10 mM glutathione) than under physiological conditions (pH 7.4). The initial intracellular DOX concentration was higher in the free DOX groups than in the CeO2/DOX groups, but quickly reduced to 25% of the initial concentration after 24-h culture. By contrast, CeO2/DOX showed sustained DOX release over time and maintained a high intracellular DOX concentration for up to 72 h. In vitro assays showed that CeO2/DOX exhibited higher cell proliferation inhibition and apoptosis compared with free DOX. These results highlight DOX-loaded nanoceria as a promising therapeutic agent for cancer treatment.
Chemometric analysis of cow dung ash as an adsorbent for purifying biodiesel from waste cooking oil
Authors: Avinash A. , Murugesan A.
Published: August 2017

Taraditionally, the water-soluble contaminants of biodiesel are treated by water wash method. However, water wash method ends up in an aqueous effluent, which might then cause a harmful environmental impact. As a consequence, waterless purification of biodiesel has triggered primary interest in biodiesel manufacturing process. To address this issue, an endeavour has been made in this work to investigate the waterless purification of biodiesel from waste cooking oil using cow dung ash at different concentration of 1, 2, 3 and 4 wt/wt %. The optimum concentration of cow dung ash for biodiesel purification was found through chemometric analysis by comparing the Fourier transform infrared transmission (FTIR) spectral characteristics of cow dung ash with the water treated FTIR. It was observed from the experimental study that 1 wt/wt % of cow dung ash exhibited similar structural characteristics as that of traditional water treated method of biodiesel purification. Therefore, bio-waste cow dung ash is an effective adsorbent in purifying biodiesel analogous to traditional water washing technology.
Simultaneous emission of Gaussian-like and parabolic-like pulse waveforms in an erbium-doped dual-wavelength fiber laser
Authors: Li Xing , Dai Shenggan , Zou Weiwen , Chen Jianping , Nie Qiuhua , Dai Shixun
Published: August 2017

We report on the observation of different pulse formation dynamics in a nonlinear polarization evolution (NPE)-based broadband erbium-doped fiber laser when the net cavity group-velocity dispersion (GVD) is managed to be close to zero. The fiber laser can generate pulses with a single wavelength or dual wavelengths by adjusting the waveplates. When the laser operates in dual-wavelength emission, the output pulses corresponding to the two wavelengths exhibit Gaussian- and parabolic-like waveforms, respectively, indicating that the laser can simultaneously operate in stretched-pulse and self-similar regimes. The generation of dual-wavelength emission with different pulse waveforms can be attributed to an overdriven NPE switch acting on a chirped broadband pulse and different dispersion mechanisms. These findings provide a good foundation for comprehensively studying pulse formation dynamics in laser cavities.
Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields
Authors: Parate Dinesh , Franco-Obregón Alfredo , Fröhlich Jürg , Beyer Christian , Abbas Azlina A. , Kamarul Tunku , Hui James H. P. , Yang Zheng
Published: August 2017

Pulse electromagnetic fields (PEMFs) have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF parameters over mesenchymal stem cells (MSC) chondrogenic differentiation. MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, duration and frequency of exposure. Contrary to conventional practice of administering prolonged and repetitive exposures to PEMFs, optimal chondrogenic outcome is achieved in response to brief (10 minutes), low intensity (2 mT) exposure to 6 ms bursts of magnetic pulses, at 15 Hz, administered only once at the onset of chondrogenic induction. By contrast, repeated exposures diminished chondrogenic outcome and could be attributed to calcium entry after the initial induction. Transient receptor potential (TRP) channels appear to mediate these aspects of PEMF stimulation, serving as a conduit for extracellular calcium. Preventing calcium entry during the repeated PEMF exposure with the co-administration of EGTA or TRP channel antagonists precluded the inhibition of differentiation. This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF regimens has clear clinical implications for future regenerative strategies for cartilage.
Expression and role of VLA-1 in resident memory CD8 T cell responses to respiratory mucosal viral-vectored immunization against tuberculosis
Authors: Haddadi Siamak , Thanthrige-Don Niroshan , Afkhami Sam , Khera Amandeep , Jeyanathan Mangalakumari , Xing Zhou
Published: August 2017

Lung resident memory T cells (TRM) characterized by selective expression of mucosal integrins VLA-1 (α1β1) and CD103 (αEβ7) are generated following primary respiratory viral infections. Despite recent progress, the generation of lung TRM and the role of mucosal integrins following viral vector respiratory mucosal immunization still remains poorly understood. Here by using a replication-defective viral vector tuberculosis vaccine, we show that lung Ag-specific CD8 T cells express both VLA-1 and CD103 following respiratory mucosal immunization. However, VLA-1 and CD103 are acquired in differential tissue sites with the former acquired during T cell priming in the draining lymph nodes and the latter acquired after T cells entered the lung. Once in the lung, Ag-specific CD8 T cells continue to express VLA-1 at high levels through the effector/expansion, contraction, and memory phases of T cell responses. Using a functional VLA-1 blocking mAb, we show that VLA-1 is not required for trafficking of these cells to the lung, but it negatively regulates them in the contraction phase. Furthermore, VLA-1 plays a negligible role in the maintenance of these cells in the lung. Our study provides new information on vaccine-inducible lung TRM and shall help develop effective viral vector respiratory mucosal tuberculosis vaccination strategies.
A robust superhydrophobic TiO2 NPs coated cellulose sponge for highly efficient oil-water separation
Authors: Zhang Hui , Li Yuqi , Lu Zexiang , Chen Lihui , Huang Liulian , Fan Mizi
Published: August 2017

Oil-water separation has recently become a worldwide concern because of the increasing oil spill accidents and industrial oily wastewater generation. Herein, a facile method with the combined superhydrophobic coating and adhesive was used to fabricate superhydrophobic TiO2 NPs coated cellulose sponge. The developed materials exhibited excellent superhydrophobicity (WCA = 171°) and superoleophilicity (OCA = 0°), which can separate a variety of oil-water mixtures, including chloroform, toluene, kerosene and other contaminations. A high separation efficiency up to 98.5% for chloroform-water mixture was achieved when used for gravity-driven oil/water separation test. More importantly, the as-prepared samples exhibited excellent chemical stability and mechanical abrasion resistance even towards various corrosive oil/water mixtures (such as strong acid, alkali solution and salt-water environment) or a strong abrasion by aluminium oxide sandpaper of 600 mesh. In addition, the separation efficiency remained above 93% even after 40 scratch cycles, and the materials could be reused with a stable hydrophobicity, indicating a strong potential for industrial application.
Modeling acute toxicity of metal mixtures to wheat (Triticum aestivum L.) using the biotic ligand model-based toxic units method
Authors: Wu Mingyan , Wang Xuedong , Jia Zhiguo , De Schamphelaere Karel , Ji Dongxue , Li Xiaoxiu , Chen Xiaolin
Published: August 2017

The combined toxic effects of copper (Cu) and cobalt (Co) were predicted using the biotic ligand model (BLM) for different concentrations of magnesium (Mg2+) and pH levels, with parameters derived from Cu-only and Co-only toxicity data. The BLM-based toxic unit (TU) approach was used for prediction. Higher activities of Mg2+ linearly increased the EC50 of Cu and Co, supporting the concept of competitive binding of Mg2+ and metal ions in toxic action. The effects of pH on Cu and Co toxicity were related not only to free Cu2+ and Co2+ activity, respectively, but also to inorganic metal complexes. Stability constants for the binding of Cu2+, CuHCO3+, CuCO3(aq), CuOH+, Mg2+, Co2+, CoHCO3+ and Mg2+ with biotic ligands were logKCuBL 5.87, $$\mathrm{log}\,{K}_{{{\rm{CuHCO}}}_{3}{\rm{BL}}}$$
log

K

CuHCO

3

BL

5.67, $$\mathrm{log}\,{K}_{{{\rm{CuCO}}}_{3}{\rm{BL}}}$$
log

K

CuCO

3

BL

5.44, logKCuOHBL 5.07, logKMgBL 2.93, logKCoBL 4.72, $$\mathrm{log}\,{K}_{{{\rm{CoHCO}}}_{3}{\rm{BL}}}$$
log

K

CoHCO

3

BL

5.81 and logKMgBL 3.84, respectively. The combinations of Cu and Co showed additive effects under different conditions. When compared with the FIAM-based TU model (root mean square error [RMSE = 16.31, R2 = 0.84]), the BLM-based TU model fitted the observed effects better (RMSE = 6.70, R2 = 0.97). The present study supports the BLM principles, which indicate that metal speciation and major cations competition need to be accounted for when predicting toxicity of both single metals and mixtures of metals.
Effects of drying and wetting cycles on the transformations of extraneous inorganic N to soil microbial residues
Authors: Zhang Wei , Liang Chao , Kao-Kniffin Jenny , He Hongbo , Xie Hongtu , Zhang Xudong
Published: August 2017

The incorporation of extraneous nitrogen (N) into amino sugars (AS) could reflect the contribution of microbial residues to soil N transformation. Investigating the impact of drying-wetting (DW) on dynamics of newly-produced AS is critical because this represents microbial-driven N retention/losses in soil. A 36-day incubation of soil samples was conducted under different drying intensities, using 15N-labelled-(NH4)2SO4 as an N source together with/without glucose addition. There were multiple DW periods and they ranged from a constant moisture content treatment, to a one day drying (low-drying-intensity, LD), a two day drying (medium-drying-intensity, MD), or a three day drying event (severe-drying-intensity, SD). The immobilization of added-N was restricted in DW when available carbon was not added, thus glucose addition increased the effect of DW on the incorporation of added-N into AS. The response of total 15N-AS to DW varied depending on drying intensities. The MD was beneficial to the incorporation of added-N into total 15N-AS, while total 15N-AS contents were low in SD treatment. The effect of DW on contribution of bacterial and fungal residues to N transformation was also related to drying intensities. Our study indicated that DW altered microbial transformation of added-N, and the effect was drying intensity-specific, and available carbon-dependent.
EnSVMB: Metagenomics Fragments Classification using Ensemble SVM and BLAST
Authors: Jiang Yuan , Wang Jun , Xia Dawen , Yu Guoxian
Published: August 2017

Metagenomics brings in new discoveries and insights into the uncultured microbial world. One fundamental task in metagenomics analysis is to determine the taxonomy of raw sequence fragments. Modern sequencing technologies produce relatively short fragments and greatly increase the number of fragments, and thus make the taxonomic classification considerably more difficult than before. Therefore, fast and accurate techniques are called to classify large-scale fragments. We propose EnSVM (Ensemble Support Vector Machine) and its advanced method called EnSVMB (EnSVM with BLAST) to accurately classify fragments. EnSVM divides fragments into a large confident (or small diffident) set, based on whether the fragments get consistent (or inconsistent) predictions from linear SVMs trained with different k-mers. Empirical study shows that sensitivity and specificity of EnSVM on confident set are higher than 90% and 97%, but on diffident set are lower than 60% and 75%. To further improve the performance on diffident set, EnSVMB takes advantage of best hits of BLAST to reclassify fragments in that set. Experimental results show EnSVM can efficiently and effectively divide fragments into confident and diffident sets, and EnSVMB achieves higher accuracy, sensitivity and more true positives than related state-of-the-art methods and holds comparable specificity with the best of them.
Population mechanics: A mathematical framework to study T cell homeostasis
Authors: Arias Clemente F. , Herrero Miguel A. , Acosta Francisco J. , Fernandez-Arias Cristina
Published: August 2017

Unlike other cell types, T cells do not form spatially arranged tissues, but move independently throughout the body. Accordingly, the number of T cells in the organism does not depend on physical constraints imposed by the shape or size of specific organs. Instead, it is determined by competition for interleukins. From the perspective of classical population dynamics, competition for resources seems to be at odds with the observed high clone diversity, leading to the so-called diversity paradox. In this work we make use of population mechanics, a non-standard theoretical approach to T cell homeostasis that accounts for clone diversity as arising from competition for interleukins. The proposed models show that carrying capacities of T cell populations naturally emerge from the balance between interleukins production and consumption. These models also suggest remarkable functional differences in the maintenance of diversity in naïve and memory pools. In particular, the distribution of memory clones would be biased towards clones activated more recently, or responding to more aggressive pathogenic threats. In contrast, permanence of naïve T cell clones would be determined by their affinity for cognate antigens. From this viewpoint, positive and negative selection can be understood as mechanisms to maximize naïve T cell diversity.
Fe-based hybrid electrocatalysts for nonaqueous lithium-oxygen batteries
Authors: Lee Seun , Lee Gwang-Hee , Lee Hack Jun , Dar Mushtaq Ahmad , Kim Dong-Wan
Published: August 2017

Lithium–oxygen batteries promise high energy densities, but are confronted with challenges, such as high overpotentials and sudden death during discharge–charge cycling, because the oxygen electrode is covered with the insulating discharge product, Li2O2. Here, we synthesized low–cost Fe–based nanocomposites via an electrical wire pulse process, as a hybrid electrocatalyst for the oxygen electrode of Li–O2batteries. Fe3O4-Fe nanohybrids–containing electrodes exhibited a high discharge capacity (13,890 mA h gc−1at a current density of 500 mA gc−1), long cycle stability (100 cycles at a current rate of 500 mA gc−1and fixed capacity regime of 1,000 mA h gc−1), and low overpotential (1.39 V at 40 cycles). This superior performance resulted from the good electrical conductivity of the Fe metal nanoparticles during discharge–charge cycling, which could enhance the oxygen reduction reaction and oxygen evolution reaction activities. We have demonstrated the increased electrical conductivity of the Fe3O4-Fe nanohybrids using electrochemical impedance spectroscopy.
Efficacy of Laropiprant in Minimizing Brain Injury Following Experimental Intracerebral Hemorrhage
Authors: Ahmad Abdullah Shafique , Mendes Monique , Hernandez Damian , Doré Sylvain
Published: August 2017

Intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke, yet effective treatments are still lacking. Prostaglandins and their receptors have been implicated in playing vital roles in ICH outcomes. Recently, laropiprant, a DP1 receptor antagonist, has been used in combination with niacin to abolish the prostaglandin D2-(PGD2)-induced flushing. Here, we test the hypothesis that laropiprant limits bleeding and rescues the brain from ICH. Wildtype (WT) and DP1−/− mice were subjected ICH and neurologic deficits and hemorrhagic lesion outcomes were evaluated at 72 hours after the ICH. To test the therapeutic potential of laropiprant, WT mice subjected to ICH were treated with laropiprant at 1 hour after the ICH. The putative effect of laropiprant on limiting hematoma expansion was tested by an in vivo tail bleeding cessation method and an ex vivo coagulation method. Finally, the roles of laropiprant on gliosis and iron accumulation were also investigated. A significant decrease in the injury volume was observed in DP1−/− as well as laropiprant-treated WT mice. The tail bleeding time was significantly lower in laropiprant group as compared with the vehicle group. Significantly lower Iba-1 and Perls’ iron staining in DP1−/− and laropiprant-treated WT groups were observed. Altogether, the data suggest that laropiprant treatment post-ICH attenuates brain damage by targeting primary as well as secondary injuries.
Biochips for Direct Detection and Identification of Bacteria in Blood Culture-Like Conditions
Authors: Templier V. , Livache T. , Boisset S. , Maurin M. , Slimani S. , Mathey R. , Roupioz Y.
Published: August 2017

Bloodstream bacterial infections are life-threatening conditions necessitating prompt medical care. Rapid pathogen identification is essential for early setting of the best anti-infectious therapy. However, the bacterial load in blood samples from patients with bacteremia is too low and under the limit of detection of most methods for direct identification of bacteria. Therefore, a preliminary step enabling the bacterial multiplication is required. To do so, blood cultures still remain the gold standard before bacteremia diagnosis. Bacterial identification is then usually obtained within 24 to 48 hours -at least- after blood sampling. In the present work, the fast and direct identification of bacteria present in blood cultures is completed in less than 12 hours, during bacterial growth, using an antibody microarray coupled to a Surface Plasmon Resonance imager (SPRi). Less than one bacterium (Salmonella enterica serovar Enteritidis) per milliliter of blood sample is successfully detected and identified in blood volumes similar to blood tests collected in clinics (i.e. several milliliters). This proof of concept demonstrates the workability of our method for human samples, despite the highly complex intrinsic nature of unprocessed blood. Our label-free method then opens new perspectives for direct and faster bacterial identification in a larger range of clinical samples.
FISH-based mitotic and meiotic diakinesis karyotypes of Morus notabilis reveal a chromosomal fusion-fission cycle between mitotic and meiotic phases
Authors: Xuan Yahui , Li Chaoshuo , Wu Yue , Ma Bi , Liu Ruiling , Xiang Zhonghuai , He Ningjia
Published: August 2017

Mulberry (Morus spp.), in family Moraceae, is a plant with important economic value. Many polyploid levels of mulberry have been determined. In the present study, the fluorescence in situ hybridization (FISH) technique was applied in Morus notabilis, using four single-copy sequences, telomere repeats, and 5S and 25S rDNAs as probes. All the mitotic chromosomes were clearly identified and grouped into seven pairs of homologous chromosomes. Three dot chromosome pairs were distinguished by the FISH patterns of the 25S rDNA probe and a simple sequence repeat (SSR2524). According to the FISH signals, chromosome length and morphology, detailed meiotic diakinesis karyotype was constructed. Interestingly, only six bivalent chromosomes were observed in diakinesis cells. The 25S rDNA probe was used to illustrate chromosome alterations. The results indicated that mitotic chromosomes 5 and 7 fused into diakinesis chromosome 5 during the meiotic phase. In mitotic cells, the fused chromosome 5 broke into chromosomes 5 and 7. A chromosomal fusion-fission cycle between the meiotic and mitotic phases in the same individual is reported here for the first time. This finding will contribute to the understanding of karyotype evolution in plants.
Low Tube Voltage Liver MDCT with Sinogram-Affirmed Iterative Reconstructions for the Detection of Hepatocellular Carcinoma
Authors: Pregler B. , Beyer L. P. , Teufel A. , Niessen C. , Stroszczynski C. , Brodoefel H. , Wiggermann P.
Published: August 2017

Aim of this study was to compare low tube voltage computed tomography (80 kV) of the liver using iterative image reconstruction (SAFIRE) with standard computed tomography (120 kV) using filtered back-projection (FBP) for the detection of hepatocellular carcinoma (HCC). 46 patients (43 men) with 93 HCC confirmed by 3 T MRI with Gd-EOB-DPTA, in inconclusive cases combined with contrast-enhanced ultrasound, underwent dual-energy CT. The raw data of the 80 kV tube was reconstructed using the iterative reconstruction algorithm SAFIRE with two strengths (I3 and I5). The virtual 120 kV image data set was reconstructed using FBP. The CT images were reviewed to determine the lesion-to-liver contrast (LLC), the lesion contrast-to-noise ratio (CNR) and the sensitivity. The LLC (57.1/54.3 [I3/I5] vs. 34.9 [FBP]; p ≤ 0.01), CNR (3.67/4.45 [I3/I5] vs. 2.48 [FBP]; p < 0.01) and sensitivity (91.4%/88.2% [I3/I5] vs. 72.0% [FBP]; p ≤ 0.01) were significantly higher in the low-voltage protocol using SAFIRE. Therefore, low tube voltage CT using SAFIRE results in an increased lesion-to-liver contrast as well as an improved lesion contrast-to-noise ratio compared to FBP at 120 kV which results in a higher sensitivity for the detection of HCC.
The cellular and molecular determinants of emphysematous destruction in COPD
Authors: Suzuki Masaru , Sze Marc A. , Campbell Joshua D. , Brothers John F. , Lenburg Marc E. , McDonough John E. , Elliott W. Mark , Cooper Joel D. , Spira Avrum , Hogg James C.
Published: August 2017

The introduction of microCT has made it possible to show that the terminal bronchioles are narrowed and destroyed before the onset of emphysematous destruction in COPD. This report extends those observations to the cellular and molecular level in the centrilobular phenotype of emphysematous destruction in lungs donated by persons with very severe COPD (n = 4) treated by lung transplantation with unused donor lungs (n = 4) serving as controls. These lung specimens provided companion samples to those previously examined by microCT (n = 61) that we examined using quantitative histology (n = 61) and gene expression profiling (n = 48). The histological analysis showed that remodeling and destruction of the bronchiolar and alveolar tissue is associated with macrophage, CD4, CD8, and B cell infiltration with increased formation of tertiary lymphoid organs. Moreover, gene set enrichment analysis showed that genes known to be expressed by natural killer (NK), lymphoid tissue inducer (LTi), and innate lymphoid cell 1 (ILC1) cells, but not ILC2 or ILC3 cells, were enriched in the expression profiles associated with CD4, CD8, and B cell infiltration. Based on these findings, we postulate that the centrilobular phenotype of emphysematous destruction COPD is driven by a Th1 response activated by infiltrating ILC1, NK, and LTi cells.
The Impact of the Polymer Chain Length on the Catalytic Activity of Poly(N-vinyl-2-pyrrolidone)-supported Gold Nanoclusters
Authors: Haesuwannakij Setsiri , Kimura Tetsunari , Furutani Yuji , Okumura Kazu , Kokubo Ken , Sakata Takao , Yasuda Hidehiro , Yakiyama Yumi , Sakurai Hidehiro
Published: August 2017

Poly(N-vinyl-2-pyrrolidone) (PVP) of varying molecular weight (M
w
 = 40-360 kDa) were employed to stabilize gold nanoclusters of varying size. The resulting Au:PVP clusters were subsequently used as catalysts for a kinetic study on the sized-dependent aerobic oxidation of 1-indanol, which was monitored by time-resolved in situ infrared spectroscopy. The obtained results suggest that the catalytic behaviour is intimately correlated to the size of the clusters, which in turn depends on the molecular weight of the PVPs. The highest catalytic activity was observed for clusters with a core size of ~7 nm, and the size of the cluster should increase with the molecular weight of the polymer in order to maintain optimal catalytic activity. Studies on the electronic and colloid structure of these clusters revealed that the negative charge density on the cluster surface also strongly depends on the molecular weight of the stabilizing polymers.
In vitro blood cell viability profiling of polymers used in molecular assembly
Authors: Jeong Hyejoong , Hwang Jangsun , Lee Hwankyu , Hammond Paula T. , Choi Jonghoon , Hong Jinkee
Published: August 2017

Biocompatible polymers have been extensively applied to molecular assembly techniques on a micro- and nanoscale to miniaturize functional devices for biomedical uses. However, cytotoxic assessments of developed devices are prone to partially focus on non-specific cells or cells associated with the specific applications. Thereby, since toxicity is dependent on the type of cells and protocols, we do not fully understand the relative toxicities of polymers. Additionally, we need to ensure the blood cell biocompatibility of developed devices prior to that of targeted cells because most of the devices contact the blood before reaching the targeted regions. Motivated by this issue, we focused on screening cytotoxicity of polymers widely used for the layer-by-layer assembly technique using human blood cells. Cytotoxicity at the early stage was investigated on twenty types of polymers (positively charged, negatively charged, or neutral) and ten combination forms via hemolysis, cell viability, and AnnexinV-FITC/PI staining assays. We determined their effects on the cell membrane depending on their surface chemistry by molecular dynamics simulations. Furthermore, the toxicity of LbL-assembled nanofilms was assessed by measuring cell viability. Based on this report, researchers can produce nanofilms that are better suited for drug delivery and biomedical applications by reducing the possible cytotoxicity.
HIV-1 envelope glycoprotein stimulates viral transcription and increases the infectivity of the progeny virus through the manipulation of cellular machinery
Authors: Ran Xiaozhuo , Ao Zhujun , Trajtman Adriana , Xu Wayne , Kobinger Gary , Keynan Yoav , Yao Xiaojian
Published: August 2017

During HIV infection, large amounts of progeny viral particles, including infectious virus and a large proportion of defective viral particles, are produced. Despite of the critical role of the infectious viruses in infection and pathogenesisin vivo, whether and how those defective viral particles, especially the virus-associated envelope glycoprotein (vEnv), would impact viral infection remains elusive. In this study, we investigated the effect of vEnv on HIV-infected T cells and demonstrated that the vEnv was able to stimulate HIV transcription in HIV-infected cells, including peripheral blood mononuclear cells (PBMCs) isolated from HIV patients. This vEnv-mediated HIV transcription activation is mediated primarily through the interaction between vEnv and CD4/coreceptors (CCR5 or CXCR4). Through transcriptome analysis, we found that numerous cellular gene products involved in various signaling pathways were modulated by vEnv. Among them, we have further identified a cellular microRNA miR181A2, which is downregulated upon vEnv treatment, resulting in increased HIV LTR histone H3 acetylation and HIV transcription. Furthermore, we also found a vEnv-modulated cellular histone deacetylase, HDAC10, whose downregulation is associated with the increased infectivity of progeny viruses. Altogether, these findings provide evidence of the important role vEnv plays in modulating cellular environments and facilitating HIV expression and infection.
Downregulation of PARP1 transcription by promoter-associated E2F4-RBL2-HDAC1-BRM complex contributes to repression of pluripotency stem cell factors in human monocytes
Authors: Wiśnik Ewelina , Płoszaj Tomasz , Robaszkiewicz Agnieszka
Published: August 2017

Differentiation of certain cell types is followed by a downregulation of PARP1 expression. We show that the reduction in the abundance of PARP1 in hematopoietic progenitor cells and monocytes is tightly controlled by the cell cycle. The differentiation-associated cell cycle exit induces E2F1 replacement with E2F4 at the PARP1 promoter and the assembly of an E2F4-RBL2-HDAC1-BRM(SWI/SNF) repressor complex which deacetylates nucleosomes and compacts chromatin. In G1 arrested cells, PARP1 transcription is reduced by the recruitment of E2F1-RB1-HDAC1-EZH2(PRC2)-BRM/BRG1(SWI/SNF), which additionally trimethylates H3K27 and causes an even higher increase in nucleosome density. The re-establishment of an active chromatin structure by treating post-mitotic monocytes with the HDAC inhibitor and G1 arrested cells with a combination of HDAC and EZH2 inhibitors restores PARP1 expression completely but does not affect the interaction between the components of the repressor complex with chromatin. This suggests that RB1 and RBL2, as well as PRC2, SWI/SNF and HDAC1, do not interfere with the transcription machinery. Interestingly, reinstatement of PARP1 expression by the silencing of RBL2 or by the inhibition of HDACs in monocytes and by transfection with the PARP1 expression vector in differentiated THP-1 cells substantially increased transcription of pluripotency stem cell factors such as POU5F1, SOX2 and NANOG.
Efficacy and safety of different doses of cytarabine in consolidation therapy for adult acute myeloid leukemia patients: a network meta-analysis
Authors: Wu Di , Duan Chongyang , Chen Liyong , Chen Size
Published: August 2017

Cytarabine (Ara-C) in consolidation therapy played important role in preventing relapses for AML patients achieved complete remission, but the optimum dose remains elusive. In this network meta-analysis, we compared benefit and safety of high-, intermediate- and low-dose Ara-C [HDAraC (>2 g/m2, ≤3 g/m2 twice daily), IDAraC (≥1 g/m2, ≤2 g/m2 twice daily) and LDAraC (<1 g/m2 twice day)] in consolidation, based on ten randomized phase III/IV trials from 1994 to 2016, which included 4008 adult AML patients. According to the results, HDAraC in a dosage of 3 g/m2 twice daily significantly improved disease-free survival (DFS) compared with IDAraC [hazard rate (HR) 0.87, 95% CrI 0.79–0.97) and LDAraC (HR 0.86, 95% CrI 0.78–0.95). Subgroup analysis further showed that the DFS advantage of HDAraC is focused on the patients with favorable cytogenetics, but not the other cytogenetics. Compared with LDAraC, HDAraC (HR 6.04, 95% CrI 1.67–21.49) and IDAraC (HR 3.80, 95% CrI 1.05–12.85) were associated with higher risk of grade 3–4 non-haematological toxicity. However, no significant difference between HDAraC and IDAraC was found. These findings suggest that Ara-C in a dosage of 3 g/m2 twice daily provides maximal anti-relapse effect.