bluuebunny/crossref_metadata_2025 huggingface dataset:
Simuliertes Glücksspiel im Internet
Authors: Hayer Tobias , Rosenkranz Moritz , Meyer Gerhard , Brosowski Tim
Published: February 2019

Zusammenfassung. Die vorliegende Studie beschäftigt sich mit simulierten Internet-Glücksspielen und folglich mit neuartigen Spielangeboten, die an der Schnittstelle von Computer- und Glücksspielen anzusiedeln sind. Erstmals werden für Deutschland in diesem Zusammenhang differenzierte Daten zum Nachfrageverhalten sowie zu teilnahmefördernden Bedingungen vorgelegt. Grundlage der Datenanalyse ist eine quantitative Erhebung mit N = 1 905 Schülern und Schülerinnen der Klassenstufen 6 bis 10 ( M = 13.8 Jahre) aus drei norddeutschen Großstädten. Die Ergebnisse zeigen, dass etwa die Hälfte aller Befragten in den letzten 12 Monaten am simulierten Internet-Glücksspiel teilgenommen hat. Dabei dominieren Spielerfahrungen innerhalb von Videospielen. Darüber hinaus variieren die Prädiktoren einer Spielteilnahme in Abhängigkeit konkreter Spielvarianten (innerhalb von Videospielen, über Apps, in sozialen Netzwerken, als Demospiele). Abschließend werden weiterführende Handlungsbedarfe in Bezug auf Prävention, Regulation und Forschung diskutiert.
Differenzielle Analysen zum Zusammenhang zwischen Kreativität und ADHS bei Kindern und Jugendlichen
Authors: Lüdeke Sören , Linderkamp Friedrich , Cevani Isabelle
Published: February 2019

Zusammenfassung. Befunde zur Kreativität bei Kindern und Jugendlichen mit ADHS sind widersprüchlich. Zur Erfassung von Kreativität wird oft auf quantitative Leistungsmaße wie divergentes Denken in Speed-Tests zurückgegriffen anstelle von qualitativen Aspekten wie Unkonventionalität und Humor. Diese Studie untersucht, ob sich Kinder und Jugendliche mit ADHS hinsichtlich quantitativer und qualitativer Kreativitätsmerkmale von einer Kontrollgruppe unterscheiden. Die Stichprobe schließt N = 71 Kinder und Jugendliche (10 – 14 Jahre) ein, davon 17 mit klinischer ADHS-Diagnose und 16 mit ADHS-Symptomen gemäß DISYPS-II. In einem standardisierten Kreativitätstest erreichen die ADHS-Gruppen unabhängig von Alter und Geschlecht signifikant bessere Gesamtleistungen als die Kontrollgruppe. Unterschiede bestehen vor allem in den Bereichen Humor und emotionale Expressivität zeichnerischer Darstellungen. Die Ergebnisse unterstreichen die Bedeutung ressourcenorientierter Perspektiven auf Kinder und Jugendliche mit ADHS.
Deformation, Annealing, Melt‐Rock Interaction, and Seismic Properties of an Old Domain of the Equatorial Atlantic Lithospheric Mantle
Authors: Liu Shiran , Tommasi Andréa , Vauchez Alain , Mazzucchelli Maurizio
Published: February 2019

We analyzed a set of mantle xenoliths from the Fernando de Noronha archipelago to constrain the roles of deformation, cooling, annealing, and melt percolation in the evolution of the mantle lithosphere of the equatorial Atlantic. The peridotites are dominantly lherzolites with coarse granular or porphyroclastic microstructures. Equilibrium temperatures range between 850 and 1,000 °C. Olivine crystal preferred orientations (CPO) have mainly orthorhombic patterns characterized by clear [100] and [010] point maxima or a fiber‐[100] tendency; these patterns imply deformation by dislocation creep with dominant activation of the [100](010) slip system. Olivine fiber‐[010] patterns are less common; they probably result from recrystallization or melt‐rock interaction. Annealing after deformation partially recovered the microstructures and reduced the olivine CPO strength. Pyroxene CPOs often have weak consistency with olivine CPO, implying post‐deformation refertilization. Chemical compositions are systematically more fertile than those from abyssal peridotites from the Mid‐Atlantic Ridge. These compositions together with the microstructures suggest two stages of melt‐rock interaction. An early refertilization of the base of the lithosphere due to continuous percolation of small melt fractions and later, more important, but local chemical changes (both refertilization and dunitization) as well as recrystallization due to reactive melt percolation likely associated with the Cenozoic volcanism. By comparing the calculated seismic properties with existing seismological data we argue that the moderate seismic anisotropy displayed by the Fernando de Noronha mantle xenoliths likely records past horizontal asthenospheric flow parallel to the spreading direction frozen in the lithospheric mantle as the plate cooled.
The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the International Myeloma Working Group (IMWG)
Authors: Kyriakou Charalampia , Molloy Sean , Vrionis Frank , Alberico Ronald , Bastian Leonard , Zonder Jeffrey A. , Giralt Sergio , Raje Noopur , Kyle Robert A. , Roodman David G. D. , Dimopoulos Meletios A. , Rajkumar S. Vincent , Durie Brian B. G. , Terpos Evangelos
Published: February 2019

Multiple myeloma (MM) represents approximately 15% of haematological malignancies and most of the patients present with bone involvement. Focal or diffuse spinal osteolysis may result in significant morbidity by causing painful progressive vertebral compression fractures (VCFs) and deformities. Advances in the systemic treatment of myeloma have achieved high response rates and prolonged the survival significantly. Early diagnosis and management of skeletal events contribute to improving the prognosis and quality of life of MM patients. The management of patients with significant pain due to VCFs in the acute phase is not standardised. While some patients are successfully treated conservatively, and pain relief is achieved within a few weeks, a large percentage has disabling pain and morbidity and hence they are considered for surgical intervention. Balloon kyphoplasty and percutaneous vertebroplasty are minimally invasive procedures which have been shown to relieve pain and restore function. Despite increasing positive evidence for the use of these procedures, the indications, timing, efficacy, safety and their role in the treatment algorithm of myeloma spinal disease are yet to be elucidated. This paper reports an update of the consensus statement from the International Myeloma Working Group on the role of cement augmentation in myeloma patients with VCFs.
Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment
Authors: Guillon Jordan , Petit Coralie , Moreau Marie , Toutain Bertrand , Henry Cécile , Roché Henry , Bonichon-Lamichhane Nathalie , Salmon Jean Paul , Lemonnier Jérôme , Campone Mario , Verrièle Véronique , Lelièvre Eric , Guette Catherine , Coqueret Olivier
Published: February 2019

Senescence is a tumor-suppressive mechanism induced by telomere shortening, oncogenes, or chemotherapy treatment. Although it is clear that this suppressive pathway leads to a permanent arrest in primary cells, this might not be the case in cancer cells that have inactivated their suppressive pathways. We have recently shown that subpopulations of cells can escape chemotherapy-mediated senescence and emerge as more transformed cells that induce tumor formation, resist anoikis, and are more invasive. In this study, we characterized this emergence and showed that senescent cells favor tumor growth and metastasis, in vitro and in vivo. Senescence escape was regulated by secreted proteins produced during emergence. Among these, we identified thrombospondin-1 (TSP1), a protein produced by senescent cells that prevented senescence escape. Using SWATH quantitative proteomic analysis, we found that TSP1 can be detected in the serum of patients suffering from triple-negative breast cancer and that its low expression was associated with treatment failure. The results also indicate that senescence escape is explained by the emergence of CD47low cells that express a reduced level of CD47, the TSP1 receptor. The results show that CD47 expression is regulated by p21waf1. The cell cycle inhibitor was sufficient to maintain senescence since its downregulation in senescent cells increased cell emergence. This leads to the upregulation of Myc, which then binds to the CD47 promoter to repress its expression, allowing the generation of CD47low cells that escape the suppressive arrest. Altogether, these results uncovered a new function for TSP1 and CD47 in the control of chemotherapy-mediated senescence.
Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway
Authors: Yang Wei , Wu Peng-fei , Ma Jian-xing , Liao Mao-jun , Wang Xu-hui , Xu Lun-shan , Xu Min-hui , Yi Liang
Published: February 2019

High aggressiveness is a hallmark of glioblastoma and predicts poor prognosis of patients with glioblastoma. The expression level of sortilin has been preliminarily reported to be elevated in high-grade glioma; however, the potential significance of sortilin in glioblastoma progression has not been elucidated. In this study, we investigated the oncogenic effect of sortilin in glioblastoma. Increased levels of sortilin were noted in the mesenchymal subtype of glioblastoma and highly aggressive subtypes of glioblastoma tissues and cell lines. In addition, high levels of sortilin predicted poor prognoses in patients with glioblastoma. Sortilin knockdown or inhibition with AF38469 (an orally bioavailable inhibitor of sortilin) significantly suppressed migration and invasion by inhibiting EMT-like mesenchymal transition in glioblastoma cells. Furthermore, we proved that sortilin promoted cell invasion mainly via Glycogen synthase kinase 3 beta (GSK-3β)/β-catenin/Twist-induced EMT-like mesenchymal transition in glioblastoma. Taken together, our results demonstrate a critical role of sortilin in glioblastoma invasion and EMT-like mesenchymal transition, indicating that sortilin contributes to glioblastoma progression. These data also highlight the dramatic antitumor effects of AF38469 in glioblastoma, suggesting that AF38469 is a potentially powerful antitumor agent for sortilin-overexpressing human glioblastoma.
PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation
Authors: Tong Lei , Wang Long , Yao Shuangshuang , Jin Lina , Yang Jian , Zhang Yifei , Ning Guang , Zhang Zhiguo
Published: February 2019

Peroxisome proliferator-activated receptor δ (PPARδ) belongs to the nuclear receptor family and is involved in metabolic diseases. Although PPARδ is known to attenuate hepatic lipid deposition, its mechanism remains unclear. Here, we show that PPARδ is a potent stimulator of hepatic autophagic flux. The expression levels of PPARδ and autophagy-related proteins were decreased in liver tissues from obese and ageing mice. Pharmacological and adenovirus-mediated increases in PPARδ expression and activity were achieved in obese transgenic db/db and high fat diet-fed mice. Using genetic, pharmacological and metabolic approaches, we demonstrate that PPARδ reduces intrahepatic lipid content and stimulates β-oxidation in liver and hepatic cells by an autophagy–lysosomal pathway involving AMPK/mTOR signalling. These results provide novel insight into the lipolytic actions of PPARδ through autophagy in the liver and highlight its potential beneficial effects in NAFLD.
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
Authors: Hess Daniel L. , Kelly-Goss Molly R. , Cherepanova Olga A. , Nguyen Anh T. , Baylis Richard A. , Tkachenko Svyatoslav , Annex Brian H. , Peirce Shayn M. , Owens Gary K.
Published: February 2019

The stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of Oct4 that Oct4 regulates perivascular cell migration and recruitment during angiogenesis. Knockout of Oct4 in perivascular cells significantly impairs perivascular cell migration, increases perivascular cell death, delays endothelial cell migration, and promotes vascular leakage following corneal angiogenic stimulus. Knockout of Oct4 in perivascular cells also impairs perfusion recovery and decreases angiogenesis following hindlimb ischemia. Transcriptomic analyses demonstrate that expression of the migratory gene Slit3 is reduced following loss of Oct4 in cultured SMCs, and in Oct4-deficient perivascular cells in ischemic hindlimb muscle. Together, these results provide evidence that Oct4 plays an essential role within perivascular cells in injury- and hypoxia-induced angiogenesis.
Viral pathogens hitchhike with insect sperm for paternal transmission
Authors: Mao Qianzhuo , Wu Wei , Liao Zhenfeng , Li Jiajia , Jia Dongsheng , Zhang Xiaofeng , Chen Qian , Chen Hongyan , Wei Jing , Wei Taiyun
Published: February 2019

Arthropod-borne viruses (arboviruses) can be maternally transmitted by female insects to their offspring, however, it is unknown whether male sperm can directly interact with the arbovirus and mediate its paternal transmission. Here we report that an important rice arbovirus is paternally transmitted by the male leafhoppers by hitchhiking with the sperm. The virus-sperm binding is mediated by the interaction of viral capsid protein and heparan sulfate proteoglycan on the sperm head surfaces. Mating experiments reveal that paternal virus transmission is more efficient than maternal transmission. Such paternal virus transmission scarcely affects the fitness of adult males or their offspring, and plays a pivotal role in maintenance of viral population during seasons unfavorable for rice hosts in the field. Our findings reveal that a preferred mode of vertical arbovirus transmission has been evolved by hitchhiking with insect sperm without disturbing sperm functioning, facilitating the long-term viral epidemic and persistence in nature.
Man-made microbial resistances in built environments
Authors: Mahnert Alexander , Moissl-Eichinger Christine , Zojer Markus , Bogumil David , Mizrahi Itzhak , Rattei Thomas , Martinez José Luis , Berg Gabriele
Published: February 2019

Antimicrobial resistance is a serious threat to global public health, but little is known about the effects of microbial control on the microbiota and its associated resistome. Here we compare the microbiota present on surfaces of clinical settings with other built environments. Using state-of-the-art metagenomics approaches and genome and plasmid reconstruction, we show that increased confinement and cleaning is associated with a loss of microbial diversity and a shift from Gram-positive bacteria, such as Actinobacteria and Firmicutes, to Gram-negative such as Proteobacteria. Moreover, the microbiome of highly maintained built environments has a different resistome when compared to other built environments, as well as a higher diversity in resistance genes. Our results highlight that the loss of microbial diversity correlates with an increase in resistance, and the need for implementing strategies to restore bacterial diversity in certain built environments.
A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT
Authors: Talavera Ariel , Tamman Hedvig , Ainelo Andres , Konijnenberg Albert , Hadži San , Sobott Frank , Garcia-Pino Abel , Hõrak Rita , Loris Remy
Published: February 2019

Bacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. A typical regulatory strategy involves the antitoxin binding and repressing its own promoter while the toxin often acts as a co-repressor. Here we show that Pseudomonas putida graTA-encoded antitoxin GraA and toxin GraT differ from other TA proteins in the sense that not the antitoxin but the toxin possesses a flexible region. GraA auto-represses the graTA promoter: two GraA dimers bind cooperatively at opposite sides of the operator sequence. Contrary to other TA modules, GraT is a de-repressor of the graTA promoter as its N-terminal disordered segment prevents the binding of the GraT2A2 complex to the operator. Removal of this region restores operator binding and abrogates Gr aT toxicity. GraTA represents a TA module where a flexible region in the toxin rather than in the antitoxin controls operon expression and toxin activity.
Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes
Authors: Subramanian Vijayalakshmi V. , Zhu Xuan , Markowitz Tovah E. , Vale-Silva Luis A. , San-Segundo Pedro A. , Hollingsworth Nancy M. , Keeney Scott , Hochwagen Andreas
Published: February 2019

Faithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 kb near all telomeres that escape DSB down-regulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes.
Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells
Authors: Cheng Min , Yang Junjie , Zhao Xiaoqi , Zhang Eric , Zeng Qiutang , Yu Yang , Yang Liu , Wu Bangwei , Yi Guiwen , Mao Xiaobo , Huang Kai , Dong Nianguo , Xie Min , Limdi Nita A. , Prabhu Sumanth D. , Zhang Jianyi , Qin Gangjian
Published: February 2019

Myocardial microRNAs (myo-miRs) are released into the circulation after acute myocardial infarction (AMI). How they impact remote organs is however largely unknown. Here we show that circulating myo-miRs are carried in exosomes and mediate functional crosstalk between the ischemic heart and the bone marrow (BM). In mice, we find that AMI is accompanied by an increase in circulating levels of myo-miRs, with miR-1, 208, and 499 predominantly in circulating exosomes and miR-133 in the non-exosomal component. Myo-miRs are imported selectively to peripheral organs and preferentially to the BM. Exosomes mediate the transfer of myo-miRs to BM mononuclear cells (MNCs), where myo-miRs downregulate CXCR4 expression. Injection of exosomes isolated from AMI mice into wild-type mice downregulates CXCR4 expression in BM-MNCs and increases the number of circulating progenitor cells. Thus, we propose that myo-miRs carried in circulating exosomes allow a systemic response to cardiac injury that may be leveraged for cardiac repair.
Prospects for low-toxicity lead-free perovskite solar cells
Authors: Ke Weijun , Kanatzidis Mercouri G.
Published: February 2019

Since the 2012 breakthroughs1–3, it is now very much accepted that halide perovskite solar cells may have a strong practical impact in next-generation solar cells. The most efficient solar cells are using Pb-based halide perovskites. The presence of Pb in these devices, however, has caused some concerns due to the high perceived toxicity of Pb, which may slow down or even hinder the pace of commercialization. Therefore, the science community has been searching for lower-toxicity perovskite-type materials as a back-up strategy. The community is paying significant attention to Pb-free materials and has achieved promising results albeit not yet approaching the spectacular performance of APbI3 materials. In this comment, we summarize the present status and future prospects for Pb-free perovskite materials and their devices.
Electric and Magnetic Hotspots via Hollow InSb Microspheres for Enhanced Terahertz Spectroscopy
Authors: Sadrara Mahdiyeh , Miri MirFaez
Published: February 2019

We study electric and magnetic hotspots in the gap between hollow InSb microspheres forming dimers and trimers. The outer radius, core volume fraction, distance, and temperature of the microspheres can be chosen to achieve field enhancement at a certain frequency corresponding to the transition between energy levels of a molecule placed in the gap. For example, utilizing 80 μm radius spheres at a gap of 2 μm held at a temperature of 295 K, allow electric field intensity enhancements of 10–2880 and magnetic field intensity enhancements of 3–61 in the frequency window 0.35–1.50 THz. The core volume fraction and the ambient temperature affect the enhancements, particularly in the frequency window 1.5–2 THz. Electric and magnetic hotspots are promising for THz absorption and circular dichroism spectroscopy.
Determination of non-metallic inclusions in a continuous casting slab of ultra-low carbon interstitial free steel by applying of metallographic method, electrolytic method and RTO technique
Authors: Guo Jing , Cheng Shu-sen , Guo Hanjie , Mei Yaguang
Published: February 2019

Metallographic, electrolytic method and RTO(room temperature organic) technique were applied in the present study to more accurately determine non-metallic inclusion in a ultra-low carbon interstitial free(IF) steel and further to confirm their origination in a Compact Strip Production Process (CSP Process) continuous casting (CC) slab. Results show that inclusions detected by metallographic method usually appear relative smaller size and are mainly Al2O3 based or TiN based in composition, whereas those extracted by electrolytic method usually have larger size and are much more calcium-silicate based in composition. In addition, inner structures of extracted inclusions were detected by applying of RTO technique. The large size calcium-silicate based inclusions are confirmed high possibilities originating from mold flux and/or tundish flux entrapment, which are less affected by the liquid steel composition; while the smaller ones are generally endogenous inclusion precipitating during the refining or solidification process that strongly depending on the liquid steel composition and temperature.
Insights into physiological roles of unique metabolites released from Plasmodium-infected RBCs and their potential as clinical biomarkers for malaria
Authors: Beri Divya , Ramdani Ghania , Balan Balu , Gadara Darshak , Poojary Mukta , Momeux Laurence , Tatu Utpal , Langsley Gordon
Published: February 2019

Plasmodium sp. are obligate intracellular parasites that derive most of their nutrients from their host meaning the metabolic circuitry of both are intricately linked. We employed untargeted, global mass spectrometry to identify metabolites present in the culture supernatants of P. falciparum-infected red blood cells synchronized at ring, trophozoite and schizont developmental stages. This revealed a temporal regulation in release of a distinct set of metabolites compared with supernatants of non-infected red blood cells. Of the distinct metabolites we identified pipecolic acid to be abundantly present in parasite lysate, infected red blood cells and infected culture supernatant. Further, we performed targeted metabolomics to quantify pipecolic acid concentrations in both the supernatants of red blood cells infected with P. falciparum, as well as in the plasma and infected RBCs of P. berghei-infected mice. Measurable and significant hyperpipecolatemia suggest that pipecolic acid has the potential to be a diagnostic marker for malaria.
Critical Functionality Effects from Storage Temperature on Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cell Suspensions
Authors: Kitahata Shohei , Tanaka Yuji , Hori Kanji , Kime Cody , Sugita Sunao , Ueda Hiroshi , Takahashi Masayo
Published: February 2019

Human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (hiPSC-RPE) cells suspension have the potential for regenerative treatment. However, practical regenerative applications with hiPSC-RPE cells require the development of simple and cost-effective non-freezing preservation methods. We investigated the effect of non-freezing temperatures on suspended hiPSC-RPE cells in various conditions and analysed mechanisms of cell death, anoikis, Rho GTPases, hypoxia, microtubule destruction, and cell metabolism. Cells stored at 37 °C had the lowest viability due to hypoxia from high cell metabolism and cell deposits, and cells preserved at 4 °C were damaged via microtubule fragility. Cell suspensions at 16 °C were optimal with drastically reduced apoptosis and negligible necrosis. Moreover, surviving cells proliferated and secreted key proteins normally, compared to cells without preservation. hiPSC-RPE cell suspensions were optimally preserved at 16 °C. Temperatures above or below the optimal temperature decreased cell viability significantly yet differentially by mechanisms of cell death, cellular metabolism, microtubule destruction, and oxygen tension, all relevant to cell conditions. Surviving cells are expected to function as grafts where high cell death is often reported. This study provides new insight into various non-freezing temperature effects on hiPSC-RPE cells that are highly relevant to clinical applications and may improve cooperation between laboratories and hospitals.
Peculiar elastic behavior of mechanical metamaterials with various minimal surfaces
Authors: Park Jun-Hyoung , Lee Jae-Chul
Published: February 2019

Molecular dynamics simulations were performed on nanostructured metamaterials (NMs) with gyroid, diamond, and primitive structures to evaluate their mechanical behavior, especially elastic properties. Unlike the constant nature of Young’s (E) and shear (μ) moduli of bulk materials, the values of both E and μ of NMs change with relative density and cell size but at different rates depending on the morphologies of the structure. This is particularly the case for μ; for a given relative density and cell size of NMs, the μ values differ greatly, depending on the types of structure, causing the NMs to display differing μ/E values and thus resistance to shear deformation. The mechanistic origin of this observation was analyzed by resolving the morphologies of the NMs in terms of the numbers and orientations of the fundamental structural motifs for constructing metamaterials.
Novel Chitohexaose Analog Protects Young and Aged mice from CLP Induced Polymicrobial Sepsis
Authors: Das Pragnya , Panda Santosh K. , Agarwal Beamon , Behera Sumita , Ali Syed M. , Pulse Mark E. , Solomkin Joseph S. , Opal Steven M. , Bhandari Vineet , Acharya Suchismita
Published: February 2019

In Gram-negative bacterial sepsis, production of excess pro-inflammatory cytokines results in hyperinflammation and tissue injury. Anti-inflammatory cytokines such as IL-10 inhibit inflammation and enhance tissue healing. Here, we report a novel approach to treat septicemia associated with intra-abdominal infection in a murine model by delicately balancing pro- and anti-inflammatory cytokines. A novel oligosaccharide compoundAVR-25selectively binds to the TLR4 protein (IC50 = 0.15 µM) in human peripheral blood monocytes and stimulates IL-10 production. Following the cecal ligation and puncture (CLP) procedure, intravenous dosing ofAVR-25(10 mg/kg, 6–12 h post-CLP) alone and in combination with antibioticimipenemprotected both young adult (10–12 week old) and aged (16–18 month old) mice against polymicrobial infection, organ dysfunction, and death. Proinflammatory cytokines (TNF-α, MIP-1, i-NOS) were decreased significantly and restoration of tissue damage was observed in all organs. A decrease in serum C-reactive protein (CRP) and bacterial colony forming unit (CFU) confirmed improved bacterial clearance. Together, these findings demonstrate the therapeutic ability ofAVR-25to mitigate the storm of inflammation and minimize tissue injury with high potential for adjunctive therapy in intra-abdominal sepsis.
Modelling and Analyzing Virus Mutation Dynamics of Chikungunya Outbreaks
Authors: Feng Xiaomei , Huo Xi , Tang Biao , Tang Sanyi , Wang Kai , Wu Jianhong
Published: February 2019

Chikungunya fever, caused by chikungunya virus (CHIKV) and transmitted to humans by infectedAedesmosquitoes, has posed a global threat in several countries in 2015. Recent outbreaks in La Réunion, Italy and China are related with a new variant of CHIKV with shorter extrinsic incubation period in contaminated mosquitoes, but the role of this new variant on the spread of chikungunya fever is unclear. We develop a mathematical model that incorporates the virus mutation dynamics in the transmission of CHIKV among mosquitoes and humans. Our numerical simulations show that a substantial virus mutation rate combined with high virus transmission probabilities from mosquito to human, could result in sustainable chikungunya fever outbreaks. Further, we apply Markov Chain Monte Carlo sampling method to fit our model to the 2007 chikungunya fever outbreak data in North-Eastern Italy where the mutant strain was detected. We conclude that the basic reproduction number might be underestimated without considering the mutation dynamics, and our estimation shows that the basic reproduction number of the 2007 Italy outbreak was$${\pmb{\mathscr{R}}}_{{\bf{0}}}$$R0 = 2.035[95%Cl: 1.9424 - 2.1366]. Sensitivity analysis shows that the transmission rate of the mutant strain from mosquitoes to human is more influential on$${\pmb{\mathscr{R}}}_{{\bf{0}}}$$R0than the shortened extrinsic incubation period. We conclude that the virus mutation dynamics could play an important role in the transmission of CHIKV, and there is a crucial need to better understand the mutation mechanism.
Iron-polyphenol complexes cause blackening upon grinding Hermetia illucens (black soldier fly) larvae
Authors: Janssen Renske H. , Canelli Greta , Sanders Mark G. , Bakx Edwin J. , Lakemond Catriona M. M. , Fogliano Vincenzo , Vincken Jean-Paul
Published: February 2019

Insects are a promising alternative protein source. One of the bottlenecks in applying insects in food is the fast darkening initiated during grinding. Besides enzymatic browning, non-enzymatic factors can cause off-colour formation, which differs between species. This study investigates the impact of iron, phenoloxidase, and polyphenols on off-colour formation in insect larvae. Hermetia illucens showed a blackish colour, whereas Tenebrio molitor turned brown and Alphitobius diaperinus remained the lightest. This off-colour formation appeared correlated with the iron content in the larvae, which was 61 ± 9.71, 54 ± 1.72 and 221 ± 6.07 mg/kg dw for T. molitor, A. diaperinus and H. illucens, respectively. In model systems, the formation of iron-L-3,4-dihydroxyphenylalanine (L-DOPA) bis- and tris-complexes were evidenced by direct injection into ESI-TOF-MS, based on their charges combined with iron isotope patterns. The reversibility of the binding of iron to phenolics, and thereby loss of blackening, was confirmed by EDTA addition. Besides complex formation, oxidation of L-DOPA by redox reactions with iron occurred mainly at low pH, whereas auto-oxidation of L-DOPA mainly occurred at pH 10. Tyrosinase (i.e. phenoloxidase) activity did not change complex formation. The similarity in off-colour formation between the model system and insects indicated an important role for iron-phenolic complexation in blackening.
Unintentional injury mortality among children under age five in urban and rural areas in the Sichuan province of west China, 2009–2017
Authors: Yao Minghong , Wu Gonghua , Zhao Ziling , Luo Min , Zhang Juying
Published: February 2019

This study analysed trends in the unintentional injuries specific mortality rates among children under age five (UI-specific U5MRs) in urban and rural areas in the Sichuan province of western China. Data were obtained from the National Health Statistics Survey System. The Cochran-Armitage trend test was used to analyse the trends in UI-specific U5MRs and the proportion of unintentional injury deaths to total deaths. The Poisson regression model was used to compare the UI-specific U5MRs between rural and urban areas. The overall UI-specific U5MRs decreased from 3.8 to 1.7 per 1,000 live births from 2009 to 2017, with an average annual decline in the rates of 8.78% and 10.05% in urban and rural areas, respectively. The UI risk of death in rural areas was approximately 1.95 times that in urban areas (95% CI: 1.73–2.18; p < 0.01). A total of 49.9% of all the children in the study did not receive any treatment before death caused by UI. The UI-specific U5MRs significantly declined in Sichuan province from 2009 to 2017, but large disparities in UI-specific U5MRs in urban and rural areas still exist. Reducing the U5MRs due to UI should be a major public health concern in western China.
Integrative modeling reveals key chromatin and sequence signatures predicting super-enhancers
Authors: Khan Aziz , Zhang Xuegong
Published: February 2019

Super-enhancers (SEs) are clusters of transcriptional enhancers which control the expression of cell identity and disease-associated genes. Current studies demonstrated the role of multiple factors in SE formation; however, a systematic analysis to assess the relative predictive importance of chromatin and sequence features of SEs and their constituents is lacking. In addition, a predictive model that integrates various types of data to predict SEs has not been established. Here, we integrated diverse types of genomic and epigenomic datasets to identify key signatures of SEs and investigated their predictive importance. Through integrative modeling, we found Cdk8, Cdk9, and Smad3 as new features of SEs, which can define known and new SEs in mouse embryonic stem cells and pro-B cells. We compared six state-of-the-art machine learning models to predict SEs and showed that non-parametric ensemble models performed better as compared to parametric. We validated these models using cross-validation and also independent datasets in four human cell-types. Taken together, our systematic analysis and ranking of features can be used as a platform to define and understand the biology of SEs in other cell-types.
Semi-automated fabrication of customized ocular prosthesis with three–dimensional printing and sublimation transfer printing technology
Authors: Ko JaeSang , Kim So Hyun , Baek Seung Woon , Chae Min Kyung , Yoon Jin Sook
Published: February 2019

An ocular prosthesis is a custom-made polymeric insert that can be placed in an anophthalmic socket for cosmetic rehabilitation of patients who have lost their eyes. The process of creating such a custom-made ocular prosthesis is time-consuming and labor-intensive because it involves artistic work that is carried out manually. This paper proposes a novel semi-automated method for fabricating customized ocular prostheses using three-dimensional (3D) printing and sublimation transfer printing. In the proposed method, an impression mold of the patient’s anophthalmic socket is first optically scanned using a 3D scanner to produce a 3D model. The ocular prosthesis is then produced via a digital light processing 3D printer using biocompatible photopolymer resin. Subsequently, an image of the iris and blood vessels of the eye is prepared by modifying a photographed image of the contralateral normal eye, and printed onto the 3D-printed ocular prosthesis using a dye sublimation transfer technique. Cytotoxicity assessments of the base material and fabricated ocular prosthesis indicate that there is no adverse effect on cellular viability and proliferation. The proposed method reduces the time and skill required to fabricate a customized ocular prosthesis, and is expected to provide patients with easier access to quality custom-made ocular prostheses.
MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants
Authors: Venter Marianne , Tomas Cara , Pienaar Ilse S. , Strassheim Victoria , Erasmus Elardus , Ng Wan-Fai , Howell Neil , Newton Julia L. , Van der Westhuizen Francois H. , Elson Joanna L.
Published: February 2019

Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (CFS) is a debilitating condition. There is growing interest in a possible etiologic or pathogenic role of mitochondrial dysfunction and mitochondrial DNA (mtDNA) variation in ME/CFS. Supporting such a link, fatigue is common and often severe in patients with mitochondrial disease. We investigate the role of mtDNA variation in ME/CFS. No proven pathogenic mtDNA mutations were found. We then investigated population variation. Two cohorts were analysed, one from the UK (n = 89 moderately affected; 29 severely affected) and the other from South Africa (n = 143 moderately affected). For both cohorts, ME/CFS patients had an excess of individuals without a mildly deleterious population variant. The differences in population variation might reflect a mechanism important to the pathophysiology of ME/CFS.
Hippocampal neurogenesis regulates recovery of defensive responses by recruiting threat- and extinction-signalling brain networks
Authors: Martínez-Canabal Alonso , López-Oropeza Grecia , Gaona-Gamboa Abril , Ballesteros-Zebadua Paola , de la Cruz Olinca Galvan , Moreno-Jimenez Sergio , Sotres-Bayon Francisco
Published: February 2019

Safe exposure to a context that was previously associated with threat leads to extinction of defensive responses. Such contextual fear extinction involves the formation of a new memory that inhibits a previously acquired contextual fear memory. However, fear-related responses often return with the simple passage of time (spontaneous fear recovery). Given that contextual fear and extinction memories are hippocampus-dependent and hippocampal neurogenesis has been reported to modify preexisting memories, we hypothesized that neurogenesis-mediated modification of preexisting extinction memory would modify spontaneous fear recovery. To test this, rats underwent contextual fear conditioning followed by extinction. Subsequently, we exposed rats to an enriched environment or focal X-irradiation to enhance or ablate hippocampal neurogenesis, respectively. Over a month later, rats were tested to evaluate spontaneous fear recovery. We found that enhancing neurogenesis after, but not before, extinction prevented fear recovery. In contrast, neurogenesis ablation after, but not before, extinction promoted fear recovery. Using the neuronal activity marker c-Fos, we identified brain regions recruited in these opposing neurogenesis-mediated changes during fear recovery. Together, our findings indicate that neurogenesis manipulation after extinction learning modifies fear recovery by recruiting brain network activity that mediates the expression of preexisting contextual fear and extinction memories.
Gold-Plated Electrode with High Scratch Strength for Electrophysiological Recordings
Authors: Vafaiee Mohaddeseh , Vossoughi Manouchehr , Mohammadpour Raheleh , Sasanpour Pezhman
Published: February 2019

Multi electrode arrays (MEA) have been exploited in different electrophysiological applications. In neurological applications, MEAs are the vital interfaces between neurons and the electronic circuits with dual role; transmitting electric signal to the neurons and converting neural activity to the electric signal. Since the performance of the electrodes has a direct effect on the quality of the recorded neuronal signal, as well as the stimulation, the true choice of electrode material for MEA is crucial. Gold is one of the best candidates for fabrication of MEAs due to its high electrical conductivity, biocompatibility and good chemical stability. However, noble metals such as gold do not adhere well to the glass substrate. Consequently while exposing to the water, gold films are damaged, which impose limitations in the exploiting of gold thin films as the electrode. In this paper, a simple and cost effective method for the fabrication of gold electrode arrays is proposed. Using various mechanical (adhesion test and scratch strength), morphological (AFM and SEM) and electrochemical methods, the fabricated electrodes are characterized. The results show that the fabricated electrode arrays have significantly high scratch strength and stability within the aqueous medium. In addition, the electrical properties of the electrodes have been improved. The proposed electrodes have the potential to be exploited in other applications including electronics, electrochemistry, and biosensors.
Object-based attention in complex, naturalistic auditory streams
Authors: Marinato Giorgio , Baldauf Daniel
Published: February 2019

In vision,objectshave been described as the ‘units’ on which non-spatial attention operates in many natural settings. Here, we test the idea of object-based attention in the auditory domain within ecologically valid auditory scenes, composed of two spatially and temporally overlapping sound streams (speech signal vs. environmental soundscapes in Experiment 1 and two speech signals in Experiment 2). Top-down attention was directed to one or the other auditory stream by a non-spatial cue. To test for high-level, object-based attention effects we introduce an auditoryrepetition detection taskin which participants have to detect brief repetitions of auditory objects, ruling out any possible confounds with spatial or feature-based attention. The participants’ responses were significantly faster and more accurate in the valid cue condition compared to the invalid cue condition, indicating a robust cue-validity effect of high-level, object-based auditory attention.
Investigating the relationship between district-level socioeconomic status and individual obesity in Taiwanese adolescents: A large-scale cross-sectional analysis
Authors: Ni Ying-Lien , Chang Jen-Ho , Chen Lung Hung
Published: February 2019

The current study aimed to assess the prevalence of obesity and to explore the relationship between socioeconomic status and obesity among adolescents in Taiwan, a transitioning country. Data from the Taiwan School Physical Fitness Database on 1,875,627 Taiwanese adolescents aged 10–18 years were analyzed. The average family income per household in each district was collected from the national statistical institutional database. Descriptive statistics, Chi-square tests, Pearson correlation analysis, and mixed model analyses were used. The overall prevalence of combined overweight and obesity was 28.1%. The prevalence of overweight/obesity significantly differed according to gender and age. Furthermore, the average family income per household was negatively associated with the district-level prevalence of obesity. Additionally, when controlling for physical fitness, the average family income per household remained negatively associated with adolescent obesity. In addition, multilevel analysis was also applied to explore the relationship between district-level socioeconomic status and individual-level obesity to prevent the nested data structure from affecting the results. The results revealed that the average family income per household negatively correlated with individual obesity. These findings provide insight for public health officials into preventing and managing adolescent obesity.
Personality-dependent breeding dispersal in rural but not urban burrowing owls
Authors: Luna Álvaro , Palma Antonio , Sanz-Aguilar Ana , Tella José L. , Carrete Martina
Published: February 2019

Dispersal propensity has been correlated with personality traits, conspecific density and predation risk in a variety of species. Thus, changes in the relative frequency of behavioural phenotypes or in the ecological pressures faced by individuals in contrasting habitats can have unexpected effects on their dispersal strategies. Here, using the burrowing owl Athene cunicularia as a study model, we test whether changes in the behavioural profile of individuals and changes in conspecific density and predation pressure associated with urban life influence their breeding dispersal decisions compared to rural conspecifics. Our results show that breeding dispersal behaviour differs between rural and urban individuals. Site fidelity was lower among rural than among urban birds, and primarily related to an individual’s behaviours (fear of humans), which has been reported to reflect individual personality. In contrast, the main determinant of site fidelity among urban owls was conspecific density. After taking the decision of dispersing, urban owls moved shorter distances than rural ones, with females dispersing farther than males. Our results support a personality-dependent dispersal pattern that might vary with predation risk. However, as multiple individuals of two populations (one urban, one rural) were used for this research, differences can thus also be caused by other factors differing between the two populations. Further research is needed to properly understand the ecological and evolutionary consequences of changes in dispersal behaviours, especially in terms of population structuring and gene flow between urban and rural populations.
Analysis of Differentially Expressed Genes in Tissues of Camellia sinensis during Dedifferentiation and Root Redifferentiation
Authors: Gao Ying , Zhao Min , Wu Xiao-Han , Li Da , Borthakur Devajit , Ye Jian-Hui , Zheng Xin-Qiang , Lu Jian-Liang
Published: February 2019

Tissue culture is very important for identifying the gene function of Camellia sinensis (L.) and exploiting novel germplasm through transgenic technology. Regeneration system of tea plant has been explored but not been well established since the molecular mechanism of tea plant regeneration is not clear yet. In this study, transcriptomic analysis was performed in the initial explants of tea plant and their dedifferentiated and redifferentiated tissues. A total of 93,607 unigenes were obtained through de novo assembly, and 7,193 differentially expressed genes (DEGs) were screened out from the 42,417 annotated unigenes. Much more DEGs were observed during phase transition rather than at growth stages of callus. Our KOG and KEGG analysis, and qPCR results confirmed that phase transition of tea plant was closely related to the mechanism that regulate expression of genes encoding the auxin- and cytokinin-responsive proteins, transcription factor MYB15 and ethylene-responsive transcription factor ERF RAP2-12. These findings provide a reliable foundation for elucidating the mechanism of the phase transition and may help to optimize the regeneration system by regulating the gene expression pattern.
Reprogrammable Graphene-based Metasurface Mirror with Adaptive Focal Point for THz Imaging
Authors: Hosseininejad Seyed Ehsan , Rouhi Kasra , Neshat Mohammad , Faraji-Dana Reza , Cabellos-Aparicio Albert , Abadal Sergi , Alarcón Eduard
Published: February 2019

Recent emergence of metasurfaces has enabled the development of ultra-thin flat optical components through different wavefront shaping techniques at various wavelengths. However, due to the non-adaptive nature of conventional metasurfaces, the focal point of the resulting optics needs to be fixed at the design stage, thus severely limiting its reconfigurability and applicability. In this paper, we aim to overcome such constraint by presenting a flat reflective component that can be reprogrammed to focus terahertz waves at a desired point in the near-field region. To this end, we first propose a graphene-based unit cell with phase reconfigurability, and then employ the coding metasurface approach to draw the phase profile required to set the focus on the target point. Our results show that the proposed component can operate close to the diffraction limit with high focusing range and low focusing error. We also demonstrate that, through appropriate automation, the reprogrammability of the metamirror could be leveraged to develop compact terahertz scanning and imaging systems, as well as novel reconfigurable components for terahertz wireless communications.