bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of the influence of TM6SF2 E167K variant on Plasma Concentration of Aminotransferases across different Populations and Diverse Liver Phenotypes
Authors: Sookoian Silvia , Pirola Carlos J. 
Published: June 2016

AbstractA nonsynonymous E167K (rs58542926 C/T) variant in TM6SF2 gene was recently associated with nonalcoholic fatty liver disease (NAFLD). We explored the association between E167K and plasma concentrations of alanine (ALT) and aspartate (AST) aminotransferases through a meta-analysis. We also estimated the strength of the effect across diverse liver phenotypes, including NAFLD and chronic viral hepatitis; fourteen studies were included. We found that ALT (p = 3.2 × 10−6, n = 94,414) and AST (p = 0007, n = 93,809) levels were significantly associated with rs58542926 in NAFLD. By contrast, rs58542926 was not associated with either ALT (p = 0.24, n = 4187) or AST (p = 0.17, n = 2678) levels in four studies on chronic hepatitis. In conclusion, the results of the pooled estimates in patients with NAFLD showed that carriers of the T allele (EK + KK), when compared with homozygous subjects for the C allele (EE genotype) have increased levels of aminotransferases; however, this increase represents –2.5 (9.8%) and 1.2 (5%) IU/L of ALT and AST respectively, which is fairly small compared with the large effect of PNPLA3- rs738409-G allele that is associated with a –28% increase in serum ALT.
Structure and function of chicken interleukin-1 beta mutants: uncoupling of receptor binding and in vivo biological activity
Authors: Chen Wen-Ting , Huang Wen-Yang , Chen Ting , Salawu Emmanuel Oluwatobi , Wang Dongli , Lee Yi-Zong , Chang Yuan-Yu , Yang Lee-Wei , Sue Shih-Che , Wang Xinquan , Yin Hsien-Sheng 
Published: June 2016

AbstractReceptor-binding and subsequent signal-activation of interleukin-1 beta (IL-1β) are essential to immune and proinflammatory responses. We mutated 12 residues to identify sites important for biological activity and/or receptor binding. Four of these mutants with mutations in loop 9 (T117A, E118K, E118A, E118R) displayed significantly reduced biological activity. Neither T117A nor E118K mutants substantially affected receptor binding, whereas both mutants lack the IL-1β signaling in vitro but can antagonize wild-type (WT) IL-1β. Crystal structures of T117A, E118A and E118K revealed that the secondary structure or surface charge of loop 9 is dramatically altered compared with that of wild-type chicken IL-1β. Molecular dynamics simulations of IL-1β bound to its receptor (IL-1RI) and receptor accessory protein (IL-1RAcP) revealed that loop 9 lies in a pocket that is formed at the IL-1RI/IL-1RAcP interface. This pocket is also observed in the human ternary structure. The conformations of above mutants in loop 9 may disrupt structural packing and therefore the stability in a chicken IL-1β/IL-1RI/IL-1RAcP signaling complex. We identify the hot spots in IL-1β that are essential to immune responses and elucidate a mechanism by which IL-1β activity can be inhibited. These findings should aid in the development of new therapeutics that neutralize IL-1 activity.
Carbon nanotubes affect the toxicity of CuO nanoparticles to denitrification in marine sediments by altering cellular internalization of nanoparticle
Authors: Zheng Xiong , Su Yinglong , Chen Yinguang , Wan Rui , Li Mu , Huang Haining , Li Xu 
Published: June 2016

AbstractDenitrification is an important pathway for nitrate transformation in marine sediments and this process has been observed to be negatively affected by engineered nanomaterials. However, previous studies only focused on the potential effect of a certain type of nanomaterial on microbial denitrification. Here we show that the toxicity of CuO nanoparticles (NPs) to denitrification in marine sediments is highly affected by the presence of carbon nanotubes (CNTs). It was found that the removal efficiency of total NOX−-N (NO3−-N and NO2−-N) in the presence of CuO NPs was only 62.3%, but it increased to 81.1% when CNTs appeared in this circumstance. Our data revealed that CuO NPs were more easily attached to CNTs rather than cell surface because of the lower energy barrier (3.5 versus 36.2 kT). Further studies confirmed that the presence of CNTs caused the formation of large, incompact, non-uniform dispersed and more negatively charged CuO-CNTs heteroaggregates and thus reduced the nanoparticle internalization by cells, leading to less toxicity to metabolism of carbon source, generation of reduction equivalent and activities of nitrate reductase and nitrite reductase. These results indicate that assessing nanomaterial-induced risks in real circumstances needs to consider the “mixed” effects of nanomaterials.
Ultrasound characterization of the mastoid for detecting middle ear effusion: A preliminary clinical validation
Authors: Chen Chin-Kuo , Fang Jui , Wan Yung-Liang , Tsui Po-Hsiang 
Published: June 2016

AbstractUltrasound detection of middle ear effusion (MEE) is an emerging technique in otolaryngology. This study proposed using ultrasound characterization of the mastoid to noninvasively measure MEE-induced mastoid effusion (ME) as a new strategy for determining the presence of MEE. In total, 53 patients were enrolled (Group I: normal, n = 20; Group II: proven MEE through both otoscopy and tympanometry, n = 15; Group III: patients with MEE having effusions observed during grommet surgery, n = 18). A 2.25-MHz delay-line transducer was used to measure backscattered signals from the mastoid. The Nakagami parameter was estimated using the acquired signals to model the echo amplitude distribution for quantifying changes in the acoustic structures of mastoid air cells. The median Nakagami parameter and interquartile range were 0.35 (0.34–0.37) for Group I, 0.39 (0.37–0.41) for Group II and 0.43 (0.39–0.51) for Group III. The echo amplitude distribution observed for patients with MEE was closer to Rayleigh distribution than that without MEE. Receiver operating characteristic (ROC) curve analysis further revealed that the area under the ROC was 0.88, sensitivity was 72.73%, specificity was 95% and accuracy was 81.13%. The proposed method has considerable potential for noninvasive and comfortable evaluation of MEE.
The structural alteration of gut microbiota in low-birth-weight mice undergoing accelerated postnatal growth
Authors: Wang Jingjing , Tang Huang , Wang Xiaoxin , Zhang Xu , Zhang Chenhong , Zhang Menghui , Zhao Yufeng , Zhao Liping , Shen Jian 
Published: June 2016

AbstractThe transient disruption of gut microbiota in infancy by antibiotics causes adult adiposity in mice. Accelerated postnatal growth (A) leads to a higher risk of adult metabolic syndrome in low birth-weight (LB) humans than in normal birth-weight (NB) individuals, but the underlying mechanism remains unclear. Here, we set up an experiment using LB + A mice, NB + A mice, and control mice with NB and normal postnatal growth. At 24 weeks of age (adulthood), while NB + A animals had a normal body fat content and glucose tolerance compared with controls, LB + A mice exhibited excessive adiposity and glucose intolerance. In infancy, more fecal bacteria implicated in obesity were increased in LB + A pups than in NB + A pups, including Desulfovibrionaceae, Enterorhabdus, and Barnesiella. One bacterium from the Lactobacillus genus, which has been implicated in prevention of adult adiposity, was enhanced only in NB + A pups. Besides, LB + A pups, but not NB + A pups, showed disrupted gut microbiota fermentation activity. After weaning, the fecal microbiota composition of LB + A mice, but not that of NB + A animals, became similar to that of controls by 24 weeks. In infancy, LB + A mice have a more dysbiotic gut microbiome compared to NB + A mice, which might increase their risk of adult metabolic syndrome.
1H-detected solid-state NMR of proteins entrapped in bioinspired silica: a new tool for biomaterials characterization
Authors: Ravera Enrico , Cerofolini Linda , Martelli Tommaso , Louka Alexandra , Fragai Marco , Luchinat Claudio 
Published: June 2016

AbstractProton-detection in solid-state NMR, enabled by high magnetic fields (>18 T) and fast magic angle spinning (>50 kHz), allows for the acquisition of traditional 1H-15N experiments on systems that are too big to be observed in solution. Among those, proteins entrapped in a bioinspired silica matrix are an attractive target that is receiving a large share of attention. We demonstrate that 1H-detected SSNMR provides a novel approach to the rapid assessment of structural integrity in proteins entrapped in bioinspired silica.
Effects of LDL Receptor Modulation on Lymphatic Function
Authors: Milasan Andreea , Dallaire François , Mayer Gaétan , Martel Catherine 
Published: June 2016

AbstractAtherosclerosis is driven by the accumulation of immune cells and cholesterol in the arterial wall. Although recent studies have shown that lymphatic vessels play an important role in macrophage reverse cholesterol transport, the specific underlying mechanisms of this physiological feature remain unknown. In the current report, we sought to better characterize the lymphatic dysfunction that is associated with atherosclerosis by studying the physiological and temporal origins of this impairment. First, we assessed that athero-protected Pcsk9−/− mice exhibited improved collecting lymphatic vessel function throughout age when compared to WT mice for up to six months, while displaying enhanced expression of LDLR on lymphatic endothelial cells. Lymphatic dysfunction was present before the atherosclerotic lesion formation in a mouse model that is predisposed to develop atherosclerosis (Ldlr−/−; hApoB100+/+). This dysfunction was presumably associated with a defect in the collecting lymphatic vessels in a non-specific cholesterol- but LDLR-dependent manner. Treatment with a selective VEGFR-3 agonist rescued this impairment observed early in the onset of this arterial disease. We suggest that LDLR modulation is associated with early atherosclerosis-related lymphatic dysfunction and bring forth a pleiotropic role for PCSK9 in lymphatic function. Our study unveils new potential therapeutic targets for the prevention and treatment of atherosclerosis.
Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-κB Pathway
Authors: Wang Xiantao , Sun Yuhan , Yang Huafeng , Lu Yuanxi , Li Lang 
Published: June 2016

AbstractThis study was designed to investigate the apoptosis induced by oxidized low-density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor κB (NF-κB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions significantly. Decrease of Bcl-2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL-induced cardiomyocyte apoptosis, TLR4 and NF-κB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-κB signaling pathway.
The effect of subarachnoid erythrocyte lysate on brain injury: a preliminary study
Authors: Zhang Zi-Huan , Han Yan-Ling , Wang Chun-Xi , Zhou Chen-Hui , Wu Ling-Yun , Zhang Hua-Sheng , Chen Qiang , Fan Jie-Mei , Zhou Meng-Liang , Hang Chun-Hua 
Published: June 2016

Abundant erythrocytes remain and lyse partially in the subarachnoid space after severe subarachnoid haemorrhage (SAH). But the effect of subarachnoid erythrocyte lysate on brain injury is still not completely clear. In this study, autologous erythrocytes (the non-lysate group) and their lysate (the lysate group) were injected separately into the cistern magna of rabbits to induce a model of experimental SAH, although the control group received isotonic sodium chloride solution instead of erythrocyte solution. Results showed that vasospasm of the basilar artery was observed at 72 h after experimental SAH, but there was no significant difference between the non-lysate group and the lysate group. Brain injury was more severe in the lysate group than in the non-lysate group. Meanwhile, the levels of peroxiredoxin 2 (Prx2), IL-6 and TNF-α in brain cortex and in CSF were significantly higher in the lysate group than those in the non-lysate group. These results demonstrated that brain injury was more likely to be caused by erythrocyte lysate than by intact erythrocytes in subarachnoid space, and inflammation response positively correlated with Prx2 expression might be involved in mechanism of brain injury after SAH.
Rhomboids, signalling and cell biology
Authors: Freeman Matthew 
Published: June 2016

Here, I take a somewhat personal perspective on signalling control, focusing on the rhomboid-like superfamily of proteins that my group has worked on for almost 20 years. As well as describing some of the key and recent advances, I attempt to draw out signalling themes that emerge. One important message is that the genetic and biochemical perspective on signalling has tended to underplay the importance of cell biology. There is clear evidence that signalling pathways exploit the control of intracellular trafficking, protein quality control and degradation and other cell biological phenomena, as important regulatory opportunities.
Treatment of metastatic renal cell carcinoma (mRCC) with CAIX CAR-engineered T-cells–a completed study overview
Authors: Lamers Cor H.J. , Klaver Yarne , Gratama Jan W. , Sleijfer Stefan , Debets Reno 
Published: June 2016

We studied safety and proof of concept of a phase I/II trial with chimeric antigen receptor (CAR) T-cells in patients with metastatic renal cell carcinoma (mRCC). The CAR was based on the G250 mAb that recognized an epitope of carboxy-anhydrase-IX (CAIX). Twelve patients with CAIX+ mRCC were treated in three cohorts with a maximum of 10 daily infusions of 2×107 to 2×109 CAR T-cells. Circulating CAR T-cells were transiently detectable in all patients and maintained antigen-specific immune functions following their isolation post-treatment. Blood cytokine profiles mirrored CAR T-cell presence and in vivo activity. Unfortunately, patients developed anti-CAR T-cell antibodies and cellular immune responses. Moreover, CAR T-cell infusions induced liver enzyme disturbances reaching CTC grades 2–4, which necessitated cessation of treatment in four out of eight patients (cohort 1+2). Examination of liver biopsies revealed T-cell infiltration around bile ducts and CAIX expression on bile duct epithelium, adding to the notion of on-target toxicity. No such toxicities were observed in four patients that were pretreated with G250 mAb (cohort 3). The study was stopped due to the advent of competing treatments before reaching therapeutic or maximum tolerated dose in cohort 3. No clinical responses have been recorded. Despite that, from this trial numerous recommendations for future trials and their immune monitoring could be formulated, such as choice of the target antigen, format and immunogenicity of receptor and how the latter relates to peripheral T-cell persistence.
Crystallizing the function of the magnetosome membrane mineralization protein Mms6
Authors: Staniland Sarah S. , Rawlings Andrea E. 
Published: June 2016

The literature on the magnetosome membrane (MM) protein, magnetosome membrane specific6 (Mms6), is reviewed. Mms6 is native to magnetotactic bacteria (MTB). These bacteria take up iron from solution and biomineralize magnetite nanoparticles within organelles called magnetosomes. Mms6 is a small protein embedded on the interior of the MM and was discovered tightly associated with the formed mineral. It has been the subject of intensive research as it is seen to control the formation of particles both in vivo and in vitro. Here, we compile, review and discuss the research detailing Mms6’s activity within the cell and in a range of chemical in vitro methods where Mms6 has a marked effect on the composition, size and distribution of synthetic particles, with approximately 21 nm in size for solution precipitations and approximately 90 nm for those formed on surfaces. Furthermore, we review and discuss recent work detailing the structure and function of Mms6. From the evidence, we propose a mechanism for its function as a specific magnetite nucleation protein and summaries the key features for this action: namely, self-assembly to display a charged surface for specific iron binding, with the curvature of the surfaces determining the particle size. We suggest these may aid design of biomimetic additives for future green nanoparticle production.
Towards developing algal synthetic biology
Authors: Scaife Mark Aden , Smith Alison Gail 
Published: June 2016

The genetic, physiological and metabolic diversity of microalgae has driven fundamental research into photosynthesis, flagella structure and function, and eukaryotic evolution. Within the last 10 years these organisms have also been investigated as potential biotechnology platforms, for example to produce high value compounds such as long chain polyunsaturated fatty acids, pigments and antioxidants, and for biodiesel precursors, in particular triacylglycerols (TAGs). Transformation protocols, molecular tools and genome sequences are available for a number of model species including the green alga Chlamydomonas reinhardtii and the diatom Phaeodactylum tricornutum, although for both species there are bottlenecks to be overcome to allow rapid and predictable genetic manipulation. One approach to do this would be to apply the principles of synthetic biology to microalgae, namely the cycle of Design-Build-Test, which requires more robust, predictable and high throughput methods. In this mini-review we highlight recent progress in the areas of improving transgene expression, genome editing, identification and design of standard genetic elements (parts), and the use of microfluidics to increase throughput. We suggest that combining these approaches will provide the means to establish algal synthetic biology, and that application of standard parts and workflows will avoid parallel development and capitalize on lessons learned from other systems.
Einfluss von Teamarbeit auf Wohlbefinden und emotionale Erschöpfung von Mitarbeitern in der medizinischen Rehabilitation
Authors: Becker S. , Konrad A. , Zimmermann L. , Müller C. , Tomczyk S. , Reichler L. , Körner M. 
Published: June 2016

Zusammenfassung
Ziel der Studie: Emotionale Erschöpfung und Wohlbefinden von Mitarbeitern sind Indikatoren, welche im Zusammenhang mit der hohen Prävalenz psychischer und psychosomatischer Erkrankungen bei Mitarbeitern im Gesundheitswesen von Bedeutung sind. Teamarbeit kann das Wohlbefinden der Mitarbeiter positiv beeinflussen. Dies ist jedoch im Bereich der Rehabilitation noch unzureichend belegt. Ziel der vorliegenden Studie war es, Aspekte von Teamarbeit als Prädiktoren für Wohlbefinden und emotionale Erschöpfung bei Mitarbeitern in deutschen Rehabilitationskliniken zu untersuchen.
Methodik: Die Daten wurden in insgesamt 10 Rehabilitationskliniken in Südwestdeutschland erhoben, davon wurden die Mitarbeiterfragebogen aus 9 Kliniken (n=306, 70% weiblich, 68% zwischen 40 und 59 Jahre alt) mittels multipler linearer Regression ausgewertet.
Ergebnisse: Die Mitarbeiter berichteten moderate Maße an emotionaler Erschöpfung und hohes Wohlbefinden. Die Ergebnisse der Regressionsanalysen zeigen, dass Zusammenhalt (β=0,27, p<0,001), Teamorganisation (β=0,19, p<0,01) und Alter (β=0,13, p<0,05) der Mitarbeiter einen bedeutsamen Teil der Varianz von Wohlbefinden aufklären konnten (F[3, 244]=19,38, p<0,05). Durch das Kriterium Zusammenhalt (β=− 0.37, p<0,001) konnte die emotionale Erschöpfung der Mitarbeiter bedeutsam vorhergesagt werden (F[1, 244]=39,19, p<0,001).
Schlussfolgerung: Diskutiert werden die Auswirkungen der interpersonellen und strukturellen Aspekte von Teamarbeit, sowie die potentielle Relevanz von Interventionsmaßnahmen zur Verbesserung der Teamarbeit, um eine Steigerung des psychischen Wohlbefindens der Mitarbeiter zu erreichen.
Inhibitory effect of 13 taxane diterpenoids from Chinese yew (Taxus chinensis var. mairei) on the proliferation of HeLa cervical cancer cells
Authors: Liu Hai-Sheng , Gao Yu-Huan , Liu Li-Hong , Liu Wei , Shi Qing-Wen , Dong Mei , Suzuki Toshikazu , Kiyota Hiromasa 
Published: June 2016

Abstract
The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensis var. mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability.
Multiscale subgrid models of large eddy simulation for turbulent flows
Authors: Jiao Jianying , Zhang Ye 
Published: June 2016

Purpose– The purpose of this paper is to propose three modified subgrid-scale (SGS) eddy-viscosity models to improve their original eddy-viscosity models (the Smagorinsky model (SM), the mixed-scale model (MSM), and the wall-adapted local eddy-viscosity model (WALE)) in the simulation of turbulent flows in near-wall region.Design/methodology/approach– The subgrid viscosity is related to the norm of strain rate tensor of the smallest resolved scales, instead of the norm of the resolved strain rate tensor of the large scales.Findings– All the SGS viscosity of the modified eddy-viscosity models (small-large model, modified MSM, and modified WALE) is closer to y+3 behavior than those of the original eddy-viscosity models (SM, MSM, and WALE) near the wall.Originality/value– The norm of strain rate tensor of the smallest scales used in eddy-viscosity models, instead of the norm of strain rate tensor, makes the eddy viscosity in near-wall region approach to zero in a physical sense.
Numerical study of magnetohydrodynamics generalized Couette flow of Eyring-Powell fluid with heat transfer and slip condition
Authors: Ellahi R , Shivanian E , Abbasbandy S , Hayat T. 
Published: June 2016

Purpose
– The purpose of this paper is to study the generalized Couette flow of Eyring-Powell fluid. The paper aims to discuss diverse issues befell for the heat transfer, magnetohydrodynamics and slip.

Design/methodology/approach
– A hybrid technique based on pseudo-spectral collocation is applied for the solution of nonlinear resulting system.

Findings
– Viscous fluid results which are yet not available can be taken as a limiting case of presented problem. The results for the case of Hartmann flow can be obtained as a special case when plate velocity is zero, i.e. pressure gradient induced flow. The results for the zero fluid slip and no thermal slip also become special cases of this work, and the results can be recovered by setting, and to zero. These solutions are valid not only for small but also for large values of all emerging parameters.

Originality/value
– This model is investigated for the first time, as the authors know.