bluuebunny/crossref_metadata_2025_split huggingface dataset:
VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
Authors: Díaz-Alonso Javier , Paraíso-Luna Juan , Navarrete Carmen , del Río Carmen , Cantarero Irene , Palomares Belén , Aguareles José , Fernández-Ruiz Javier , Bellido María Luz , Pollastro Federica , Appendino Giovanni , Calzado Marco A. , Galve-Roperh Ismael , Muñoz Eduardo 
Published: July 2016

AbstractCannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ. We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity. This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells. The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32+ neuronal loss in these Huntington’s-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain. These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington’s disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.
Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance
Authors: Frise Rebecca , Bradley Konrad , van Doremalen Neeltje , Galiano Monica , Elderfield Ruth A. , Stilwell Peter , Ashcroft Jonathan W. , Fernandez-Alonso Mirian , Miah Shahjahan , Lackenby Angie , Roberts Kim L. , Donnelly Christl A. , Barclay Wendy S. 
Published: July 2016

AbstractInfluenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution.
Novel technique to suppress hydrocarbon contamination for high accuracy determination of carbon content in steel by FE-EPMA
Authors: Yamashita Takako , Tanaka Yuji , Nagoshi Masayasu , Ishida Kiyohito 
Published: July 2016

AbstractIn multiphase steels, control of the carbon contents in the respective phases is the most important factor in alloy design for achieving high strength and high ductility. However, it is unusually difficult to determine the carbon contents in multiphase structures with high accuracy by electron probe microanalysis (EPMA) due to the unavoidable effect of hydrocarbon contamination during measurements. We have investigated new methods for suppressing hydrocarbon contamination during field emission (FE) EPMA measurements as well as a conventional liquid nitrogen trap. Plasma cleaner inside the specimen chamber results in a improvement of carbon-content determination by point analysis, increasing precision tenfold from the previous 0.1 mass%C to 0.01 mass%C. Stage heating at about 100 °C dramatically suppresses contamination growth during continuous point measurement and mapping. By the combination of above two techniques, we successfully visualized the two-dimensional carbon distribution in a dual-phase steel. It was also noted that the carbon concentrations at the ferrite/martensite interfaces were not the same across all interfaces, and local variation was observed. The developed technique is expected to be a powerful tool for understanding the mechanisms of mechanical properties and microstructural evolution, thereby contributing to the design of new steel products with superior properties.
Development of a Biomimetic Chondroitin Sulfate-modified Hydrogel to Enhance the Metastasis of Tumor Cells
Authors: Liu Yang , Wang Shujun , Sun Dongsheng , Liu Yongdong , Liu Yang , Wang Yang , Liu Chang , Wu Hao , Lv Yan , Ren Ying , Guo Xin , Sun Guangwei , Ma Xiaojun 
Published: July 2016

AbstractTumor metastasis with resistance to anticancer therapies is the main cause of death in cancer patients. It is necessary to develop reliable tumor metastasis models that can closely recapitulate the pathophysiological features of the native tumor tissue. In this study, chondroitin sulfate (CS)-modified alginate hydrogel beads (ALG-CS) are developed to mimic the in vivo tumor microenvironment with an abnormally increased expression of CS for the promotion of tumor cell metastasis. The modification mechanism of CS on alginate hydrogel is due to the cross-linking between CS and alginate molecules via coordination of calcium ions, which enables ALG-CS to possess significantly different physical characteristics than the traditional alginate beads (ALG). And quantum chemistry calculations show that in addition to the traditional egg-box structure, novel asymmetric egg-box-like structures based on the interaction between these two kinds of polymers are also formed within ALG-CS. Moreover, tumor cell metastasis is significantly enhanced in ALG-CS compared with that in ALG, as confirmed by the increased expression of MMP genes and proteins and greater in vitro invasion ability. Therefore, ALG-CS could be a convenient and effective 3D biomimetic scaffold that would be used to construct standardized tumor metastasis models for tumor research and anticancer drug screening.
Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation
Authors: Carthy Jon M. , Stöter Martin , Bellomo Claudia , Vanlandewijck Michael , Heldin Angelos , Morén Anita , Kardassis Dimitris , Gahman Timothy C. , Shiau Andrew K. , Bickle Marc , Zerial Marino , Heldin Carl-Henrik , Moustakas Aristidis 
Published: July 2016

AbstractPlasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition. In addition to TGF-β receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked α-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-β-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-β-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer.
Interleukin-1β, lipocalin 2 and nitric oxide synthase 2 are mechano-responsive mediators of mouse and human endothelial cell-osteoblast crosstalk
Authors: Veeriah Vimal , Zanniti Angelo , Paone Riccardo , Chatterjee Suvro , Rucci Nadia , Teti Anna , Capulli Mattia 
Published: July 2016

AbstractEndothelial cells are spatially close to osteoblasts and regulate osteogenesis. Moreover, they are sensitive to mechanical stimuli, therefore we hypothesized that they are implicated in the regulation of bone metabolism during unloading. Conditioned media from endothelial cells (EC-CM) subjected to simulated microgravity (0.08gand 0.008g) increased osteoblast proliferation and decreased their differentiation compared to unit gravity (1g) EC-CM. Microgravity-EC-CM increased the expression of osteoblastRankland subsequent osteoclastogenesis and induced the osteoblast de-differentiating factor, Lipocalin 2 (Lcn2), whose downregulation recovered osteoblast activity, decreasedRanklexpression and reduced osteoclastogenesis. Microgravity-EC-CM enhanced osteoblastNO-Synthase2 (NOS2) andCycloOXygenase2 (COX2) expression. Inhibition of NOS2 or NO signaling reduced osteoblast proliferation and rescued their differentiation. Nuclear translocation of the Lcn2/NOS2 transcription factor, NF-κB, occurred in microgravity-EC-CM-treated osteoblasts and in microgravity-treated endothelial cells, alongside high expression of the NF-κB activator, IL-1β. IL-1β depletion and NF-κB inhibition reduced osteoblast proliferation and rescued differentiation.Lcn2andNOS2were incremented inex vivocalvarias cultured in microgravity-EC-CM andin vivotibias and calvarias injected with microgravity-EC-CM. Furthermore, tibias of botulin A toxin-treated and tail-suspended mice, which featured unloading and decreased bone mass, showed higher expression ofIL-1β, Lcn2andNos2, suggesting their pathophysiologic involvement in endothelial cell-osteoblast crosstalk.
Novel avian influenza A (H5N6) viruses isolated in migratory waterfowl before the first human case reported in China, 2014
Authors: Bi Yuhai , Liu Haizhou , Xiong Chaochao , Di Liu  , Shi Weifeng , Li Mingxin , Liu Siling , Chen Jing , Chen Guang , Li Yong , Yang Guoxiang , Lei Yongsong , Xiong Yanping , Lei Fumin , Wang Hanzhong , Chen Quanjiao , Chen Jianjun , Gao George F. 
Published: July 2016

AbstractIn May 2014, China formally confirmed the first human infection with the novel H5N6 avian influenza virus (AIV) in Sichuan Province. Before the first human case was reported, surveillance of AIVs in wild birds resulted in the detection of three H5N6 viruses in faecal samples from migratory waterfowl in Chenhu wetlands, Hubei Province, China. Genetic and phylogenetic analyses revealed that these three novel viruses were closely related to the H5N6 virus that has caused human infections in China since 2014. A Bayesian phylogenetic reconstruction of all eight segments suggests multiple reassortment events in the evolution of these viruses. The hemagglutinin (HA) and neuraminidase (NA) originated from the H5N2 and H6N6 AIVs, respectively, whereas all six internal genes were derived from avian H5N1 viruses. The reassortant may have occurred in eastern China during 2012–2013. A phylogeographic analysis of the HA and NA genes traced the viruses to southern China, from where they spread to other areas via eastern China. A receptor-binding test showed that H5N6 viruses from migratory waterfowl had human-type receptor-binding activity, suggesting a potential for transmission to humans. These data suggest that migratory waterfowl may play a role in the dissemination of novel H5N6 viruses.
Floating photocatalyst of B–N–TiO2/expanded perlite: a sol–gel synthesis with optimized mesoporous and high photocatalytic activity
Authors: Xue Hongbo , Jiang Ya , Yuan Kechun , Yang Tingting , Hou Jianhua , Cao Chuanbao , Feng Ke , Wang Xiaozhi 
Published: July 2016

AbstractOptimized mesoporous photocatalyst endowed with high specific surface area and large pore size was synthesized by sol–gel method. These large pore mesoporous materials (33.39 nm) were conducive to the movement of larger molecules or groups in pore path and for effective use of active sites. The high specific surface area (SBET, 99.23 m2 g−1) was beneficial to catalytic oxidation on the surface. Moreover, B and N co-doped anatase TiO2 in the presence of Ti–O–B–N and O–Ti–B–N contributed to the pore structure optimization and enhanced photoresponse capacity with a narrow band gap and red shift of absorption. The obtained materials with floating characteristics based on expanded perlite (EP) showed favorable features for photocatalytic activity. The best RhB photodegration rate of B–N–TiO2/EP (6 mg/g, 24 wt% TiO2) reached 99.1% after 5 h in the visible region and 99.8% after 1 h in the UV region. The findings can provide insights to obtain floatable photocatalysts with simple preparation method, optimized mesoporous, co-doping agents, as well as good photocatalytic performance, coverable and reusability. B–N–TiO2/EP has potential applications for practical environmental purification.
Altered responsiveness of BNST and amygdala neurons in trauma-induced anxiety
Authors: Rodríguez-Sierra O E , Goswami S , Turesson H K , Pare D 
Published: July 2016

AbstractA highly conserved network of brain structures regulates the expression of fear and anxiety in mammals. Many of these structures display abnormal activity levels in post-traumatic stress disorder (PTSD). However, some of them, like the bed nucleus of the stria terminalis (BNST) and amygdala, are comprised of several small sub-regions or nuclei that cannot be resolved with human neuroimaging techniques. Therefore, we used a well-characterized rat model of PTSD to compare neuronal properties in resilient vs PTSD-like rats using patch recordings obtained from different BNST and amygdala regions in vitro. In this model, a persistent state of extreme anxiety is induced in a subset of susceptible rats following predatory threat. Previous animal studies have revealed that the central amygdala (CeA) and BNST are differentially involved in the genesis of fear and anxiety-like states, respectively. Consistent with these earlier findings, we found that between resilient and PTSD-like rats were marked differences in the synaptic responsiveness of neurons in different sectors of BNST and CeA, but whose polarity was region specific. In light of prior data about the role of these regions, our results suggest that control of fear/anxiety expression is altered in PTSD-like rats such that the influence of CeA is minimized whereas that of BNST is enhanced. A model of the amygdalo-BNST interactions supporting the PTSD-like state is proposed.
Proposal of compensation for intra‐ and inter‐channel nonlinear distortions using optical compensation and nonlinear equalisation
Authors: Kawahara H. , Yamamoto S. , Fukutoku M. 
Published: July 2016

A novel transmission system that adaptively compensates for intra‐ and inter‐channel nonlinear distortions while alleviating the computation load is described. It does so by using an optical dispersion compensation at optical nodes and a Volterra‐based multi‐channel nonlinear equalisation. Simulation results show that 3.8 dB Q‐factor improvements are obtained against conventional systems that do not compensate for nonlinear distortions.
Die komplizierte Gicht
Authors: Illgner U. , Maier A. , Bause L. , Seintsch H. 
Published: July 2016

ZusammenfassungEin 57-jähriger Patient wurde aus der internistischen Abteilung einer auswärtigen Klinik übernommen, mit zahlreichen Gichttophi und einer Überwärmung des rechten Knies und des rechten Ellenbogens. Seit 20 Tagen bestand eine probatorische parenterale Antibiotikatherapie. Durch eine sofortige Punktion des rechten Kniegelenks konnte die Diagnose einer bakteriellen Arthritis gestellt werden. Es erfolgte umgehend eine Operation mit Spülung und ausführlichem Debridement unter der Weiterführung der Antibiotikatherapie. Bei Patienten mit Gicht und Verdacht auf eine zusätzliche Infektion muss immer eine vollständige und konsequente Fokussuche und ggf. eine operative Focussanierung durchgeführt werden.
Hierarchical decision processes that operate over distinct timescales underlie choice and changes in strategy
Authors: Purcell Braden A. , Kiani Roozbeh 
Published: July 2016

Significance
Decisions are guided by available information and strategies that link information to action. Following a bad outcome, two potential sources of error—flawed strategy and poor information—must be distinguished to improve future performance. In a direction discrimination task where subjects decide by accumulating sensory evidence to a bound, we show that humans disambiguate sources of error by integrating expected accuracy and outcome over multiple choices. The strategy switches when the integral reaches a threshold. A hierarchy of decision processes in which lower levels integrate sensory evidence over short timescales, and higher levels interact with lower levels over longer timescales, quantitatively explains the behavior. Expected accuracy links these two levels and enables adaptive changes of decision strategy.
Graptolite community responses to global climate change and the Late Ordovician mass extinction
Authors: Sheets H. David , Mitchell Charles E. , Melchin Michael J. , Loxton Jason , Štorch Petr , Carlucci Kristi L. , Hawkins Andrew D. 
Published: July 2016

Significance
Climate change during Late Ordovician mass extinction drove an ecologically selective decline in the abundance of deep-water macrozooplankton, accompanied by a shift to simpler, less even communities. These results indicate that the species abundance structure of planktic communities may be a leading indicator of the effects of climate change on biodiversity and a more sensitive gauge of those effects than taxonomic diversity change alone. Additionally, we present a Bayesian likelihood method of habitat inference that may be applicable to other similar cases.
Model confirmation in climate economics
Authors: Millner Antony , McDermott Thomas K. J. 
Published: July 2016

Significance
Benefit–cost integrated assessment models (BC-IAMs) combine climate science, impacts studies, and representations of long-run economic growth to estimate the costs and benefits of climate policy. They provide valuable qualitative insights into how policy outcomes might depend on ethical and empirical assumptions. Increasingly, however, BC-IAMs are being used to inform quantitative policy choices, despite their economic components being largely untested, or untestable, over relevant time scales. We demonstrate the potential benefits of model confirmation exercises for policy applications, demonstrating that the economic growth model used by a prominent BC-IAM had little predictive power over the 20th century. Insofar as possible, out-of-sample empirical tests of the economic components of BC-IAMs should inform their future development for real-world applications.
Growth mindset tempers the effects of poverty on academic achievement
Authors: Claro Susana , Paunesku David , Dweck Carol S. 
Published: July 2016

Significance
This study is the first, to our knowledge, to show that a growth mindset (the belief that intelligence is not fixed and can be developed) reliably predicts achievement across a national sample of students, including virtually all of the schools and socioeconomic strata in Chile. It also explores the relationship between income and mindset for the first time, to our knowledge, finding that students from lower-income families were less likely to hold a growth mindset than their wealthier peers but that those who did hold a growth mindset were appreciably buffered against the deleterious effects of poverty on achievement. These results suggest that mindsets may be one mechanism through which economic disadvantage can affect achievement.
Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy
Authors: Imamichi Hiromi , Dewar Robin L. , Adelsberger Joseph W. , Rehm Catherine A. , O’Doherty Una , Paxinos Ellen E. , Fauci Anthony S. , Lane H. Clifford 
Published: July 2016

Significance
The presence of “defective” HIV-1 proviruses in HIV-infected patients has been well documented. The current consensus view of the “defective” proviruses is that these are dead-end products that do not give rise to progeny virus and thus collectively represent a “graveyard” of viruses. We describe the presence of defective HIV-1 proviruses capable of transcribing novel unspliced HIV-RNA species in HIV-infected patients on combination antiretroviral therapy. We propose that the proviruses persistently present in combination antiretroviral therapy-treated patients are not defective in a conventional sense, but rather represent incomplete forms of proviruses encoding translationally competent HIV-RNA transcripts. Strategies directed toward curing HIV-1 infection and eliminating the state of persistent immune activation need to include approaches designed to eliminate cells harboring such proviruses.
Rates and Effects of Branding due to Electroshock Observed in Southern California Steelhead in Topanga Creek, California
Authors: Dagit Rosi , Krug Jenna 
Published: July 2016

Abstract
As part of a 7-year lifecycle monitoring study, electroshocking was used to capture and characterize a small population of federally listed endangered southern California steelhead Oncorhynchus mykiss in Topanga Creek, Los Angeles, California. Electroshocking is a tool widely used to study fish populations, despite its potential behavioral and physical effects on individuals. We examined rates of external hemorrhaging (i.e., branding) and its effect on growth rates and survival of recaptured individuals. Rates of branding were low (0–3%) during most November events from 2008 to 2014, but higher during all March events (8–23%) and during the November 2011 event (13%). Overall, 5% of the total captured individuals exhibited branding. Growth rates (mm/d) of individuals recaptured after branding were not significantly different, but on average were 9% lower than average daily growth rates for individuals in the same size-class captured and recaptured in the same time periods. In general, larger fish were more likely to be branded than were smaller fish (P &lt; 0.0001). Although 69% of brandings occurred in pool habitats, which tend to be larger and deeper than other habitats, branding was not significantly more likely to occur in any habitat type (P = 0.13) or in any substrate type (P = 0.16), and mean or maximum depth of habitat was not related to the rate of branding. The population-level effects associated with branding remain unclear. Although important information has been obtained through the use of electroshocking, the cumulative effects of electroshocking-induced injuries to this endangered species need to be considered.
Received March 2, 2015; accepted March 27, 2016 Published online July 19, 2016