bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanosomes in pigmented epithelia maintain eye lens transparency during zebrafish embryonic development
Authors: Takamiya Masanari , Xu Feng , Suhonen Heikki , Gourain Victor , Yang Lixin , Ho Nga Yu , Helfen Lukas , Schröck Anne , Etard Christelle , Grabher Clemens , Rastegar Sepand , Schlunck Günther , Reinhard Thomas , Baumbach Tilo , Strähle Uwe 
Published: May 2016

AbstractAltered levels of trace elements are associated with increased oxidative stress that is eventually responsible for pathologic conditions. Oxidative stress has been proposed to be involved in eye diseases, including cataract formation. We visualized the distribution of metals and other trace elements in the eye of zebrafish embryos by micro X-ray fluorescence (μ-XRF) imaging. Many elements showed highest accumulation in the retinal pigment epithelium (RPE) of the zebrafish embryo. Knockdown of the zebrafish brown locus homologues tyrp1a/b eliminated accumulation of these elements in the RPE, indicating that they are bound by mature melanosomes. Furthermore, albino (slc45a2) mutants, which completely lack melanosomes, developed abnormal lens reflections similar to the congenital cataract caused by mutation of the myosin chaperon Unc45b, and an in situ spin trapping assay revealed increased oxidative stress in the lens of albino mutants. Finally transplanting a wildtype lens into an albino mutant background resulted in cataract formation. These data suggest that melanosomes in pigment epithelial cells protect the lens from oxidative stress during embryonic development, likely by buffering trace elements.
The G protein-coupled receptor GPR157 regulates neuronal differentiation of radial glial progenitors through the Gq-IP3 pathway
Authors: Takeo Yutaka , Kurabayashi Nobuhiro , Nguyen Minh Dang , Sanada Kamon 
Published: May 2016

AbstractThe ability of radial glial progenitors (RGPs) to generate cortical neurons is determined by local extracellular factors and signaling pathways intrinsic to RGPs. Here we find that GPR157, an orphan G protein-coupled receptor, localizes to RGPs’ primary cilia exposed to the cerebrospinal fluid (CSF). GPR157 couples with Gq-class of the heterotrimeric G-proteins and signals through IP3-mediated Ca2+ cascade. Activation of GPR157-Gq signaling enhances neuronal differentiation of RGPs whereas interfering with GPR157-Gq-IP3 cascade in RGPs suppresses neurogenesis. We also detect the presence of putative ligand(s) for GPR157 in the CSF and demonstrate the increased ability of the CSF to activate GPR157 at neurogenic phase. Thus, GPR157-Gq signaling at the primary cilia of RGPs is activated by the CSF and contributes to neurogenesis.
Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease
Authors: Bell Catherine C. , Hendriks Delilah F. G. , Moro Sabrina M. L. , Ellis Ewa , Walsh Joanne , Renblom Anna , Fredriksson Puigvert Lisa , Dankers Anita C. A. , Jacobs Frank , Snoeys Jan , Sison-Young Rowena L. , Jenkins Rosalind E. , Nordling Åsa , Mkrtchian Souren , Park B. Kevin , Kitteringham Neil R. , Goldring Christopher E. P. , Lauschke Volker M. , Ingelman-Sundberg Magnus 
Published: May 2016

AbstractLiver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.
Neuroprotective effects of the anticancer drug NVP-BEZ235 (dactolisib) on amyloid-β 1–42 induced neurotoxicity and memory impairment
Authors: Bellozi Paula Maria Quaglio , Lima Isabel Vieira de Assis , Dória Juliana Guimarães , Vieira Érica Leandro Marciano , Campos Alline Cristina , Candelario-Jalil Eduardo , Reis Helton José , Teixeira Antônio Lúcio , Ribeiro Fabíola Mara , de Oliveira Antônio Carlos Pinheiro 
Published: May 2016

AbstractAlzheimer’s Disease (AD) is a progressive neurodegenerative disease and the main cause of dementia. Substantial evidences indicate that there is over-activation of the PI3K/Akt/mTOR axis in AD. Therefore, the aim of the present study was to investigate the effects of NVP-BEZ235 (BEZ; dactolisib), a dual PI3K/mTOR inhibitor that is under phase I/II clinical trials for the treatment of some types of cancer, in hippocampal neuronal cultures stimulated with amyloid-β (Aβ) 1–42 and in mice injected with Aβ 1–42 in the hippocampus. In cell cultures, BEZ reduced neuronal death induced by Aβ. BEZ, but not rapamycin, a mTOR inhibitor, or LY294002, a PI3K inhibitor that also inhibits mTOR, reduced the memory impairment induced by Aβ. The effect induced by Aβ was also prevented in PI3Kγ−/− mice. Neuronal death and microgliosis induced by Aβ were reduced by BEZ. In addition, the compound increased IL-10 and TNF-α levels in the hippocampus. Finally, BEZ did not change the phosphorylation of Akt and p70s6K, suggesting that the involvement of PI3K and mTOR in the effects induced by BEZ remains controversial. Therefore, BEZ represents a potential strategy to prevent the pathological outcomes induced by Aβ and should be investigated in other models of neurodegenerative conditions.
Self-assembly of MPG1, a hydrophobin protein from the rice blast fungus that forms functional amyloid coatings, occurs by a surface-driven mechanism
Authors: Pham Chi L. L. , Rey Anthony , Lo Victor , Soulès Margaux , Ren Qin , Meisl Georg , Knowles Tuomas P. J. , Kwan Ann H. , Sunde Margaret 
Published: May 2016

AbstractRice blast is a devastating disease of rice caused by the fungus Magnaporthe oryzae and can result in loss of a third of the annual global rice harvest. Two hydrophobin proteins, MPG1 and MHP1, are highly expressed during rice blast infections. These hydrophobins have been suggested to facilitate fungal spore adhesion and to direct the action of the enzyme cutinase 2, resulting in penetration of the plant host. Therefore a mechanistic understanding of the self-assembly properties of these hydrophobins and their interaction with cutinase 2 is crucial for the development of novel antifungals. Here we report details of a study of the structure, assembly and interactions of these proteins. We demonstrate that, in vitro, MPG1 assembles spontaneously into amyloid structures while MHP1 forms a non-fibrillar film. The assembly of MPG1 only occurs at a hydrophobic:hydrophilic interface and can be modulated by MHP1 and other factors. We further show that MPG1 assemblies can much more effectively retain cutinase 2 activity on a surface after co-incubation and extensive washing compared with other protein coatings. The assembly and interactions of MPG1 and MHP1 at hydrophobic surfaces thereby provide the basis for a possible mechanism by which the fungus can develop appropriately at the infection interface.
Combination of ESI and MALDI mass spectrometry for qualitative, semi-quantitative and in situ analysis of gangliosides in brain
Authors: Zhang Yangyang , Wang Jun , Liu Jian’an , Han Juanjuan , Xiong Shaoxiang , Yong Weidong , Zhao Zhenwen 
Published: May 2016

AbstractGangliosides are a family of complex lipids that are abundant in the brain. There is no doubt the investigations about the distribution of gangliosides in brian and the relationship between gangliosides and Alzheimer’s disease is profound. However, these investigations are full of challenges due to the structural complexity of gangliosides. In this work, the method for efficient extraction and enrichment of gangliosides from brain was established. Moreover, the distribution of gangliosides in brain was obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). It was found that 3-aminoquinoline (3-AQ) as matrix was well-suited for MALDI MS analysis of gangliosides in negative ion mode. In addition, the pretreatment by ethanol (EtOH) cleaning brain section and the addition of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI analysis was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was respectively acquired by electrospray ionization (ESI) MS and MALDI MSI and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technology, the distribution of gangliosides in amyloid precursor protein transgenic mouse brain was obtained, which may provide a new insight for bioresearch of Alzheimer’s disease (AD).
A meta-analytical assessment of STK39 three well-defined polymorphisms in susceptibility to hypertension
Authors: Yang Hualing , Ye Lingyang , Wang Qingxiang , Cai Dongmiao , Chen Qumin , Pan Hongming , Wang Zhanxiang 
Published: May 2016

AbstractSerine/threonine kinase 39 gene (STK39) is one of the promising hypertension-susceptibility genes identified by a genome-wide association study in 2009, whereas subsequent validation in other ethnic groups is unsatisfactory, with inconsistent and inconclusive findings. We therefore aimed to meta-analytically assess the risk prediction of STK39 three polymorphisms, rs6749447, rs35929607 and rs3754777, for primary hypertension. Literature search and data collection were independently completed by two authors. Nine articles were pooled in this study. Overall analyses failed to see any significant associations of rs6749447, rs35929607 and rs3754777 with hypertension risk (odds ratio: 1.27, 0.95 and 1.21; P = 0.270, 0.507 and 0.153, respectively) and there was evident heterogeneity for three comparisons (I2 > 80%). Meta-regression analyses indicated that smoking was a significant risk factor for the association of rs3754777 with hypertension (P = 0.017). As reflected by the Begg’s and Filled funnel plots, as well as Egger’s tests, there were low probabilities of publication bias. In conclusion, our meta-analytical findings suggest that STK39 might not be a hypertension-susceptibility gene.
Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response
Authors: Saito Yoshimasa , Nakaoka Toshiaki , Sakai Kasumi , Muramatsu Toshihide , Toshimitsu Kohta , Kimura Masaki , Kanai Takanori , Sato Toshiro , Saito Hidetsugu 
Published: May 2016

AbstractRecent studies have proposed that the major anti-tumor effect of DNA methylation inhibitors is induction of interferon-responsive genes via dsRNAs-containing endogenous retroviruses. Recently, a 3D culture system for stem cells known as organoid culture has been developed. Lgr5-positive stem cells form organoids that closely recapitulate the properties of original tissues. To investigate the effect of DNA demethylation on tumor organoids, we have established organoids from intestinal tumors of ApcMin/+(Min) mice and subjected them to 5-aza-2′-deoxycytidine (5-Aza-CdR) treatment and Dnmt1 knockdown. DNA demethylation induced by 5-Aza-CdR treatment and Dnmt1 knockdown significantly reduced the cell proliferation of the tumor organoids. Microarray analyses of the tumor organoids after 5-Aza-CdR treatment and Dnmt1 knockdown revealed that interferon-responsive genes were activated by DNA demethylation. Gene ontology and pathway analyses clearly demonstrated that these genes activated by DNA demethylation are involved in the anti-viral response. These findings indicate that DNA demethylation suppresses the proliferation of intestinal tumor organoids by inducing an anti-viral response including activation of interferon-responsive genes. Treatment with DNA methylation inhibitors to activate a growth-inhibiting immune response may be an effective therapeutic approach for colon cancers.
Superior thermal conductivity in suspended bilayer hexagonal boron nitride
Authors: Wang Chengru , Guo Jie , Dong Lan , Aiyiti Adili , Xu Xiangfan , Li Baowen 
Published: May 2016

AbstractWe reported the basal-plane thermal conductivity in exfoliated bilayer hexagonal boron nitride h-BN that was measured using suspended prepatterned microstructures. The h-BN sample suitable for thermal measurements was fabricated by dry-transfer method, whose sample quality, due to less polymer residues on surfaces, is believed to be superior to that of PMMA-mediated samples. The measured room temperature thermal conductivity is around 484 Wm−1K−1(+141 Wm−1K−1/ −24 Wm−1K−1) which exceeds that in bulk h-BN, providing experimental observation of the thickness-dependent thermal conductivity in suspended few-layer h-BN.
Femtosecond laser filament induced condensation and precipitation in a cloud chamber
Authors: Ju Jingjing , Liu Jiansheng , Liang Hong , Chen Yu , Sun Haiyi , Liu Yonghong , Wang Jingwei , Wang Cheng , Wang Tiejun , Li Ruxin , Xu Zhizhan , Chin See Leang 
Published: May 2016

AbstractA unified picture of femtosecond laser induced precipitation in a cloud chamber is proposed. Among the three principal consequences of filamentation from the point of view of thermodynamics, namely, generation of chemicals, shock waves and thermal air flow motion (due to convection), the last one turns out to be the principal cause. Much of the filament induced chemicals would stick onto the existing background CCN’s (Cloud Condensation Nuclei) through collision making the latter more active. Strong mixing of air having a large temperature gradient would result in supersaturation in which the background CCN’s would grow efficiently into water/ice/snow. This conclusion was supported by two independent experiments using pure heating or a fan to imitate the laser-induced thermal effect or the strong air flow motion, respectively. Without the assistance of any shock wave and chemical CCN’s arising from laser filament, condensation and precipitation occurred. Meanwhile we believe that latent heat release during condensation /precipitation would enhance the air flow for mixing.
Recovery und Inklusion: ein Erfahrungsbericht über 5 Jahre Genesungsbegleitung in der Psychiatrie
Authors: Eikmeier G. , Lacroix A. 
Published: May 2016

ZusammenfassungWir berichten über unsere bisher 5-jährige Erfahrung mit der Einbeziehung von Psychiatrie-Erfahrenen als Genesungsbegleiter in die psychiatrischen Behandlungsteams am Klinikum Bremerhaven-Reinkenheide. Ziel war es den Betroffenen durch Erfahrung die Möglichkeit einer beruflichen Inklusion zu bieten und durch ihre Arbeit die Abteilung stärker nach Recovery-Grundsätzen auszurichten. Derzeit arbeiten 7 Genesungsbegleiter an der Abteilung. Sie sind fest angestellt und werden aus dem Pflegebudget bezahlt. Dargestellt werden die Voraussetzungen unseres Modells, die Umsetzung, die eingetretenen Veränderungen, aber auch die dabei aufgetretenen Probleme.
Wie sind Kinder- und Jugendkliniken in Nordrhein-Westfalen auf die Überwindung von Sprachbarrieren vorbereitet? – Eine Pilotstudie zur Strukturqualität in der stationären Gesundheitsversorgung
Authors: Langer T. , Zapf T. , Wirth S. , Meyer B. , Wiegand A. , Timmen H. , Gupta S. , Schuster S. , Geraedts M. 
Published: May 2016

Zusammenfassung
Ziel der Studie Der Anteil von Kindern mit Migrationshintergrund unter 5 Jahren liegt bundesweit bei 35%, in Nordrhein-Westfalen (NRW) bei 43%. Häufig sind mit dem Migrationshintergrund unzureichende Deutschkenntnisse bei einem oder beiden Elternteilen verbunden. Kommunikationsbarrieren durch Sprachdifferenzen haben einen negativen Einfluss auf die Behandlungsqualität, Patientensicherheit und Behandlungskosten. Es wird untersucht, wie Kinder- und Jugendkliniken auf die Herausforderung durch Sprachbarrieren vorbereitet sind.
Methodik Wir führten eine Querschnittsbefragung aller Kinderkliniken in NRW durch und luden dazu die Klinikdirektoren schriftlich und per email zur Teilnahme ein. Der Fragebogen orientierte sich an den „Standards for Culturally and Linguistically Appropriate Services in Health and Health Care“ (CLAS) und wurde an die deutschen Verhältnisse angepasst.
Ergebnisse 38 Kliniken nahmen teil (51%). Sprachbarrieren kommen häufig vor (bei 75% der Antwortenden mehr als 10% der Patienten). 82% der Antwortenden sehen ihre Klinik schlechter als „gut“ auf die Überwindung von Sprachbarrieren vorbereitet. Die Feststellung des Dolmetscherbedarfs erfolgt bei der Mehrheit (61%) „fall-abhängig“ und nicht einem Protokoll folgend. Zur Überwindung von Sprachbarrieren werden überwiegend mehrsprachige Mitarbeiter eingesetzt, wobei nur 38% eine Liste von mehrsprachigen Mitarbeitern als ausreichende Ressource bewerten. Die Kosten, die für professionelle Dolmetscher entstehen, waren 42% der Antwortenden nicht bekannt. In den übrigen Fällen betrugen sie weniger als € 500/Monat.
Schlussfolgerung Die Überwindung von Sprachbarrieren erfolgt unter Einsatz lokaler Ressourcen, die aus Sicht der Mehrheit der Antwortenden nicht ausreichen. Die Entwicklung von Qualitätsstandards und Bereitstellung finanzieller Mittel sind notwendig, um das Verbesserungspotenzial zu mobilisieren. Hierfür sind Untersuchungen in anderen Disziplinen und Sektoren notwendig, um in einen Dialog mit Entscheidungsträgern aus Politik und Krankenkassen zu treten.
Biomechanical analysis of different starting strategies utilized during cross‐country skiing starts
Authors: Wiltmann Victor Wennemar , Holmberg Hans‐Christer , Pelttari Pasi , Mikkola Jussi , Häkkinen Keijo , Ohtonen Olli , Linnamo Vesa 
Published: May 2016

AbstractThe present study was designed to analyse and compare the kinetics and kinematics associated with three different starting strategies during classic cross‐country ski racing. Inside a ski tunnel, 12 elite male skiers performed three sets of three 38 m starts. Each set included one start using: double poling only (DP), diagonal stride only (DIA) and freely chosen (FREE) (i.e. where subjects used the strategy or combination of strategies they felt was fastest) in random order. The first 18 m was performed on a series of force plates that measured horizontal and vertical forces followed by 20 m of a standard snow track. Additionally, cycle characteristics and joint angles were measured. DIA and FREE were faster over 38 m than DP (P < .01). Net horizontal impulse (taking into account both positive and negative impulses) 5–10 m after the start was lower during DP than during DIA and FREE (both P < .05). All subjects skied faster when using only DIA for the entire 38 m. Furthermore, the sum duration and frequency of propulsive contacts over the first 18 m was less in DP than DIA and FREE (P < .01). In conclusion, differences between the starting strategies examined was especially pronounced during the initial cycles. Transition from DIA to DP during the start also slowed the skiers, but optimal timing for such a transition was not elucidated.
Isomon instabilities driven by energetic ions in Wendelstein 7-X
Authors: Kolesnichenko Ya.I. , Könies A. , Lutsenko V.V. , Drevlak M. , Turkin Yu. , Helander P. 
Published: May 2016

Abstract
It is found that modes of Alfvénic character affected by plasma compressibility and having equal poloidal and toroidal mode numbers (named ‘isomon modes’) can exist in W7-X. These modes, and the conditions under which they arise, are sensitive to the magnitude of the rotational transform of the field lines and the presence of energetic ions. The energetic ions produced by neutral-beam injection (having the energy 55–60 keV) interact resonantly with large-scale isomon modes (

m
=
n
≪
10

), which tends to lead to instabilities extending over a large part of the plasma cross section.
Interrelationships Among Various Measures of Central Artery Stiffness
Authors: Lim Jisok , Pearman Miriam , Park Wonil , Alkatan Mohammed , Tanaka Hirofumi 
Published: May 2016

Abstract

BACKGROUND
A number of different techniques and methodologies have been applied to quantify stiffness of arteries. Because measures of arterial stiffness differ in regards to measurement locations as well as properties, it is not clear how well these measures that are supposed to reflect the same arterial wall properties are related.

METHODS
Interrelationships between different measures of arterial stiffness were evaluated in 50 apparently healthy subjects varying in age.

RESULTS
Significant relations ranging from mild to strong were observed among measures of arterial stiffness while some measures were not significantly associated. Cardio-ankle vascular index (CAVI) was significantly associated with carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV). Ultrasound-derived measures of arterial stiffness (e.g., compliance, distensibility) were weakly or not significantly related to pulse wave velocity (PWV) measures. The limits of agreement between each of arterial stiffness measures based on the Bland–Altman analyses indicate that there were close agreements (CI = 1.12–1.52) between CAVI, cfPWV, and baPWV. However, agreements between PWV measures and ultrasound-derived measures were mild to moderate. β-stiffness index demonstrated large 95% CIs with other measures. When associations between relative changes in various measures of arterial stiffness in response to isometric handgrip exercise were evaluated, the general trend of associations was similar to the relations observed at rest. β-stiffness index was not related to most measures of arterial stiffness.

CONCLUSION
These results suggest that the techniques used to assess arterial stiffness may not be interchangeable in clinical and research settings and that comparisons of findings obtained with different arterial stiffness measures should be conducted with caution.