bluuebunny/crossref_metadata_2025 huggingface dataset:
A Non‐Pt Electronically Coupled Semiconductor Heterojunction for Enhanced Oxygen Reduction Electrocatalytic Property
Authors: Li Fan , Qin Yong , Chalgin Aleksei , Gu Xin , Chen Wenlong , Ma Yanling , Xiang Qian , Wu Yi , Shi Fenglei , Zong Yuan , Tao Peng , Song Chengyi , Shang Wen , Deng Tao , Zhu Hong , Wu Jianbo
Published: May 2019

Hybrid faceted‐Ag3PO4/cube‐Cu2O composite materials have been fabricated and employed as oxygen reduction electrocatalysts for proton exchange membrane fuel cells (PEMFCs). The charge separation effect via the formation of PN junction has been demonstrated to boost the electrocatalysis toward oxygen reduction reaction. The as‐prepared rhombic dodecahedron‐Ag3PO4/cube‐Cu2O/C hybrid catalyst shows a mass‐specific activity of 109.80 mA/mgAg, which is about 6.4 times that of pure rhombic dodecahedron‐Ag3PO4/C catalyst (17.20 mA/mgAg). The density functional theory (DFT) calculation based on the density of states (DOS) further proved the optimal tunable effect, which is in pace with demonstration of electron transfer direction revealed by X‐ray photoelectron spectroscopy (XPS) analysis. Our work establishes a theoretical and practical basis for the rational design of newly non‐Pt hybrid catalysts, moreover, advances the future efficient application of PEMFCs.
Bimetallic Ni‐Co Silicate Hollow Spheres with Controllable Morphology for the Application on Supercapacitor
Authors: Dong Fengying , Liu Xiaojuan , Sun Xinzhi
Published: May 2019

A facile and one‐step synthetic method is developed to produce the layered bimetallic Ni−Co silicate with the controllable morphology and porous microstructure by using the silica as the sacrifice template at the moderate reaction conditions. The bimetallic Ni−Co silicate core‐shell and hollow spheres were obtained under 140 °C for 6 h and 12 h, respectively. The pore size and the content of metal ions of the bimetallic Ni−Co silicate could be affected by the different structure. The final product shows good dispersivity, which is benefit to the homogeneity as an active material in the electrode. The as‐prepared Ni−Co silicate hollow spheres exhibit good electrochemical performance with high specific capacitance and rate capability, good charge‐discharge stability and long cycle life. The capacitance retention of the hollow structure can reach 58.69% at the current density of 10 A/g and 86.38% after 5000 cycle. The good electrochemical performance can be attributed to the different size of the pores and layer architecture. Bimetallic Ni−Co silicate hollow spheres show better electrochemical properties than the monometallic Ni or Co, which attribute to the synergistic effect.
Synthesis and Evaluation of Enalapril‐Loaded PVA/PMC Modified Magnetic Nanoparticles as a Novel Efficient Nano‐Carrier
Authors: Shahverdi Negin , Heydarinasab Amir , Panahi Homayon Ahmad , Moniri Elham
Published: May 2019

In the present study, the development of new Enalapril‐loaded adsorbent and evaluation of drug release was studied in vitro. Initially, Fe3O4 magnetic nanoparticles were synthesized via co‐precipitation method. Then, the mixture of polymers was deposited on the surface of the magnetic nanoparticles via radical polymerization in order to enhance the adsorption capacity of nanoparticles with biocompatible poly methylcellulose modified with polyvinyl alcohol. The equilibrium adsorption data magnetite nano‐sorbent were analyzed using Langmuir, Freundlich, and Temkin. The drug‐release study showed that 80% of Enalapril released in the simulated gastrointestinal environment for 18 hours. The samples and products analyzed by FTIR, elemental analysis, thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). Adsorption parameters such as pH, temperature and contact time were optimized, and Langmuir, Freundlich and Temkin's isotherms were studied for the drug adsorption mechanism. The release process of Enalapril studied in the simulated human digestive environment. The release profile of Enalapril has a very steep slope for 30 minutes in the simulated human gastric.
Insights into the Fluorescence Sensing Mechanism of Scandium‐Based Metal‐Organic Frameworks by Solid‐State NMR Spectroscopy
Authors: Xie Chang , Yu Zhiwu , Tong Wei , Shehzad Khurram , Xu Weihong , Wang Junfeng , Liu Jinhuai
Published: May 2019

Fluorescent metal‐organic frameworks (MOFs) have been evolved as a class of promising materials for sensing application. However, it is still a challenging issue to understand the sensing mechanism of luminescent MOFs interacting with analyte species from molecule level. Herein, fluorescent Sc2(NH2‐BDC)3 crystals are prepared as a probe. The compositional and structural characteristics of the obtained product are systematically characterized. Sc2(NH2‐BDC)3 shows admirable thermal and chemical stability in different solvents and aqueous solutions with diverse pH values. It shows excellent fluorescence sensing behaviors towards Co2+ and Ni2+ ions through fluorescence quenching effect. The sensing mechanism of Sc2(NH2‐BDC)3 towards heavy metal ions is elucidated via X‐ray photoelectron spectroscopy (XPS) analyses, Fourier transform infrared (FTIR) spectroscopy analyses, solid‐state NMR (ssNMR) spectra and electron paramagnetic resonance (EPR) analyses. The as‐prepared Sc2(NH2‐BDC)3 crystals contain some defects with formation of scandium hydroxyls in the crystal structure from the evidence analyzed by ssNMR and EPR, which are inclined to interact with Co2+ and Ni2+ ions, leading to the fluorescent quenching. This research not only demonstrates the understanding of the sensing mechanism of luminescent MOFs from molecular level, but also highlights the design of functionalized MOFs for fluorescent sensing.
Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex
Authors: Askew Caitlin E. , Lopez Alberto J. , Wood Marcelo A. , Metherate Raju
Published: May 2019

Nicotine activates nicotinic acetylcholine receptors and improves cognitive and sensory function, in part by its actions in cortical regions. Physiological studies show that nicotine amplifies stimulus‐evoked responses in sensory cortex, potentially contributing to enhancement of sensory processing. However, the role of specific cell types and circuits in the nicotinic modulation of sensory cortex remains unclear. Here, we performed whole‐cell recordings from pyramidal (Pyr) neurons and inhibitory interneurons expressing parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) in mouse auditory cortex, in vitro. Bath application of nicotine strongly depolarized and excited VIP neurons, weakly depolarized Pyr neurons, and had no effect on the membrane potential of SOM or PV neurons. The use of receptor antagonists showed that nicotine's effects on VIP and Pyr neurons were direct and indirect, respectively. Nicotine also enhanced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in Pyr, VIP, and SOM, but not PV, cells. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we show that chemogenetic inhibition of VIP neurons prevents nicotine's effects on Pyr neurons. Since VIP cells preferentially contact other inhibitory interneurons, we suggest that nicotine drives VIP cell firing to disinhibit Pyr cell somata, potentially making Pyr cells more responsive to auditory stimuli. In parallel, activation of VIP cells also directly inhibits Pyr neurons, likely altering integration of other synaptic inputs. These cellular and synaptic mechanisms likely contribute to nicotine's beneficial effects on cognitive and sensory function.
A new path to the non blow-up of incompressible flows
Authors: Agélas Léo
Published: May 2019

One of the most challenging questions in fluid dynamics is whether the three-dimensional (3D) incompressible Navier-Stokes, 3D Euler and two-dimensional Quasi-Geostrophic (2D QG) equations can develop a finite-time singularity from smooth initial data. Recently, from a numerical point of view, Luo & Hou presented a class of potentially singular solutions to the Euler equations in a fluid with solid boundary [1,2]. Furthermore, in two recent papers [3,4], Tao indicates a significant barrier to establishing global regularity for the 3D Euler and Navier-Stokes equations, in that any method for achieving this, must use the finer geometric structure of these equations. In this paper, we show that the singularity discovered by Luo & Hou which lies right on the boundary is not relevant in the case of the whole domain

\mathbb{R}^{3}

. We reveal also that the translation and rotation invariance present in the Euler, Navier-Stokes and 2D QG equations are the key for the non blow-up in finite time of the solutions. The translation and rotation invariance of these equations combined with the anisotropic structure of regions of high vorticity allowed to establish a new geometric non blow-up criterion which yield us to the non blow-up of the solutions in all the Kerr's numerical experiments and to show that the potential mechanism of blow-up introduced in [5] cannot lead to the blow-up in finite time of solutions of Euler equations.
Nudes are Forever: Judicial Interpretations of Digital Technology’s Impact on “Revenge Porn”
Authors: Dodge Alexa
Published: May 2019

In this article I explore judicial interpretations of the relationship between digital technology and non-consensual intimate image distribution (NCIID) (i.e., “revenge porn”). Drawing on my analysis of forty-nine Canadian cases of NCIID, I show that judicial interpretations of digital technology have important influences on how NCIID is understood and responded to in the law. I find that the majority of judges perceive digital technology as making NCIID easier to commit—with the simple “click of a mouse”—and as increasing the amount of harm caused by this act—as digital nude/sexual photos are seen as lasting “forever” and thus as resulting in ongoing and immeasurable harm to victims. These perceptions have substantive impacts on legal rationales and sentencing decisions, with the affordances of digital technology regularly being treated as justifying harsher sentences to denounce and deter this act.
Absence of Herbicide Cross-Resistance in Two Atrazine-Resistant Velvetleaf (Abutilon theophrasti) Biotypes
Authors: Gray James A. , Stoltenberg David E. , Balke Nelson E.
Published: May 2019

Field and greenhouse research was conducted to quantify the level of resistance to atrazine in Wisconsin (WRB1) and Maryland (MRB) velvetleaf biotypes and to determine cross-resistance of the WRB1 and MRB biotypes to other selected herbicides as compared to a Wisconsin atrazine-susceptible velvetleaf accession (WSA1). In field studies, the WRB1 and MRB biotypes survived atrazine applied POST at dosages as high as 4.5 kg ha−1. In contrast, the WSA1 accession had 50% survival following a 1.1 kg ha−1POST atrazine application. The WRB1 biotype demonstrated neither cross-resistance nor negative cross-resistance to alachlor, bentazon, bromoxynil, cyanazine, dicamba, linuron, metribuzin, or thifensulfuron. The MRB biotype demonstrated neither cross-resistance nor negative cross-resistance to alachlor, bentazon, dicamba, metribuzin, or thifensulfuron; slight negative cross-resistance was demonstrated to bromoxynil, cyanazine, and linuron. In greenhouse studies, the WRB1 and MRB biotypes were approximately 100-fold more resistant to atrazine than the WSA1 accession; the WRB1 and MRB biotypes demonstrated neither cross-resistance nor negative cross-resistance to alachlor, ametryn, bentazon, bromoxynil, cyanazine, dicamba, linuron, metribuzin, pendimethalin, terbacil, or thifensulfuron. Absence of cross-resistance to cyanazine, ametryn, metribuzin, and terbacil in the WRB1 and MRB biotypes of velvetleaf is in contrast to most other atrazine-resistant weed biotypes.
Adsorption Characteristics of Atrazine and Alachlor in Kansas Soils
Authors: Sonon Leticia S. , Schwab A. Paul
Published: May 2019

The adsorption of atrazine and alachlor was studied on samples of three horizons from soils with different textures and organic carbon contents. Soils were equilibrated with five concentrations of atrazine and alachlor using batch techniques. Adsorption affinity for atrazine and alachlor was approximated by the Freundlich constant (Kf), distribution coefficient (Kd), and the normalizedKdbased on organic carbon (Koc). Adsorption was not significantly correlated with soil depth, clay content, or organic carbon. Atrazine adsorption was a linear function of equilibrium concentration for nearly all soil horizons but was nonlinear in most horizons for alachlor. The extent of atrazine adsorption was greater in all horizons of the fine-textured soils (Kd= 1.5 to 5.5) compared to coarse-textured soils (Kd= 0.40 to 0.87). The same general trends with texture were not apparent for alachlor. Conversion ofKdtoKocfailed to reduce the variability in the linear adsorption coefficient for atrazine and alachlor in the different soils of this study.
Magnitude of Imazethapyr Resistance of Corn (Zea mays) Hybrids with Altered Acetolactate Synthase
Authors: Currie Randall S. , Kwon Chae S. , Penner Donald
Published: May 2019

A laboratory study was conducted to evaluate the magnitude of imazethapyr resistance of field corn hybrids with altered acetolactate synthase (ALS) by comparing the responses of ALS extracted from homozygous and heterozygous resistant corn to nicosulfuron, primisulfuron, and imazethapyr. ALS isolated from Pioneer 3162 IR, Pioneer 3180 IR, Pioneer 3377 IR, and Ciba 4393 RSC hybrids was much more resistant to inhibition by these herbicides than ALS from the hybrids Pioneer 3162, Pioneer 3180, Pioneer 3377, and Ciba 4393, and the public inbred LH 74. Corn hybrids heterozygous for the Pioneer resistance gene were intermediate in response to the herbicides. ALS from ICI 8532 IT was resistant to imazethapyr but not to primisulfuron or nicosulfuron. The level of resistance of ALS from ICI 8532 IT was similar to that of ALS from Pioneer 3162 IR x Pioneer 3162 and Pioneer 3180 IR x Pioneer 3180 crosses that were also heterozygous for the resistance gene.
MSMA and Pyrithiobac Effects on Cotton (Gossypium hirsutum) Development, Yield and Quality
Authors: Shankle Mark W. , Hayes Robert M. , Reich Vernon H. , Mueller Thomas C.
Published: May 2019

Field research was conducted in Tennessee at Jackson in 1991 and at Milan in 1992 to compare the effect of MSMA and pyrithiobac on cotton development, yield, and quality. In separate treatments to different plots, pyrithiobac at 0.14 kg ai ha–1did not affect development, yield, and quality of cotton. MSMA at 2.24 kg ai ha–1decreased cotton plant internode length 10 to 15% and height by 15% 5 wk after late treatment both years. MSMA applied to 50 cm cotton reduced subsequent plant height in 1992, but other plant characteristics were not affected. In 1991, MSMA increased squares and decreased blooms and bolls for monopodia and sympodia position one and two, which suggested a delay in plant development. In 1991, mechanical harvest lint yields were decreased by MSMA at first harvest while increasing second harvest lint yields. However, in 1991 only MSMA applied late decreased total harvest lint yield 20%. Plant mapping data determined that the yield decrease was a result of decreased yields at sympodia positions one and two. Cotton seed arsenic analysis indicated that MSMA-late increased arsenic levels by ≈ 1 ppmw in 1991 for sympodia at position one and two compared to the untreated check, while position two contained the highest level of 1.8 ppmw.
Influence of Nontarget Neighbors and Spray Volume on Retention and Efficacy of Triclopyr in Purple Loosestrife (Lythrum salicaria)
Authors: Stamm Katovich Elizabeth J. , Becker Roger L. , Kinkaid Brad D.
Published: May 2019

Greenhouse studies were conducted to determine the influence of plant density and spray volume on the retention, spray deposition, efficacy, and translocation of the amine salt of triclopyr in purple loosestrife. More spray solution was retained on leaves at 935 Lha−1than at 94 Lha−1at populations of 0, 4, or 8 nontarget neighbors. Spray coverage decreased with decreasing height within the plant canopy when spray cards were placed in the top, middle, and soil surface adjacent to the central target plant. Within a population, spray card coverage generally increased as spray volume increased. Regrowth from the crown was affected by spray volume, and uniform spray coverage of the plant was required for adequate control of vegetative regrowth and was achieved with spray volumes of 374 and 935 L ha−1spray volume. Regrowth of purple loosestrife was greater at 94 Lha−1at all three plant populations indicating that less herbicide penetrated the canopy to reach the basal portion of the plant. A laboratory experiment was conducted to investigate the translocation of radiolabelled triclopyr to roots and crowns of purple loosestrife. Only 0.3 to 1.4% of absorbed14C-labelled material was translocated to roots and crowns. Low spray volumes and dense stands of purple loosestrife would likely result in poor control because inadequate amounts of triclopyr reach the basal portion of the plant and translocate to vegetative propagules.
Using Spatial Information Technologies to Map Chinese Tamarisk (Tamarix chinensis) Infestations
Authors: Everitt James H. , Escobar David E. , Alaniz Mario A. , Davis Michael R. , Richerson James V.
Published: May 2019

This paper describes the application of airborne video data with global positioning system and geographic information system technologies for detecting and mapping Chinese tamarisk infestations in the southwestern United States. Study areas were along the Colorado River in southwestern Arizona, the Rio Grande River in extreme west Texas, and the Pecos River in west-central Texas. Chinese tamarisk could be readily distinguished on conventional color video imagery in late November when its foliage turned a yellow-orange to orange-brown color prior to leaf drop. The integration of the global positioning system with the video imagery permitted latitude/longitude coordinates of Chinese tamarisk infestations to be recorded on each image. The global positioning system latitude/longitude coordinates were entered into a geographic information system to map Chinese tamarisk populations along the three river systems.
Two procedures for training a novel second language phonetic contrast
Authors: Flege James Emil
Published: May 2019

Native speakers of Mandarin who learn English as a second language (L2) frequently misidentify unreleased tokens of /t/ and /d/ in the final position of English words. The purpose of this study was to evaluate two training methods that might be used to increase Mandarin adults’ accuracy in identifying such stops. Subjects were assigned to receive training using a two-alternative forced-choice procedure or a categorical same/different discrimination procedure. Small but significant increases in the percentage of correct identifications of /t/ and /d/ tokens were obtained for both groups of native Mandarin subjects, although their gains did not differ significantly. These gains were still evident for both groups 2 months after completing the training. The effect of training for both groups generalized to words that were not used in training. Contrary to the hypothesis that identification training promotes more robust long-term memory representations than same/different training, the magnitude of generalization observed for the two groups did not differ significantly. However, subjects seemed to maintain the effects of the same/different training better than the effects of the identification training. Taken together, the results obtained here challenge the view that identification training is superior to same/different training as a means for training novel phonetic contrasts.
The New Barter Economy: An Appraisal of Local Exchange and Trading Systems (LETS)
Authors: Williams Colin C.
Published: May 2019

A new form of barter economy is emerging in many industrial nations. People are exchanging goods and services through Local Exchange and Trading Systems (LETS). These are local associations whose members list their offers of, and requests for, goods and services in a directory and then exchange them priced in a local unit of currency. Using a United Kingdom case study of Totnes LETS, this paper presents a preliminary appraisal of their economic, social equity and community-building objectives. It finds that although LETS are fulfilling these objectives, achievements could be substantially improved with some alterations in public policy towards LETS.
Tuberculosis in the Workplace: OSHA's Compliance Experience
Authors: McDiarmid Melissa , Gamponia Melissa J. , Ryan Margaret A.K. , Hirshon Jon Mark , Gillen N.A. , Cox Maureen
Published: May 2019

Objective:

Inspections of 272 facilities were performed between May 1992 and October 1994 to determine compliance with applicable Occupational Safety and Health Administration (OSHA) requirements for prevention of tuberculosis (TB) transmission.

Design:

Retrospective record review of two data sources: (1) OSHA's Computerized Integrated Management Information System and (2) an inspector-completed questionnaire on inspection results.

Setting/Participants:

Inspections of five types of facilities: healthcare institutions, correctional facilities, homeless shelters, long-term–care facilities for the elderly, and others, including drug treatment centers that the Centers for Disease Control and Prevention (CDC) identified as having a higher than expected rate of TB.

Methods:

The OSHA Compliance Memorandum, based on the 1990 CDC Guidelines, which outlined elements of a TB prevention program, was used in performing 272 inspections of facilities between May 1992 and October 1994. Elements of compliance were recorded and reviewed from the IMIS database and inspectors' questionnaires.

Results:

Regulated facilities were not fully compliant with OSHA guidance. Generally, healthcare facilities performed better than other facilities. Most facilities (79%) were compliant with administrative elements of a comprehensive TB control program, such as early identification of known or suspected infectious TB patients and skin testing of workers. Only 29% of inspected facilities were found to have acceptable respiratory protection programs for the prevention of occupational TB.

Conclusion:

Facilities have not been fully compliant with the OSHA memorandum describing protection of workers from TB. Facility compliance was better with some traditionally recognized TB infection control elements, but was weaker in the area of respiratory protection programs. This may reflect a lack of familiarity with the latter type of hazard protection.
Staphylococcus aureusBacteremia: Factors Predicting Hospital Mortality
Authors: Mylotte Joseph M. , Aeschlimann Jeffrey R. , Rotella Denise L.
Published: May 2019

Among 89 episodes ofStaphylococcus aureusbacteremia, factors identified as independent predictors of hospital mortality were Acute Physiology and Chronic Health Evaluation III score >60 (odds ratio [OR], 3.2; 95% confidence inter val [CI95], 1.7 to 5.9) and Lifestyle score >1 (OR, 2.1; CI95, 1.2 to 3.6). Future studies ofS aureusbacteremia should take into consideration acute severity of illness (as well as treatment and source of infection) when evaluating outcome.
Educational Needs and Opportunities for the Hospital Epidemiologist
Authors: Dembry Louise M. , Hierholzer Walter J.
Published: May 2019

The role of the hospital epidemiologist has changed substantially over the last 30 years as medical care has become more complex. The hospital epidemiologist needs training in methods for sur veillance, prevention, and control of nosocomial infections. The hospital epidemiologist also must know how to apply these methods to other areas, including the epidemiology of noninfectious adverse out-comes of medical care. Training in hospital epidemiology should be a defined part of every infectious disease fellowship training program. Ancillary and additional training is available from several sources.
The Role of Colonization in the Pathogenesis of Nosocomial Infections
Authors: Bonten Marc J.M. , Weinstein Robert A.
Published: May 2019

The close relationship between colonization and the development of nosocomial infections has been demonstrated. Patient-related factors, such as underlying illness for all major sites of infection and advanced age, and pathogen-related factors, such as the ability of bacteria to adhere to epithelial cells, play the major roles in the pathogenesis of colonization. However, exact mechanisms of colonization have not been elucidated, and modulation of bacterial adherence as a method of infection prevention remains experimental. Current methods of infection prevention, therefore, focus either on preventing growth of colonizing microorganisms or on preventing patient-pathogen contact. Topical antibiotics have been used as a method of colonization prevention. However, their effectiveness may be limited by increases in antibiotic resistance; moreover, the effects on patient outcome are controversial. Maintenance of the physiologic mucosal environment using nonantimicrobial agents seems a promising approach, but only a few studies demonstrating efficacy have been published. Prevention of colonization still must rely heavily on basic infection control measures to prevent contact between patient and pathogen.
Self‐Affine Fractal Spatial and Temporal Variability of the San Pedro River, Southern Arizona
Authors: Williams Z. C. , Pelletier J. D. , Meixner T.
Published: May 2019

Prevailing mathematical models of alluvial channel evolution generate smooth, idealized longitudinal profiles. Alluvial channel longitudinal profiles in nature, however, have substantial multiscale spatial and temporal variability. In this paper we quantify the spatial and temporal hydrologic and geomorphic variability of a 90‐km‐long reach of the San Pedro River (San Pedro River) in southeastern Arizona and compare that variability to numerical models designed specifically to honor the spatial and temporal variability of alluvial channel systems in nature. A key motivation of this work is the power law frequency size distribution of wet and dry reaches observed in the San Pedro River. We demonstrate that such a distribution is consistent with self‐affine fractal variations of the depth to bedrock and the channel longitudinal profile. At large spatial scales, spatial variations in depth to bedrock control the accommodation space for groundwater, which, in turn, controls spatial variations in surface water discharge. At small spatial scales, the longitudinal profile controls spatial variations in surface water discharge by changing the distance between the channel bed and the water table. These results underscore the complex spatiotemporal behavior of dryland alluvial rivers and the tight coupling that is possible between hydrologic and geomorphic processes in such systems.
Synthetic biology strategies for microbial biosynthesis of plant natural products
Authors: Cravens Aaron , Payne James , Smolke Christina D.
Published: May 2019

Metabolic engineers endeavor to create a bio-based manufacturing industry using microbes to produce fuels, chemicals, and medicines. Plant natural products (PNPs) are historically challenging to produce and are ubiquitous in medicines, flavors, and fragrances. Engineering PNP pathways into new hosts requires finding or modifying a suitable host to accommodate the pathway, planning and implementing a biosynthetic route to the compound, and discovering or engineering enzymes for missing steps. In this review, we describe recent developments in metabolic engineering at the level of host, pathway, and enzyme, and discuss how the field is approaching ever more complex biosynthetic opportunities.
Collagen-rich airway smooth muscle cells are a metastatic niche for tumor colonization in the lung
Authors: Lee Yu-Cheng , Kurtova Antonina V. , Xiao Jing , Nikolos Fotis , Hayashi Kazukuni , Tramel Zoe , Jain Antrix , Chen Fengju , Chokshi Mithil , Lee Ciaran , Bao Gang , Zhang Xiang , Shen Jianjun , Mo Qianxing , Jung Sung Yun , Rowley David , Chan Keith Syson
Published: May 2019

Metastases account for the majority of cancer deaths. While certain steps of the metastatic cascade are well characterized, identification of targets to block this process remains a challenge. Host factors determining metastatic colonization to secondary organs are particularly important for exploration, as those might be shared among different cancer types. Here, we showed that bladder tumor cells expressing the collagen receptor, CD167a, responded to collagen I stimulation at the primary tumor to promote local invasion and utilized the same receptor to preferentially colonize at airway smooth muscle cells (ASMCs)—a rich source of collagen III in lung. Morphologically, COL3-CD167a-driven metastatic foci are uniquely distinct from typical lung alveolar metastatic lesions and exhibited activation of the CD167a-HSP90-Stat3 axis. Importantly, metastatic lung colonization could be abrogated using an investigational drug that attenuates Stat3 activity, implicating this seed-and-soil interaction as a therapeutic target for eliminating lung metastasis.
Highly sensitive CE-ESI-MS analysis of N-glycans from complex biological samples
Authors: Lageveen-Kammeijer Guinevere S. M. , de Haan Noortje , Mohaupt Pablo , Wagt Sander , Filius Mike , Nouta Jan , Falck David , Wuhrer Manfred
Published: May 2019

The in-depth, high-sensitivity characterization of the glycome from complex biological samples, such as biofluids and tissues, is of utmost importance in basic biological research and biomarker discovery. Major challenges often arise from the vast structural diversity of glycans in combination with limited sample amounts. Here, we present a method for the highly sensitive characterization of released N-glycans by combining a capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) approach with linkage-specific derivatization of sialic acids and uniform cationic reducing end labelling of all glycans. This method allows the analysis of glycans at the attomole level, provides information on sialic acid isomers and enables the in-depth characterization of complex samples, even when available in minute amounts.
A RASSF1A-HIF1α loop drives Warburg effect in cancer and pulmonary hypertension
Authors: Dabral Swati , Muecke Christian , Valasarajan Chanil , Schmoranzer Mario , Wietelmann Astrid , Semenza Gregg L. , Meister Michael , Muley Thomas , Seeger-Nukpezah Tamina , Samakovlis Christos , Weissmann Norbert , Grimminger Friedrich , Seeger Werner , Savai Rajkumar , Pullamsetti Soni S.
Published: May 2019

Hypoxia signaling plays a major role in non-malignant and malignant hyperproliferative diseases. Pulmonary hypertension (PH), a hypoxia-driven vascular disease, is characterized by a glycolytic switch similar to the Warburg effect in cancer. Ras association domain family 1A (RASSF1A) is a scaffold protein that acts as a tumour suppressor. Here we show that hypoxia promotes stabilization of RASSF1A through NOX-1- and protein kinase C- dependent phosphorylation. In parallel, hypoxia inducible factor-1 α (HIF-1α) activates RASSF1A transcription via HIF-binding sites in the RASSF1A promoter region. Vice versa, RASSF1A binds to HIF-1α, blocks its prolyl-hydroxylation and proteasomal degradation, and thus enhances the activation of the glycolytic switch. We find that this mechanism operates in experimental hypoxia-induced PH, which is blocked in RASSF1A knockout mice, in human primary PH vascular cells, and in a subset of human lung cancer cells. We conclude that RASSF1A-HIF-1α forms a feedforward loop driving hypoxia signaling in PH and cancer.
Worldwide measurements of bioturbation intensity, ventilation rate, and the mixing depth of marine sediments
Authors: Solan Martin , Ward Ellie R. , White Ellen L. , Hibberd Elizabeth E. , Cassidy Camilla , Schuster Jasmin M. , Hale Rachel , Godbold Jasmin A.
Published: May 2019

The activities of a diverse array of sediment-dwelling fauna are known to mediate carbon remineralisation, biogeochemical cycling and other important properties of marine ecosystems, but the contributions that different seabed communities make to the global inventory have not been established. Here we provide a comprehensive georeferenced database of measured values of bioturbation intensity (Db, n = 1281), burrow ventilation rate (q, n = 765, 47 species) and the mixing depth (L, n = 1780) of marine soft sediments compiled from the scientific literature (1864–2018). These data provide reference information that can be used to inform and parameterise global, habitat specific and/or species level biogeochemical models that will be of value within the fields of geochemistry, ecology, climate, and palaeobiology. We include metadata relating to the source, timing and location of each study, the methodology used, and environmental and experimental information. The dataset presents opportunity to interrogate current ecological theory, refine functional typologies, quantify uncertainty and/or test the relevance and robustness of models used to project ecosystem responses to change.
In utero infection of Zika virus leads to abnormal central nervous system development in mice
Authors: Zhang Wei , Tan Yong Wah , Yam Wan Keat , Tu Haitao , Qiu Lifeng , Tan Eng King , Chu Justin Jang Hann , Zeng Li
Published: May 2019

The World Health Organization has declared ZIKA virus (ZIKV) a global public health emergency, prompted by the association of ZIKV infections with severe brain abnormalities in the human fetus. ZIKV preferentially targets human neuronal precursor cells (NPCs) in both monolayer and cortical brain organoid culture systems and stunts their growth. Although ZIKV is well recognized to cause microcephaly, there is no systematic analysis to demonstrate the effect of ZIKV on central nervous system (CNS) development, including brain malformations and spinal cord dysfunction. Here, we conducted a longitudinal analysis to show that a novel mouse model (infectedin uteroand monitored after birth until adulthood) recapitulates the effects of ZIKV infection affecting neural stem cells fate and leads to a thinner cortex and a smaller brain. Furthermore, we demonstrate the effect of ZIKV on spinal cord function. Specifically, we found significant reductions in neuron numbers in the anterior horn of grey matter of the spinal cord and muscle dystrophy with a significant decrease in forepaw grip strength in the ZIKV group. Thus, the established mouse model of ZIKV infection leading to abnormal CNS development will help to further advance our understanding of the disease pathogenesis.
Rational design, cognition and neuropathology evaluation of QTC-4-MeOBnE in a streptozotocin-induced mouse model of sporadic Alzheimer’s disease
Authors: Fronza Mariana G. , Baldinotti Rodolfo , Martins Maria Clara , Goldani Bruna , Dalberto Bianca Thaís , Kremer Frederico Schmitt , Begnini Karine , Pinto Luciano da Silva , Lenardão Eder João , Seixas Fabiana K. , Collares Tiago , Alves Diego , Savegnago Lucielli
Published: May 2019

Alzheimer’s disease (AD) is a multifactorial pathology characterized by amyloid deposits, neurofibrillary formation, oxidative stress and cholinergic system dysfunction. In this sense, here we report the rational design of a multi-target directed ligand (MTDL) for AD based on virtual screening and bioinformatic analyses, exploring the molecular targets β-secretase (BACE-1), glycogen synthase kinase-3β (GSK-3β) and acetylcholinesterase (AChE). After this screening, the compound with higher molecular docking affinity was selected, the 1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4 carboxamide(QTC-4-MeOBnE). To further our studies, the protective effect of QTC-4-MeOBnE (0.1 and 1 mg/kg for 20 days) on STZ-induced sporadic AD mice was determined. QTC-4-MeOBnE pretreatment attenuated cognitive and memory deficit induced by STZ in an object recognition test, Y-maze, social recognition test and step-down passive avoidance. The mechanisms underlying this action might be attributed to the reduction of lipid peroxidation and reactive species formation in the prefrontal cortex and hippocampus of mice submitted to STZ. In addition, QTC-4-MeOBnE pretreatment abolished the up-regulation of AChE activity and the overexpression ofGSK3β and genes involved in amyloid cascade such as BACE-1, protein precursor amyloid, у-secretase, induced by STZ. Moreover, toxicological parameters were not modified by QTC-4-MeOBnE chronic treatment. This evidence suggests that QTC-4-MeOBnE exerts its therapeutic effect through multiple pathways involved in AD.
Characterization and health risk assessment of PM2.5-bound polycyclic aromatic hydrocarbons in 5 urban cities of Zhejiang Province, China
Authors: Mo Zhe , Wang Zhifang , Mao Guangming , Pan Xuejiao , Wu Lizhi , Xu Peiwei , Chen Shuchang , Wang Aihong , Zhang Yongli , Luo Jinbin , Ye Xialiang , Wang Xiaofeng , Chen Zhijian , Lou Xiaoming
Published: May 2019

In 2015, we measured polycyclic aromatic hydrocarbons (PAHs) in atmospheric fine particulate matter (PM2.5) collected from 5 cities in Zhejiang Province. The mean toxic equivalent quotient (TEQ) values of benzo(a)pyrene (BaP) ranged between 1.2–3.1 ng/m3. The BaP-TEQ displayed seasonal trends, such that winter > spring and autumn > summer. During the winter, the most abundant individual PAHs were 4–6ring PAHs (84.04–91.65%). The median daily intake of atmospheric PAHs ranged between 2.0–7.4 ng/day for all populations, with seasonal trends identical to that of BaP-TEQ. The 95th incremental lifetime cancer risk (ILCR) values induced by PM2.5-bound PAHs were far lower than 10−6 for all populations. The data suggested that the pollution levels in the 5 Zhejiang Province cities were higher than the Chinese National Ambient Air Quality Standard (NAAQS). In the future, relevant measures should be taken to control atmospheric PAHs, especially 4–6 ring PAHs. The data also revealed no obvious cancer risk for populations residing in these 5 cities of Zhejiang Province.
Activation of Toll-like Receptor 2 (TLR2) induces Interleukin-6 trans-signaling
Authors: Flynn Charlotte M. , Garbers Yvonne , Lokau Juliane , Wesch Daniela , Schulte Dominik M. , Laudes Matthias , Lieb Wolfgang , Aparicio-Siegmund Samadhi , Garbers Christoph
Published: May 2019

Signaling of the pleiotropic cytokine Interleukin-6 (IL-6) via its soluble IL-6R (sIL-6R) has been termed trans-signaling and is thought to be responsible for the pro-inflammatory properties of IL-6. The sIL-6R can be generated by alternative mRNA splicing or proteolytic cleavage of the membrane-bound IL-6R. However, which stimuli induce sIL-6R release and which endogenous signaling pathways are required for this process is poorly understood. Here, we show that activation of Toll-like receptor 2 (TLR2) on primary human peripheral blood mononuclear cells (PBMCs) and on the monocytic cell line THP-1 induces expression and secretion of IL-6 and the generation of sIL-6R. We show by flow cytometry that monocytes are a PBMC subset that expresses TLR2 in conjunction with the IL-6R and are the major cellular source for both IL-6 and sIL-6R. Mechanistically, we find that the metalloproteases ADAM10 and ADAM17 are responsible for cleavage of the IL-6R and therefore sIL-6R generation. Finally, we identify the Extracellular-signal Regulated Kinase (ERK) cascade as a critical pathway that differentially regulates both IL-6 and sIL-6R generation in monocytes.
The activity of the saponin ginsenoside Rh2 is enhanced by the interaction with membrane sphingomyelin but depressed by cholesterol
Authors: Verstraeten Sandrine L. , Deleu Magali , Janikowska-Sagan Maria , Claereboudt Emily J. S. , Lins Laurence , Tyteca Donatienne , Mingeot-Leclercq Marie-Paule
Published: May 2019

The membrane activity of some saponins, such as digitonin or alpha-hederin, is usually attributed to their interaction with membrane cholesterol (Chol). This contrasts with our recent publication showing that Chol, contrary to sphingomyelin (SM), can delay the cytotoxicity of the saponin ginsenoside Rh2, challenging the usual view that most saponins mediate their membrane effects through interaction with Chol. The aim of the present study was to elucidate the respective importance of Chol and SM as compared to phosphatidylcholine (PC) species in the membrane-related effects of Rh2. On simple lipid monolayers, Rh2 interacted more favorably with eggSM and DOPC than with Chol and eggPC. Using Large Unilamellar Vesicles (LUVs) of binary or ternary lipid compositions, we showed that Rh2 increased vesicle size, decreased membrane fluidity and induced membrane permeability with the following preference: eggSM:eggPC > eggSM:eggPC:Chol > eggPC:Chol. On Giant Unilamellar Vesicles (GUVs), we evidenced that Rh2 generated positive curvatures in eggSM-containing GUVs and small buds followed by intra-luminal vesicles in eggSM-free GUVs. Altogether, our data indicate that eggSM promotes and accelerates membrane-related effects induced by Rh2 whereas Chol slows down and depresses these effects. This study reconsiders the theory that Chol is the only responsible for the activity of saponins.
Efficacy and safety of drug-eluting stenting compared with bypass grafting in diabetic patients with multivessel and/or left main coronary artery disease
Authors: Xin Xiaojun , Wang Xiangming , Dong Xuesi , Fan Yuanming , Shao Wei , Lu Xiang , Xiao Pingxi
Published: May 2019

Although percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) and bypass grafting are generally believed to be superior revascularization strategies in patients with coronary artery disease (CAD), the optimal strategy for diabetic patients is still controversial. This meta-analysis was performed to compare two methods of revascularization for patients with diabetes mellitus with left main coronary artery lesions or disease in multiple coronary arteries. Compared with the coronary artery bypass grafting (CABG) group, those receiving PCI-DES showed a greater risk of major adverse cardiovascular events (MACEs) (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.01–1.25, P = 0.03), major adverse cardiac and cerebrovascular events (MACCEs) (HR: 1.85, 95% CI: 1.58–2.16; P < 0.001), stroke (HR: 1.15, 95% CI: 1.02–1.29, P = 0.02), myocardial infarction (MI) (HR: 1.48, 95% CI: 1.04–2.09, P = 0.03), and repeat revascularization (HR: 3.23, 95% CI: 1.37–7.59, P = 0.007). CABG for diabetic patients with multivessel and/or left main CAD was superior to PCI-DES with regard to MACEs, MACCEs, MI, repeat revascularization and stroke, but there was no clear difference in all-cause mortality.
Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus
Authors: Cordero Esteban M. , Cortez Cristian , Yoshida Nobuko , da Silveira José Franco
Published: May 2019

Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.T.cruziGPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP). Transfection ofT.cruziepimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82. Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion. Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP. Deletion of SP generated a ~72 kDa protein devoid ofN-linked oligosaccharides allowing irrefutable identification of GP82 precursor. SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association. Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus. This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
Matrix stiffness modulates the activity of MMP-9 and TIMP-1 in hepatic stellate cells to perpetuate fibrosis
Authors: Lachowski Dariusz , Cortes Ernesto , Rice Alistair , Pinato David , Rombouts Krista , del Rio Hernandez Armando
Published: May 2019

Liver fibrosis is characterised by a dense and highly cross-linked extracellular matrix (ECM) which promotes progression of diseases such as hepatocellular carcinoma. The fibrotic microenvironment is characterised by an increased stiffness, with rigidity associated with disease progression. External stiffness is known to promote hepatic stellate cell (HSC) activation through mechanotransduction, leading to increased secretion of ECM components. HSCs are key effector cells which maintain the composition of the ECM in health and disease, not only by regulating secretion of ECM proteins such as collagen, but also ECM-degrading enzymes called matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Uninhibited MMPs degrade ECM proteins to reduce external rigidity. Using fibronectin-coated polyacrylamide gels to alter substrate rigidity without altering ligand density, we show that fibrotic rigidities downregulate MMP-9 expression and secretion, and also upregulate secretion of TIMP-1, though not its expression. Using tissue immunofluorescence studies, we also report that the expression of MMP-9 is significantly decreased in activated HSCs in fibrotic tissues associated with hepatocellular carcinoma. This suggests the presence of a mechanical network that allows HSCs to maintain a fibrotic ECM, with external rigidity providing feedback which affects MMP-9 and TIMP-1 secretion, which may become dysregulated in fibrosis.
The Effect of Iranian Propolis on Glucose Metabolism, Lipid Profile, Insulin Resistance, Renal Function and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Clinical Trial
Authors: Zakerkish Mehrnoosh , Jenabi Maryam , Zaeemzadeh Narjes , Hemmati Ali Asghar , Neisi Niloofar
Published: May 2019

Propolis is a natural product with many biological properties including hypoglycemic activity and modulating lipid profile. The present study was designed to evaluate the effect of Iranian propolis extract on glucose metabolism, Lipid profile, Insulin resistance, renal and liver function as well as inflammatory biomarkers in patients with type 2 diabetes mellitus (T2DM). A double-blind, placebo-controlled clinical trial was conducted. The duration of the study lasted 90 days. Patients with T2DM were recruited and randomly divided into an Iranian propolis group (1000 mg/day) (n = 50) and a placebo group (n = 44). There was a significant decrease in the serum levels of glycosylated hemoglobin (HbA1c), 2-hour post prandial (2hpp), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), High sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α). However, there was a notable elevation in the serum HDL-C in the propolis group compared with the placebo group. In addition, a notable reduction in serum liver transaminase (ALT and AST) and blood urea nitrogen (BUN) concentrations in the propolis group was observed. Iranian propolis has beneficial effects on reducing post prandial blood glucose, serum insulin, insulin resistance, and inflammatory cytokines. It is also a useful treatment for preventing the liver and renal dysfunction, as well as, elevating HDL-C concentrations in patients with T2DM.