bluuebunny/crossref_metadata_2025 huggingface dataset:
Photosensitizer in lipid nanoparticle: a nano-scaled approach to antibacterial function
Authors: Rout Bishakh , Liu Chi-Hsien , Wu Wei-Chi
Published: August 2017

Photosensitization-based antimicrobial therapy (PAT) is an alternative therapy aimed at achieving bacterial inactivation. Researchers use various photosensitizers to achieve bacterial inactivation. However, the most widely used approach involves the use of photosensitizers dispersed in aqueous solution, which could limit the effectiveness of photodynamic inactivation. Therefore, the approaches to encapsulate the photosensitizer in appropriate vehicles can enhance the delivery of the photosensitizer. Herein, Toluidine Blue O (TBO) was the photosensitizer, and lipid nanoparticles were used for its encapsulation. The lipid nanoparticle-based delivery system has been tailor-made for decreasing the average size and viscosity and increasing the formulation stability as well as the wettability of skin. Usage of an appropriate vehicle will also increase the cellular uptake of the photosensitizer into the bacterial cells, leading to the damage on cell membrane and genomic DNA. Evidence of effectiveness of the developed PAT on planktonic bacteria and biofilms was examined by fluorescence microscopy and scanning electron microscopy. Lipid nanoparticles protected the photosensitizer from aggregation and made the application easy on the skin as indicated in data of size distribution and contact angle. The use of lipid nanoparticles for encapsulating TBO could enhance photosensitization-based antimicrobial therapy as compared to the aqueous media for delivering photosensitizers.
Decoupling Frequencies, Amplitudes and Phases in Nonlinear Optics
Authors: Schmidt Bruno E. , Lassonde Philippe , Ernotte Guilmot , Clerici Matteo , Morandotti Roberto , Ibrahim Heide , Légaré François
Published: August 2017

In linear optics, light fields do not mutually interact in a medium. However, they do mix when their field strength becomes comparable to electron binding energies in the so-called nonlinear optical regime. Such high fields are typically achieved with ultra-short laser pulses containing very broad frequency spectra where their amplitudes and phases are mutually coupled in a convolution process. Here, we describe a regime of nonlinear interactions without mixing of different frequencies. We demonstrate both in theory and experiment how frequency domain nonlinear optics overcomes the shortcomings arising from the convolution in conventional time domain interactions. We generate light fields with previously inaccessible properties by avoiding these uncontrolled couplings. Consequently, arbitrary phase functions are transferred linearly to other frequencies while preserving the general shape of the input spectrum. As a powerful application, we introduce deep UV phase control at 207 nm by using a conventional NIR pulse shaper.
The buckling instability of aggregating red blood cells
Authors: Flormann Daniel , Aouane Othmane , Kaestner Lars , Ruloff Christian , Misbah Chaouqi , Podgorski Thomas , Wagner Christian
Published: August 2017

Plasma proteins such as fibrinogen induce the aggregation of red blood cells (RBC) into rouleaux, which are responsible for the pronounced shear thinning behavior of blood, control the erythrocyte sedimentation rate (ESR) – a common hematological test – and are involved in many situations of physiological relevance such as structuration of blood in the microcirculation or clot formation in pathological situations. Confocal microscopy is used to characterize the shape of RBCs within rouleaux at equilibrium as a function of macromolecular concentration, revealing the diversity of contact zone morphology. Three different configurations that have only been partly predicted before are identified, namely parachute, male-female and sigmoid shapes, and quantitatively recovered by numerical simulations. A detailed experimental and theoretical analysis of clusters of two cells shows that the deformation increases nonlinearly with the interaction energy. Models indicate a forward bifurcation in which the contacting membrane undergoes a buckling instability from a flat to a deformed contact zone at a critical value of the interaction energy. These results are not only relevant for the understanding of the morphology and stability of RBC aggregates, but also for a whole class of interacting soft deformable objects such as vesicles, capsules or cells in tissues.
Virtual cardiac monolayers for electrical wave propagation
Authors: Kudryashova Nina , Tsvelaya Valeriya , Agladze Konstantin , Panfilov Alexander
Published: August 2017

The complex structure of cardiac tissue is considered to be one of the main determinants of an arrhythmogenic substrate. This study is aimed at developing the first mathematical model to describe the formation of cardiac tissue, using a joint in silico–in vitro approach. First, we performed experiments under various conditions to carefully characterise the morphology of cardiac tissue in a culture of neonatal rat ventricular cells. We considered two cell types, namely, cardiomyocytes and fibroblasts. Next, we proposed a mathematical model, based on the Glazier-Graner-Hogeweg model, which is widely used in tissue growth studies. The resultant tissue morphology was coupled to the detailed electrophysiological Korhonen-Majumder model for neonatal rat ventricular cardiomyocytes, in order to study wave propagation. The simulated waves had the same anisotropy ratio and wavefront complexity as those in the experiment. Thus, we conclude that our approach allows us to reproduce the morphological and physiological properties of cardiac tissue.
Identifying the tilt angle and correcting the orbital angular momentum spectrum dispersion of misaligned light beam
Authors: Zhao Peng , Li Shikang , Wang Yu , Feng Xue , Kaiyu Cui , Fang Liu , Zhang Wei , Huang Yidong
Published: August 2017

The axis tilt of light beam in optical system would introduce the dispersion of orbital angular momentum (OAM) spectrum. To deal with it, a two-step method is proposed and demonstrated. First, the tilt angle of optical axis is identified with a deduced relation between the tilt angle and the variation of OAM topological charges with different reference axes, which is obtained with the help of a charge coupled device (CCD) camera. In our experiments, the precision of measured tilt angle is about 10−4rad with topological charges of −3~3. With the measured angle value, the additional phase delay due to axis tilt can be calculated so that the dispersion of OAM spectrum can be corrected with a simple formula while the optical axis is not aligned. The experimental results indicate that the original OAM spectrum has been successfully extracted for not only the pure state but also the superposed OAM states.
Palladium nanoparticles entrapped in a self-supporting nanoporous gold wire as sensitive dopamine biosensor
Authors: Yi Xin , Wu Yuxuan , Tan Guoxin , Yu Peng , Zhou Lei , Zhou Zhengnan , Chen Junqi , Wang Zhengao , Pang Jinshan , Ning Chengyun
Published: August 2017

Traced dopamine (DA) detection is critical for the early diagnosis and prevention of some diseases such as Parkinson’s, Alzheimer and schizophrenia. In this research, a novel self-supporting three dimensional (3D) bicontinuous nanoporous electrochemical biosensor was developed for the detection of dopamine by Differential Pulse Voltammetry (DPV). This biosensor was fabricated by electrodepositing palladium nanoparticles (Pd) onto self-supporting nanoporous gold (NPG) wire. Because of the synergistic effects of the excellent catalytic activity of Pd and novel structure of NPG wire, the palladium nanoparticles decorated NPG (Pd/NPG) biosensor possess tremendous superiority in the detection of DA. The Pd/NPG wire biosensor exhibited high sensitivity of 1.19 μA μΜ−1, broad detection range of 1–220 μM and low detection limit up to 1 μM. Besides, the proposed dopamine biosensor possessed good stability, reproducibility, reusability and selectivity. The response currents of detection in the fetal bovine serum were also close to the standard solutions. Therefore the Pd/NPG wire biosensor is promising to been used in clinic.
Explosive death induced by mean–field diffusion in identical oscillators
Authors: Verma Umesh Kumar , Sharma Amit , Kamal Neeraj Kumar , Kurths Jürgen , Shrimali Manish Dev
Published: August 2017

We report the occurrence of an explosive death transition for the first time in an ensemble of identical limit cycle and chaotic oscillators coupled via mean–field diffusion. In both systems, the variation of the normalized amplitude with the coupling strength exhibits an abrupt and irreversible transition to death state from an oscillatory state and this first order phase transition to death state is independent of the size of the system. This transition is quite general and has been found in all the coupled systems where in–phase oscillations co–exist with a coupling dependent homogeneous steady state. The backward transition point for this phase transition has been calculated using linear stability analysis which is in complete agreement with the numerics.
Intestinal transepithelial permeability of oxytocin into the blood is dependent on the receptor for advanced glycation end products in mice
Authors: Higashida Haruhiro , Furuhara Kazumi , Yamauchi Agnes-Mikiko , Deguchi Kisaburo , Harashima Ai , Munesue Seiichi , Lopatina Olga , Gerasimenko Maria , Salmina Alla B. , Zhang Jia-Sheng , Kodama Hikari , Kuroda Hironori , Tsuji Chiharu , Suto Satoshi , Yamamoto Hiroshi , Yamamoto Yasuhiko
Published: August 2017

Plasma oxytocin (OT) originates from secretion from the pituitary gland into the circulation and from absorption of OT in mother’s milk into the blood via intestinal permeability. However, the molecular mechanism underlying the absorption of OT remains unclear. Here, we report that plasma OT concentrations increased within 10 min after oral delivery in postnatal day 1–7 mice. However, in Receptors for Advanced Glycation End Products (RAGE) knockout mice after postnatal day 3, an identical OT increase was not observed. In adult mice, plasma OT was also increased in a RAGE-dependent manner after oral delivery or direct administration into the intestinal tract. Mass spectrometry evaluated that OT was absorbed intact. RAGE was abundant in the intestinal epithelial cells in both suckling pups and adults. These data highlight that OT is transmitted via a receptor-mediated process with RAGE and suggest that oral OT supplementation may be advantageous in OT drug development.
Relationship between long working hours and periodontitis among the Korean workers
Authors: Lee Wanhyung , Lim Sung-Shil , Kim Byurira , Won Jong-Uk , Roh Jaehoon , Yoon Jin-Ha
Published: August 2017

We aimed to investigate the association between long working hours and periodontitis, and whether such an association constitutes an exposure-response relationship. Data for this study were collected from the Korea National Health and Nutrition Examination Surveys conducted from 2007 to 2014; 17,533 workers (9,483 of men and 8,050 of women) were included. The odds ratios (OR) and 95% confidence intervals (CI) for the analysis of periodontitis defined as positive of Community Periodontal Index in relation to working hours were calculated using multiple logistic regression models with various stratifications. Compared to participants who worked ≤40 hours per week, the prevalence ratio (95% CI) for the periodontitis was 1.19 (1.14–1.24) and full adjusted OR (95% CI) was 1.09 (1.02–1.18) in participants who worked over 40 hours per week. The OR (95% CI) for periodontitis were 1.09 (0.99–1.19) in working group of 40< and ≥52 and 1.10 (1.01–1.20) in working group of >52 hours per week with a significant trend (p = 0.0233) even after adjusting for age, socioeconomic status, healthy behaviour, chronic disease, and dental care status. Long working hours are associated with periodontitis among Korean workers in an exposure-response manner.
Targeting P-glycoprotein: Investigation of piperine analogs for overcoming drug resistance in cancer
Authors: Syed Safiulla Basha , Arya Hemant , Fu I-Hsuan , Yeh Teng-Kuang , Periyasamy Latha , Hsieh Hsing-Pang , Coumar Mohane Selvaraj
Published: August 2017

P-glycoprotein (P-gp) is a drug transporter that effluxes chemotherapeutic drugs and is implicated in the development of resistance of cancer cells to chemotherapeutic drugs. To date, no drug has been approved to inhibit P-gp and restore chemotherapy efficacy. Moreover, majority of the reported inhibitors have high molecular weight and complex structures, making it difficult to understand the basic structural requirement for P-gp inhibition. In this study, two structurally simple, low molecular weight piperine analogs Pip1 and Pip2 were designed and found to better interact with P-gp than piperinein silico. A one step, acid-amine coupling reaction between piperic acid and 6,7-dimethoxytetrahydroisoquinoline or 2-(3,4-dimethoxyphenyl)ethylamine afforded Pip1 and Pip2, respectively.In vitrotesting in drug resistant P-gp overexpressing KB (cervical) and SW480 (colon) cancer cells showed that both analogs, when co-administered with vincristine, colchicine or paclitaxel were able to reverse the resistance. Moreover, accumulation of P-gp substrate (rhodamine 123) in the resistant cells, a result of alteration of the P-gp efflux, was also observed. These investigations suggest that the natural product analog – Pip1 ((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1 H)-yl)penta-2,4-dien-1-one) – is superior to piperine and could inhibit P-gp function. Further studies are required to explore the full potential of Pip1 in treating drug resistant cancer.
The role of Snell’s law for a magnonic majority gate
Authors: Kanazawa Naoki , Goto Taichi , Sekiguchi Koji , Granovsky Alexander B. , Ross Caroline A. , Takagi Hiroyuki , Nakamura Yuichi , Uchida Hironaga , Inoue Mitsuteru
Published: August 2017

In the fifty years since the postulation of Moore’s Law, the increasing energy consumption in silicon electronics has motivated research into emerging devices. An attractive research direction is processing information via the phase of spin waves within magnonic-logic circuits, which function without charge transport and the accompanying heat generation. The functional completeness of magnonic logic circuits based on the majority function was recently proved. However, the performance of such logic circuits was rather poor due to the difficulty of controlling spin waves in the input junction of the waveguides. Here, we show how Snell’s law describes the propagation of spin waves in the junction of a Ψ-shaped magnonic majority gate composed of yttrium iron garnet with a partially metallized surface. Based on the analysis, we propose a magnonic counterpart of a core-cladding waveguide to control the wave propagation in the junction. This study has therefore experimentally demonstrated a fundamental building block of a magnonic logic circuit.
Comprehensive miRNA expression profiling in human T-cell acute lymphoblastic leukemia by small RNA-sequencing
Authors: Wallaert Annelynn , Van Loocke Wouter , Hernandez Lucie , Taghon Tom , Speleman Frank , Van Vlierberghe Pieter
Published: August 2017

T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background. Furthermore, small RNA-sequencing also unraveled the variety of isoforms that are expressed for each miRNA in T-ALL and showed that a significant number of miRNAs are actually represented by an alternative isomiR. Finally, comparison of CD34+ and CD4+CD8+ healthy donor thymocytes and T-ALL miRNA profiles allowed identifying several novel miRNAs with putative oncogenic or tumor suppressor functions in T-ALL. Altogether, this study provides a comprehensive overview of miRNA expression in normal and malignant T-cells and sets the stage for functional evaluation of novel miRNAs in T-ALL disease biology.
Relationship between higher-order wavefront aberrations and natural progression of myopia in schoolchildren
Authors: Hiraoka Takahiro , Kotsuka Junko , Kakita Tetsuhiko , Okamoto Fumiki , Oshika Tetsuro
Published: August 2017

This study investigated the relationship between higher-order aberrations (HOAs) and myopia progression as well as axial elongation in schoolchildren. We examined cycloplegic refraction, axial length, and wavefront aberrations prospectively in 71 myopic children. Changes in cycloplegic refraction and axial length during a 2-year study period were assessed, and their correlations with HOA components were analyzed. Sixty-four subjects ([mean ± SD] 9.2 ± 1.6 years) completed the 2-year examinations. Cycloplegic refraction was significantly changed after 2 years (P < 0.0001), and the average change (myopia progression) was −1.60 ± 1.04 D. Axial length also increased significantly (P < 0.0001), and the average increase (axial elongation) was 0.77 ± 0.40 mm. Myopia progression and axial elongation showed significant correlations with many components of corneal HOA (P < 0.0001 to P = 0.0270). Multivariate analysis showed that the total HOA of the cornea was the most relevant variable to myopia progression and axial elongation (P < 0.0001). Eyes with larger amounts of corneal HOAs showed less myopia progression and smaller axial elongation, suggesting that corneal HOAs play a role in the refractive and ocular developments in children.
Dual gene expression cassette is superior than single gene cassette for enhancing sheath blight tolerance in transgenic rice
Authors: Karmakar Subhasis , Molla Kutubuddin A. , Das Kaushik , Sarkar Sailendra Nath , Datta Swapan K. , Datta Karabi
Published: August 2017

Sheath blight, caused by the necrotrophic fungal pathogen Rhizoctonia solani, is a serious and destructive disease of the rice. In order to improve sheath blight resistance, we developed three different kinds of transgenic rice lines. The first transgenic line overexpresses the rice chitinase gene (OsCHI11); the second contains the Arabidopsis NPR1 (AtNPR1) gene and, the third has pyramided constructs with both the genes (OsCHI11 and AtNPR1). This is a comparative study between the single-gene transgenic lines and the double gene transgenic in terms of their ability to activate the plant defense system. Rice plants of each individual construct were screened via PCR, Southern hybridization, activity assays, and expression analysis. The best transgenic lines of each construct were chosen for comparative study. The fold change in qRT-PCR and activity assays revealed that the pyramided transgenic rice plants show a significant upregulation of defense-related genes, PR genes, and antioxidant marker genes as compared to the single transgene. Simultaneous co-expression of both the genes was found to be more efficient in tolerating oxidative stress. In R. solani (RS) toxin assay, mycelial agar disc bioassay, and in vivo plant bioassay, pyramided transgenic plant lines were more competent at restricting the pathogen development and enhancing sheath blight tolerance as compared to single gene transformants.
Intrusion of the Kuroshio into the South and East China Seas
Authors: Wu Chau-Ron , Wang You-Lin , Lin Yong-Fu , Chao Shenn-Yu
Published: August 2017

The northward-flowing Kuroshio often intrudes westward and modulates the water masses of the South and East China Seas. These intrusions transcend multiple scales in time and space, which we demonstrate here using various independent data sets. There are two hot spots of intrusion, one in the Luzon Strait and the other off northeast Taiwan, which occur synchronously when the upstream Kuroshio weakens during winter. Beyond seasonal time scales, the two intrusions were not synchronous during 1993–2013. While intrusions into the South China Sea echoed the Pacific Decadal Oscillation, the intrusion northeast of Taiwan decreased markedly before 2002 but regularly reached the shelf thereafter. This change was due to the influence of westward impingements of cyclonic eddies from the open ocean on the Kuroshio main stream in place of anticyclonic eddies. During 1993–2001, decreasing cyclonic eddy impingements moved the Kuroshio away from northeast Taiwan, weakening the Kuroshio intrusion onto the East China Sea shelf. Thereafter, enhanced cyclonic eddy impingement during 2002–2013 weakened the Kuroshio transport, moving it closer to the shelf and enhancing its intrusion into the East China Sea.
Repetitive motor cortex stimulation reinforces the pain modulation circuits of peripheral neuropathic pain
Authors: Cha Myeounghoon , Um Sun Woo , Kwon Minjee , Nam Taick Sang , Lee Bae Hwan
Published: August 2017

Recent evidence indicates that motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. However, the neural mechanisms underlying the attenuated hyperalgesia after MCS are not completely understood. In this study, we investigated the neural mechanism of the effects of MCS using an animal model of neuropathic pain. After 10 daily sessions of MCS, repetitive MCS reduced mechanical allodynia and contributed to neuronal changes in the anterior cingulate cortex (ACC). Interestingly, inhibition of protein kinase M zeta (PKMζ), a regulator of synaptic plasticity, in the ACC blocked the effects of repetitive MCS. Histological and molecular studies showed a significantly increased level of glial fibrillary acidic protein (GFAP) expression in the ACC after peripheral neuropathy, and neither MCS treatment nor ZIP administration affected this increase. These results suggest that repetitive MCS can attenuate the mechanical allodynia in neuropathic pain, and that the activation of PKMζ in the ACC may play a role in the modulation of neuropathic pain via MCS.
The Role of PGE2 in Alveolar Epithelial and Lung Microvascular Endothelial Crosstalk
Authors: Bärnthaler Thomas , Maric Jovana , Platzer Wolfgang , Konya Viktoria , Theiler Anna , Hasenöhrl Carina , Gottschalk Benjamin , Trautmann Sandra , Schreiber Yannick , Graier Wolfgang F. , Schicho Rudolf , Marsche Gunther , Olschewski Andrea , Thomas Dominique , Schuligoi Rufina , Heinemann Akos
Published: August 2017

Disruption of the blood-air barrier, which is formed by lung microvascular endothelial and alveolar epithelial cells, is a hallmark of acute lung injury. It was shown that alveolar epithelial cells release an unidentified soluble factor that enhances the barrier function of lung microvascular endothelial cells. In this study we reveal that primarily prostaglandin (PG) E2 accounts for this endothelial barrier-promoting activity. Conditioned media from alveolar epithelial cells (primary ATI-like cells) collected from BALB/c mice and A549 cells increased the electrical resistance of pulmonary human microvascular endothelial cells, respectively. This effect was reversed by pretreating alveolar epithelial cells with a cyclooxygenase-2 inhibitor or by blockade of EP4 receptors on endothelial cells, and in A549 cells also by blocking the sphingosine-1-phosphate1 receptor. Cyclooxygenase-2 was constitutively expressed in A549 cells and in primary ATI-like cells, and was upregulated by lipopolysaccharide treatment. This was accompanied by enhanced PGE2 secretion into conditioned media. Therefore, we conclude that epithelium-derived PGE2 is a key regulator of endothelial barrier integrity via EP4 receptors under physiologic and inflammatory conditions. Given that pharmacologic treatment options are still unavailable for diseases with compromised air-blood barrier, like acute lung injury, our data thus support the therapeutic potential of selective EP4 receptor agonists.
Facile fabrication of complex networks of memristive devices
Authors: Minnai Chloé , Bellacicca Andrea , Brown Simon A. , Milani Paolo
Published: August 2017

We describe the memristive properties of cluster-assembled gold films. We show that resistive switching is observed in pure metallic nanostructured films at room temperature and atmospheric pressure, in response to applied voltage inputs. In particular, we observe resistance changes up to 400% and archetypal switching events that have remarkable symmetry with the applied voltage. We associated this symmetry with ‘potentiation’ and ‘anti-potentiation’ processes involving the activation of synapses and of pathways comprising multiple synapses. The stability and reproducibility of the resistance switching, which lasted over many hours, make these devices ideal test-beds for exploration of the basic mechanisms of the switching processes, and allow convenient fabrication of devices that may have neuromorphic properties.
Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
Authors: Del Re Marzia , Vivaldi Caterina , Rofi Eleonora , Vasile Enrico , Miccoli Mario , Caparello Chiara , d’Arienzo Paolo Davide , Fornaro Lorenzo , Falcone Alfredo , Danesi Romano
Published: August 2017

Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled. Three ml of plasma were collected: 1) before starting chemotherapy (baseline); 2) at day 15 of treatment; and 3) at each clinical follow-up. cftDNA was extracted and analysed for KRAS mutations (mutKRAS) by digital droplet PCR. Nineteen patients displayed a mutKRAS in baseline plasma samples. There was a statistically significant difference in progression-free survival (PFS) and overall survival (OS) in patients with increase vs. stability/reduction of cftDNA in the sample collected at day 15 (median PFS 2.5 vs 7.5 months, p = 0.03; median OS 6.5 vs 11.5 months, p = 0.009). The results of this study demonstrate that cftDNA mutKRAS changes are associated with tumor response to chemotherapy and support the evidence that mutKRAS in plasma may be used as a new marker for monitoring treatment outcome and disease progression in PDAC.
Limits of radiomic-based entropy as a surrogate of tumor heterogeneity: ROI-area, acquisition protocol and tissue site exert substantial influence
Authors: Dercle Laurent , Ammari Samy , Bateson Mathilde , Durand Paul Blanc , Haspinger Eva , Massard Christophe , Jaudet Cyril , Varga Andrea , Deutsch Eric , Soria Jean-Charles , Ferté Charles
Published: August 2017

Entropy is a promising quantitative imaging biomarker for characterizing cancer imaging phenotype. Entropy has been associated with tumor gene expression, tumor metabolism, tumor stage, patient prognosis, and treatment response. Our hypothesis states that tumor-specific biomarkers such as entropy should be correlated between synchronous metastases. Therefore, a significant proportion of the variance of entropy should be attributed to the malignant process. We analyzed 112 patients with matched/paired synchronous metastases (SM#1 and SM#2) prospectively enrolled in the MOSCATO-01 clinical trial. Imaging features were extracted from Regions Of Interest (ROI) delineated on CT-scan using TexRAD software. We showed that synchronous metastasis entropy was correlated across 5 Spatial Scale Filters: Spearman’s Rho ranged between 0.41 and 0.59 (P = 0.0001, Bonferroni correction). Multivariate linear analysis revealed that entropy in SM#1 is significantly associated with (i) primary tumor type; (ii) entropy in SM#2 (same malignant process); (iii) ROI area size; (iv) metastasis site; and (v) entropy in the psoas muscle (reference tissue). Entropy was a logarithmic function of ROI area in normal control tissues (aorta, psoas) and in mathematical models (P < 0.01). We concluded that entropy is a tumor-specific metric only if confounding factors are corrected.
Acrodictys-like wood decay fungi from southern China, with two new families Acrodictyaceae and Junewangiaceae
Authors: Xia Ji Wen , Ma Ying Rui , Li Zhuang , Zhang Xiu Guo
Published: August 2017

During our continuous survey (2012–2016) of saprobic hyphomycetes from dead branches in the forest ecosystems of southern China, we collected several acrodictys-like species. Acrodictys-like species are characterized by darkly pigmented and muriform conidia produced from holoblastic conidiogenous cells on macronematous, mononematous, cylindrical and unbranched or infrequently branched conidiophores. Phylogenetic analyses of ncLSU, ncSSU, ITS and tub2 sequence data lead us to propose two novel families in Sordariomycetes, Acrodictyaceae and Junewangiaceae. In addition, a new species, Acrodictys hainanensis, two new combinations, Junewangia queenslandica and Distoseptispora martinii, three new Chinese records, Acrodictys liputii, A. peruamazonensis and Junewangia sphaerospora are introduced. Two names, Acrodictys globulosa and A. malabarica, are resurrected.
Pro- and anti-inflammatory responses of peripheral blood mononuclear cells induced by Staphylococcus aureus and Pseudomonas aeruginosa phages
Authors: Van Belleghem Jonas D. , Clement Frédéric , Merabishvili Maya , Lavigne Rob , Vaneechoutte Mario
Published: August 2017

The ability of bacteriophages to kill bacteria is well known, as is their potential use as alternatives to antibiotics. As such, bacteriophages reach high doses locally through infection of their bacterial host in the human body. In this study we assessed the gene expression profile of peripheral blood monocytes from six donors for twelve immunity-related genes (i.e. CD14, CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, IL10, LYZ, SOCS3, TGFBI and TNFA) induced by Staphylococcus aureus phage ISP and four Pseudomonas aeruginosa phages (i.e. PNM, LUZ19, 14-1 and GE-vB_Pae-Kakheti25). The phages were able to induce clear and reproducible immune responses. Moreover, the overall immune response was very comparable for all five phages: down-regulation of LYZ and TGFBI, and up-regulation of CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, SOCS3 and TNFA. The observed immune response was shown to be endotoxin-independent and predominantly anti-inflammatory. Addition of endotoxins to the highly purified phages did not cause an immune response comparable to the one induced by the (endotoxin containing) phage lysate. In addition, the use of an intermediate level of endotoxins tipped the immune response to a more anti-inflammatory response, i.e. up-regulation of IL1RN and a strongly reduced expression of CXCL1 and CXCL5.
Condition-Dependent Trade-Off Between Weapon Size and Immunity in Males of the European Earwig
Authors: Körner Maximilian , Vogelweith Fanny , Foitzik Susanne , Meunier Joël
Published: August 2017

Investigating the expression of trade-offs between key life-history functions is central to our understanding of how these functions evolved and are maintained. However, detecting trade-offs can be challenging due to variation in resource availability, which masks trade-offs at the population level. Here, we investigated in the European earwig Forficula auricularia whether (1) weapon size trades off with three key immune parameters – hemocyte concentration, phenoloxidase and prophenoloxidase activity - and whether (2) expression and strength of these trade-offs depend on male body condition (body size) and/or change after an immune challenge. Our results partially confirmed condition dependent trade-offs between weapon size and immunity in male earwigs. Specifically, we found that after an immune challenge, weapon size trades off with hemocyte concentrations in low-condition, but not in good-condition males. Contrastingly, weapon size was independent of pre-challenge hemocyte concentration. We also found no trade-off between weapon size and phenoloxidase activity, independent of body condition and immune challenge. Overall, our study reveals that trade-offs with sexual traits may weaken or disappear in good-condition individuals. Given the importance of weapon size for male reproductive success, our results highlight how low-condition individuals may employ alternative life-history investment strategies to cope with resource limitation.
Testing Association between Mixed Type Outcomes and Covariates Jointly by the Use of a Latent Variable
Authors: Zhu Jiayan , Zhang Wei , Li Qizhai , Li Zhengbang
Published: August 2017

Multiple outcomes are often collected simultaneously in biomedical fields in order to identify whether a continuous response and an ordinal response are associated with some covariates simultaneously. Here we propose a joint statistical model by the use of a latent variable underlying the ordinal response. Asymptotic results are obtained and a jointly test is proposed for testing the continuous response and the ordinal response are associated with some covariates simultaneously. Extensive simulations and real data analysis results indicate more efficient performances of the proposed method than that of the combined p-values method.
Genetic variations of HvP5CS1 and their association with drought tolerance related traits in barley (Hordeum vulgare L.)
Authors: Xia Yanshi , Li Ronghua , Bai Guihua , Siddique Kadambot H. M. , Varshney Rajeev K. , Baum Michael , Yan Guijun , Guo Peiguo
Published: August 2017

Delta-1-pyrroline-5-carboxylate synthase gene1 (P5CS1) is the key gene involved in the biosynthesis of proline and is significantly induced by drought stress. The exploration of genetic variation in HvP5CS1 may facilitate a better understanding of the mechanism of drought adaptation in barley. In the current study, 41 polymorphisms including 16 single nucleotide polymorphisms (SNPs) and 25 insertions/deletions (indels) were detected in HvP5CS1 among 287 barley (Hordeum vulgare L.) accessions collected worldwide, with 13 distinct haplotypes identified in the barley collection. Five polymorphisms in HvP5CS1 were significantly (P < 0.001) associated with drought tolerance related traits in barley. The phenotypic variation of a given trait explained by each associated polymorphism ranged from 4.43% to 9.81%. Two sequence variations that were significantly (P < 0.0001) associated with grain yield had marginally significant positive Tajima’s D values in the sliding window, so they might have been selected for environmental adaptation. Meanwhile, two haplotypes HvP5CS1_H1 and HvP5CS1_H4, which contained desired alleles of the two variations mentioned above, were significantly (P < 0.001) associated with drought tolerance related traits, and explained 5.00~11.89% of the phenotypic variations. These variations associated with drought tolerance related traits can be used as potential markers for improving drought tolerance in barley.
Effect of X-ray irradiation on hepatocarcinoma cells and erythrocytes in salvaged blood
Authors: Zhang Feng-Jiang , Yang Jin-Ting , Tang Li-Hui , Wang Wen-Na , Sun Kai , Ming Yue , Muhammad Kanhar Ghulam , Zheng Yin-Fei , Yan Min
Published: August 2017

The broad clinical acceptance of intraoperative blood salvage and its applications in cancer surgery remain controversial. Until now, a method that can safely eliminate cancer cells while preserving erythrocytes does not exist. Here, we investigated whether X-ray generated from linear accelerator irradiation at a certain dose can kill hepatocarcinoma cells while preserving erythrocytes. HepG2, SK-Hep1 or Huh7 cells were mixed into the aliquots of erythrocytes obtained from healthy volunteers. After the mixed cells were exposed to 30 Gy and 50 Gy X-rays irradiation, the viability, clonogenicity, DNA synthesis and tumorigenicity of the tumor cells were determined by the MTT assay, plate colony formation, 5-ethynyl-2′-deoxyuridine incorporation, and subcutaneous xenograft implantation into immunocompromised mice. The ATP, 2,3-DPG, free Hb, osmotic fragility, blood gas variables in erythrocytes and morphology of erythrocytes at 0 h, 12 h, 24 h, 48 h, 72 h after irradiation were analyzed. X-ray irradiation at 30 Gy effectively inhibited the viability, proliferation, and tumorigenicity of HepG2, SK-Hep1 and Huh7 cells without noticeably damaging the ability of oxygen-carrying, membrane integrity and morphology of erythrocytes. Theses results suggest that X-ray at 30 Gy irradiation might be safe to eliminate hepatocarcinoma cells while preserving erythrocytes in salvaged blood.
Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers
Authors: Neumann Kiel D. , Villanueva-Meyer Javier E. , Mutch Christopher A. , Flavell Robert R. , Blecha Joseph E. , Kwak Tiffany , Sriram Renuka , VanBrocklin Henry F. , Rosenberg Oren S. , Ohliger Michael A. , Wilson David M.
Published: August 2017

Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells (111In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells (18F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host. In this report, we exploited one key difference, bacterial cell wall biosynthesis, to detect living bacteria using a positron-labeled D-amino acid. After screening several 14C D-amino acids for their incorporation into E. coli in culture, we identified D-methionine as a probe with outstanding radiopharmaceutical potential. Based on an analogous procedure to that used for L-[methyl-11C]methionine ([11C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-11C]methionine ([11C] D-Met), and showed that it can rapidly and selectively differentiate both E. coli and S. aureus infections from sterile inflammation in vivo. We believe that the ease of [11C] D-Met radiosynthesis, coupled with its rapid and specific in vivo bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice.
Inhibition of hypoxic response decreases stemness and reduces tumorigenic signaling due to impaired assembly of HIF1 transcription complex in pancreatic cancer
Authors: McGinn Olivia , Gupta Vineet K. , Dauer Patricia , Arora Nivedita , Sharma Nikita , Nomura Alice , Dudeja Vikas , Saluja Ashok , Banerjee Sulagna
Published: August 2017

Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer. Minnelide has just completed Phase 1 trial against GI cancers and is currently awaiting Phase 2 trials. Our results showed that upon treatment with triptolide, HIF-1α protein accumulated in pancreatic cancer cells even though hypoxic response was decreased in them. Our studies showed even though HIF-1α is accumulated in the treated cells, there was no decrease in HIF-1 binding to hypoxia response elements. However, the HIF-1 transcriptional activity was significantly reduced owing to depletion of co-activator p300 upon treatment with triptolide. Further, treatment with triptolide resulted in a decreased activity of Sp1 and NF-kB the two major oncogenic signaling pathway in pancreatic cancer along with a decreased tumor initiating cell (TIC) population in pancreatic tumor.
Pulsed Laser Beam Welding of Pd43Cu27Ni10P20 Bulk Metallic Glass
Authors: Shao Ling , Datye Amit , Huang Jiankang , Ketkaew Jittisa , Woo Sohn Sung , Zhao Shaofan , Wu Sujun , Zhang Yuming , Schwarz Udo D. , Schroers Jan
Published: August 2017

We used pulsed laser beam welding method to join Pd43Cu27Ni10P20 (at.%) bulk metallic glass and characterized the properties of the joint. Fusion zone and heat-affected zone in the weld joint can be maintained completely amorphous as confirmed by X-ray diffraction and differential scanning calorimetry. No visible defects were observed in the weld joint. Nanoindentation and bend tests were carried out to determine the mechanical properties of the weld joint. Fusion zone and heat-affected zone exhibit very similar elastic moduli and hardness when compared to the base material, and the weld joint shows high ductility in bending which is accomplished through the operation of multiple shear bands. Our results reveal that pulsed laser beam welding under appropriate processing parameters provides a practical viable method to join bulk metallic glasses.
Mating-type genes of the anamorphic fungus Ulocladium botrytis affect both asexual sporulation and sexual reproduction
Authors: Wang Qun , Wang Shi , Xiong Chen Lin , James Timothy Y. , Zhang Xiu Guo
Published: August 2017

Ulocladium was thought to be a strictly asexual genus of filamentous fungi. However, Ulocladium strains were shown to possess both MAT1-1-1 and MAT1-2-1 genes as observed in homothallic filamentous Ascomycetes. Here, we demonstrate that the U. botrytis MAT genes play essential roles for controlling asexual traits (conidial size and number). Using reciprocal genetic transformation, we demonstrate that MAT genes from the related heterothallic species Cochliobolus heterostrophus can also influence U. botrytis colony growth, conidial number and size, and have a strong effect on the range of the number of septa/conidium. Moreover, U. botrytis MAT genes can also affect similar aspects of asexual reproduction when expressed in C. heterostrophus. Heterologous complementation using C. heterostrophus MAT genes shows that they have lost the ability to regulate sexual reproduction in U. botrytis, under the conditions we employed, while the reciprocal heterologous complementation demonstrates that U. botrytis MAT genes have the ability to partially induce sexual reproduction in C. heterostrophus. Thus, the genetic backgrounds of C. heterostrophus and U. botrytis play significant roles in determining the function of MAT genes on sexual reproduction in these two fungi species. These data further support the role of MAT genes in controlling asexual growth in filamentous Ascomycetes but also confirm that heterothallic and homothallic Dothideomycete fungi can be interconverted by the exchange of MAT genes.
Investigation into the stability and culturability of Chinese enterotypes
Authors: Yin Yeshi , Fan Bin , Liu Wei , Ren Rongrong , Chen Huahai , Bai Shaofeng , Zhu Liying , Sun Gang , Yang Yunsheng , Wang Xin
Published: August 2017

Although many gut microbial enterotypes have been reported in Europe, Africa and the U.S., their effects on human health are still not yet clear. Culturing gut microbial enterotypes in vitro will be helpful to study their effects and applications. Here, fecal samples from 13 healthy Chinese volunteers were collected and subjected to next-generation sequencing. The results showed that seven of these samples belong to the Bacteroides enterotype and another six to the Prevotella enterotype. Stability of these Chinese gut microbial enterotypes was also evaluated. Results showed that most of the tested volunteer gut microbiota to be very stable. For one volunteer, the bacterial community returned to the state it was in before intestinal lavage and antibiotics treatment after four months. XP medium was found effective for simulating the Bacteroides enterotype independent of the original gut microbial community in an in vitro chemostat culture system. Although, the Prevotella enterotype was not very well simulated in vitro, different culture elements selectively enriched different gut bacteria. Pectin and xylan were found to be related to the enrichment of the genera Bacteroides, Sutterella, and Flavonifractor in this chemostat culture system.
Exercise leads to unfavourable cardiac remodelling and enhanced metabolic homeostasis in obese mice with cardiac and skeletal muscle autophagy deficiency
Authors: Yan Zhen , Kronemberger Ana , Blomme Jay , Call Jarrod A. , Caster Hannah M. , Pereira Renata O. , Zhao Henan , de Melo Vitor U. , Laker Rhianna C. , Zhang Mei , Lira Vitor A.
Published: August 2017

Autophagy is stimulated by exercise in several tissues; yet the role of skeletal and cardiac muscle-specific autophagy on the benefits of exercise training remains incompletely understood. Here, we determined the metabolic impact of exercise training in obese mice with cardiac and skeletal muscle disruption of the Autophagy related 7 gene (Atg7h&mKO). Muscle autophagy deficiency did not affect glucose clearance and exercise capacity in lean adult mice. High-fat diet in sedentary mice led to endoplasmic reticulum stress and aberrant mitochondrial protein expression in autophagy-deficient skeletal and cardiac muscles. Endurance exercise training partially reversed these abnormalities in skeletal muscle, but aggravated those in the heart also causing cardiac fibrosis, foetal gene reprogramming, and impaired mitochondrial biogenesis. Interestingly, exercise-trained Atg7h&mKO mice were better protected against obesity and insulin resistance with increased circulating fibroblast growth factor 21 (FGF21), elevated Fgf21 mRNA and protein solely in the heart, and upregulation of FGF21-target genes involved in thermogenesis and fatty acid oxidation in brown fat. These results indicate that autophagy is essential for the protective effects of exercise in the heart. However, the atypical remodelling elicited by exercise in the autophagy deficient cardiac muscle enhances whole-body metabolism, at least partially, via a heart-brown fat cross-talk involving FGF21.
Global assessment of flood and storm extremes with increased temperatures
Authors: Wasko Conrad , Sharma Ashish
Published: August 2017

There is overwhelming consensus that the intensity of heavy precipitation events is increasing in a warming world. It is generally expected such increases will translate to a corresponding increase in flooding. Here, using global data sets for non-urban catchments, we investigate the sensitivity of extreme daily precipitation and streamflow to changes in daily temperature. We find little evidence to suggest that increases in heavy rainfall events at higher temperatures result in similar increases in streamflow, with most regions throughout the world showing decreased streamflow with higher temperatures. To understand why this is the case, we assess the impact of the size of the catchment and the rarity of the event. As the precipitation event becomes more extreme and the catchment size becomes smaller, characteristics such as the initial moisture in the catchment become less relevant, leading to a more consistent response of precipitation and streamflow extremes to temperature increase. Our results indicate that only in the most extreme cases, for smaller catchments, do increases in precipitation at higher temperatures correspond to increases in streamflow.