bluuebunny/crossref_metadata_2025_split huggingface dataset:
A gain-of-function ACTC1 3′UTR mutation that introduces a miR-139-5p target site may be associated with a dominant familial atrial septal defect
Authors: Wang Ye , Du Xinwei , Zhou Zaiwei , Jiang Jun , Zhang Zhen , Ye Lincai , Hong Haifa 
Published: May 2016

AbstractThe ostium secundum atrial septal defect (ASDII) is the most common type of congenital heart disease and is characterized by a left to right shunting of oxygenated blood caused by incomplete closure of the septum secundum. We identified a familial form of isolated ASDII that affects four individuals in a family of five and shows autosomal dominant inheritance. By whole genome sequencing, we discovered a new mutation (c.*1784T > C) in the 3′-untranslated region (3′UTR) of ACTC1, which encodes the predominant actin in the embryonic heart. Further analysis demonstrated that the c.*1784T > C mutation results in a new target site for miRNA-139-5p, a microRNA that is involved in cell migration, invasion, and proliferation. Functional analysis demonstrated that the c.*1784T > C mutation specifically downregulates gene expression in a luciferase assay. Additionally, miR-139-5p mimic causes further decrease, whereas miR-139-5p inhibitor can dramatically rescue the decline in gene expression caused by this mutation. These findings suggest that the familial ASDII may be a result of an ACTC1 3′UTR gain-of-function mutation caused by the introduction of a new miR-139-5p target site. Our results provide the first evidence of a pathogenic mutation in the ACTC1 3′UTR that may be associated with familial isolated ASDII.
Coupled grain boundary motion in aluminium: the effect of structural multiplicity
Authors: Cheng Kuiyu , Zhang Liang , Lu Cheng , Tieu Kiet 
Published: May 2016

AbstractThe shear-induced coupled grain boundary motion plays an important role in the deformation of nanocrystalline (NC) materials. It has been known that the atomic structure of the grain boundary (GB) is not necessarily unique for a given set of misorientation and inclination of the boundary plane. However, the effect of the structural multiplicity of the GB on its coupled motion has not been reported. In the present study we investigated the structural multiplicity of the symmetric tilt Σ5(310) boundary in aluminium and its influence on the GB behaviour at a temperature range of 300 K–600 K using molecular dynamic simulations. Two starting atomic configurations were adopted in the simulations which resulted in three different GB structures at different temperatures. Under the applied shear deformation each GB structure exhibited its unique GB behaviour. A dual GB behaviour, namely the transformation of one GB behaviour to another during deformation, was observed for the second starting configuration at a temperature of 500 K. The atomistic mechanisms responsible for these behaviour were analysed in detail. The result of this study implicates a strong relationship between GB structures and their behaviour and provides a further information of the grain boundary mediated plasticity in nanocrystalline materials.
Vacancy Structures and Melting Behavior in Rock-Salt GeSbTe
Authors: Zhang Bin , Wang Xue-Peng , Shen Zhen-Ju , Li Xian-Bin , Wang Chuan-Shou , Chen Yong-Jin , Li Ji-Xue , Zhang Jin-Xing , Zhang Ze , Zhang Sheng-Bai , Han Xiao-Dong 
Published: May 2016

AbstractGe-Sb-Te alloys have been widely used in optical/electrical memory storage. Because of the extremely fast crystalline-amorphous transition, they are also expected to play a vital role in next generation nonvolatile microelectronic memory devices. However, the distribution and structural properties of vacancies have been one of the key issues in determining the speed of melting (or amorphization), phase-stability and heat-dissipation of rock-salt GeSbTe, which is crucial for its technological breakthrough in memory devices. Using spherical aberration-aberration corrected scanning transmission electron microscopy and atomic scale energy-dispersive X-ray mapping, we observe a new rock-salt structure with high-degree vacancy ordering (or layered-like ordering) at an elevated temperature, which is a result of phase transition from the rock-salt phase with randomly distributed vacancies. First-principles calculations reveal that the phase transition is an energetically favored process. Moreover, molecular dynamics studies suggest that the melting of the cubic rock-salt phases is initiated at the vacancies, which propagate to nearby regions. The observation of multi-rock-salt phases suggests another route for multi-level data storage using GeSbTe.
Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer
Authors: Werner Simone , Chen Hongda , Butt Julia , Michel Angelika , Knebel Phillip , Holleczek Bernd , Zörnig Inka , Eichmüller Stefan B. , Jäger Dirk , Pawlita Michael , Waterboer Tim , Brenner Hermann 
Published: May 2016

AbstractAutoantibodies against tumor-associated antigens (TAAs) have been suggested as biomarkers for early detection of gastric cancer. However, studies that systematically assess the diagnostic performance of a large number of autoantibodies are rare. Here, we used bead-based multiplex serology to simultaneously measure autoantibody responses against 64 candidate TAAs in serum samples from 329 gastric cancer patients, 321 healthy controls and 124 participants with other diseases of the upper digestive tract. At 98% specificity, sensitivities for the 64 tested autoantibodies ranged from 0–12% in the training set and a combination of autoantibodies against five TAAs (MAGEA4 + CTAG1 + TP53 + ERBB2_C + SDCCAG8) was able to detect 32% of the gastric cancer patients at a specificity of 87% in the validation set. Sensitivities for early and late stage gastric cancers were similar, while chronic atrophic gastritis, a precursor lesion of gastric cancer, was not detectable. However, the 5-marker combination also detected 26% of the esophageal cancer patients. In conclusion, the tested autoantibodies and combinations alone did not reach sufficient sensitivity for gastric cancer screening. Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers.
Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases
Authors: Narita Tomomi , Naganuma Tatsuro , Sase Yurie , Kihara Akio 
Published: May 2016

AbstractTransport of dietary lipids into small-intestinal epithelial cells is pathologically and nutritionally important. However, lipid uptake remains an almost unexplored research area. Although we know that long-chain bases (LCBs), constituents of sphingolipids, can enter into cells efficiently, the molecular mechanism of LCB uptake is completely unclear. Here, we found that the yeast acyl-CoA synthetases (ACSs) Faa1 and Faa4 are redundantly involved in LCB uptake. In addition to fatty acid-activating activity, transporter activity toward long-chain fatty acids (LCFAs) has been suggested for ACSs. Both LCB and LCFA transports were largely impaired in faa1Δ faa4Δ cells. Furthermore, LCB and LCFA uptakes were mutually competitive. However, the energy dependency was different for their transports. Sodium azide/2-deoxy-D-glucose treatment inhibited import of LCFA but not that of LCB. Furthermore, the ATP-AMP motif mutation FAA1 S271A largely impaired the metabolic activity and LCFA uptake, while leaving LCB import unaffected. These results indicate that only LCFA transport requires ATP. Since ACSs do not metabolize LCBs as substrates, Faa1 and Faa4 are likely directly involved in LCB transport. Furthermore, we revealed that ACSs are also involved in LCB transport in mammalian cells. Thus, our findings provide strong support for the hypothesis that ACSs directly transport LCFAs.
Dynamic cutaneous information is sufficient for precise curvature discrimination
Authors: Cheeseman Jacob R. , Norman J. Farley , Kappers Astrid M. L. 
Published: May 2016

AbstractOur tactual perceptual experiences occur when we interact, actively and passively, with environmental objects and surfaces. Previous research has demonstrated that active manual exploration often enhances the tactual perception of object shape. Nevertheless, the factors that contribute to this enhancement are not well understood. The present study evaluated the ability of 28 younger (mean age was 23.1 years) and older adults (mean age was 71.4 years) to discriminate curved surfaces by actively feeling objects with a single index finger and by passively feeling objects that moved relative to a restrained finger. While dynamic cutaneous stimulation was therefore present in both conditions, active exploratory movements only occurred in one. The results indicated that there was a significant and large effect of age, such that the older participants’ thresholds were 43.8 percent higher than those of the younger participants. Despite the overall adverse effect of age, the pattern of results across the active and passive touch conditions was identical. For both age groups, the curvature discrimination thresholds obtained for passive touch were significantly lower than those that occurred during active touch. Curvature discrimination performance was therefore best in the current study when dynamic cutaneous stimulation occurred in the absence of active movement.
Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal
Authors: Risso Davide S. , Mezzavilla Massimo , Pagani Luca , Robino Antonietta , Morini Gabriella , Tofanelli Sergio , Carrai Maura , Campa Daniele , Barale Roberto , Caradonna Fabio , Gasparini Paolo , Luiselli Donata , Wooding Stephen , Drayna Dennis 
Published: May 2016

AbstractThe ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.
Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data
Authors: Sariaslan A , Fazel S , D'Onofrio B M , Långström N , Larsson H , Bergen S E , Kuja-Halkola R , Lichtenstein P 
Published: May 2016

AbstractNeighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60–71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20–0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R2=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs.
Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
Authors: Hüttenrauch M , Brauß A , Kurdakova A , Borgers H , Klinker F , Liebetanz D , Salinas-Riester G , Wiltfang J , Klafki H W , Wirths O 
Published: May 2016

AbstractThe evidence for a protective role of physical activity on the risk and progression of Alzheimer’s disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.
HPA-axis function and grey matter volume reductions: imaging the diathesis-stress model in individuals at ultra-high risk of psychosis
Authors: Valli I , Crossley N A , Day F , Stone J , Tognin S , Mondelli V , Howes O , Valmaggia L , Pariante C , McGuire P 
Published: May 2016

AbstractThe onset of psychosis is thought to involve interactions between environmental stressors and the brain, with cortisol as a putative mediator. We examined the relationship between the cortisol stress response and brain structure in subjects at ultra-high risk (UHR) for psychosis. Waking salivary cortisol was measured in 22 individuals at UHR for psychosis and 17 healthy controls. Grey matter volume was assessed using magnetic resonance imaging at 3 T. The relationship between the stress response and grey matter volume was investigated using voxel-based analyses. Our predictions of the topography of cortisol action as a structural brain modulator were informed by measures of brain glucocorticoid and mineralcorticoid receptor distribution obtained from the multimodal neuroanatomical and genetic Allen Brain Atlas. Across all subjects, reduced responsivity of the hypothalamus–pituitary–adrenal (HPA) axis was correlated with smaller grey matter volumes in the frontal, parietal and temporal cortex and in the hippocampus. This relationship was particularly marked in the UHR subjects in the right prefrontal, left parahippocampal/fusiform and parietal cortices. The subgroup that subsequently developed psychosis showed a significant blunting of HPA stress response, observed at trend level also in the whole UHR sample. Altered responses to stress in people at high risk of psychosis are related to reductions in grey matter volume in areas implicated in the vulnerability to psychotic disorders. These areas may represent the neural components of a stress vulnerability model.
High‐performance fully transparent Al–Sn–Zn–O thin‐film transistors using double‐channel structures
Authors: Cong Yingying , Han Dedong , Dong Junchen , Yu Wen , Zhang Xiaomi , Cui Guodong , Zhang Xing , Zhang Shengdong , Wang Yi 
Published: May 2016

We successfully fabricated the fully transparent Al–Sn–Zn–O thin‐film transistors (ATZO TFTs) on glass by RF magnetron sputtering, and then the electrical performances of the ATZO TFTs are optimized with double‐channel structures. The double‐channel structures are formed by using bilayer ATZO films fabricated successively with different oxygen partial pressure in the sputtering process. The operation mechanism for double‐channel structures were clarified. Owing to the double‐channel structure, the ATZO TFT demonstrates excellent electrical performances, including a high ON/OFF current ratio (Ion/Ioff) of 1.1 × 108, a steep threshold swing SS of 266.3 mV/decade, a superior saturation mobility μsat of 134.1 cm2/Vs, and a threshold voltage VT of 1.2 V.
Utilisation of real‐scale renewable energy test facility for validation of generic wind turbine and wind power plant controller models
Authors: Zeni Lorenzo , Gevorgian Vahan , Wallen Robb , Bech John , Sørensen Poul Ejnar , Hesselbæk Bo 
Published: May 2016

This article presents an example of application of a modern test facility conceived for experiments regarding the integration of renewable energy in the power system. The capabilities of the test facility are used to validate dynamic simulation models of wind power plants and their controllers. The models are based on standard and generic blocks. The successful validation of events related to the control of active power (control phenomena in <10 Hz range, including frequency control and power oscillation damping) is described, demonstrating the capabilities of the test facility and drawing the track for future work and improvements.
Evaluation of Perfusion Quantification Methods with Ultrasound Contrast Agents in a Machine-Perfused Pig Liver
Authors: Averkiou Michalakis , Keravnou Christina , Izamis Maria , Leen Edward 
Published: May 2016

Abstract
Purpose To evaluate dynamic contrast-enhanced ultrasound (DCEUS) as a tool for measuring blood flow in the macro- and microcirculation of an ex-vivo machine-perfused pig liver and to confirm the ability of DCEUS to accurately detect induced flow rate changes so that it could then be used clinically for monitoring flow changes in liver tumors.
Materials and Methods Bolus injections of contrast agents in the hepatic artery (HA) and portal vein (PV) were administered to 3 machine-perfused pig livers. Flow changes were induced by the pump of the machine perfusion system. The induced flow rates were of clinical relevance (150 – 400 ml/min for HA and 400 – 1400 ml/min for PV). Quantification parameters from time-intensity curves [rise time (RT), mean transit time (MTT), area under the curve (AUC) and peak intensity (PI)] were extracted in order to evaluate whether the induced flow changes were reflected in these parameters.
Results A linear relationship between the image intensity and the microbubble concentration was confirmed first, while time parameters (RT and MMT) were found to be independent of concentration. The induced flow changes which propagated from the larger vessels to the parenchyma were reflected in the quantification parameters. Specifically, RT, MTT and AUC correlated with flow rate changes.
Conclusion Machine-perfused pig liver is an excellent test bed for DCEUS quantification approaches for the study of the hepatic vascular networks. DCEUS quantification parameters (RT, MTT, and AUC) can measure relative flow changes of about 20 % and above in the liver vasculature. DCEUS quantification is a promising tool for real-time monitoring of the vascular network of tumors.
Adding Liver Stiffness Measurement to the Routine Evaluation of Hepatocellular Carcinoma Resectability Can Optimize Clinical Outcome
Authors: Cucchetti Alessandro , Cescon Matteo , Colecchia Antonio , Neri Flavia , Cappelli Alberta , Ravaioli Matteo , Mazzotti Federico , Ercolani Giorgio , Festi Davide , Pinna Antonio 
Published: May 2016

Abstract
Purpose Liver stiffness (LS) has been shown to be of use in chronic liver disease patients but its utility in surgical judgment still needs to be proven. A decision-making approach was applied to evaluate whether LS measurement before surgery of hepatocellular carcinoma (HCC) can be useful in avoiding post-hepatectomy liver failure (PHLF).
Materials and Methods Decision curve analysis (DCA) was applied to 202 HCC patients (2008 – 14) with LS measurement prior to hepatectomy to verify whether the occurrence of PHLF grades B/C should be reduced through a decision-making approach with LS.
Results Within 90 days of surgery, 4 patients died (2 %) and grades B/C PHLF occurred in 29.7 % of cases. Ascites and/or pleural effusion, treatable with medical therapy, were the most frequent complications. DCA showed that using the “expected utility theory” LS measurement can reduce up to 39 % of cases of PHLF without the exclusion of any patient from surgery that duly undergoes an uncomplicated postoperative course. LS measurement does not add any information to normal clinical judgment for patients with a low (< 10 %) risk of PHLF.
Conclusion LS measurement can determine a reduction of PHLF under “expected utility theory” fulfilment. However, the degree of PHLF can be minor and “risk seeking” individuals can accept such a risk on the basis of surgical benefits.
What constitutes appropriate peer review for interdisciplinary research?
Authors: Bammer Gabriele 
Published: May 2016

AbstractHow can interdisciplinary research proposals be more effectively assessed through peer review? A key issue is to characterize what constitutes appropriate peer review for interdisciplinary research. This is approached by considering four key elements on which evaluations of funding proposals are based: (1) the significance of the topic, (2) the importance and tractability of the research question, (3) the appropriateness of the methods and (4) the competence of the applicants, based on track record. Two major differences between disciplinary and interdisciplinary research emerge: (1) the unknowns that form the basis of research questions and (2) the methods employed. For peer review of interdisciplinary research proposals to become more effective, agreed criteria for assessment by peer review are required and this will only occur if interdisciplinarity is “organized” through colleges of peers and professional associations. This article is published as part of a collection on interdisciplinarity.