bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Sorting of Pure Cell Populations Enables Unambiguous Genetic Analysis of Heterogeneous Formalin-Fixed Paraffin-Embedded Tumors by Next Generation Sequencing
Authors: Bolognesi Chiara , Forcato Claudio , Buson Genny , Fontana Francesca , Mangano Chiara , Doffini Anna , Sero Valeria , Lanzellotto Rossana , Signorini Giulio , Calanca Alex , Sergio Maximilian , Romano Rita , Gianni Stefano , Medoro Gianni , Giorgini Giuseppe , Morreau Hans , Barberis Massimo , Corver Willem E. , Manaresi Nicolò 
Published: February 2016

AbstractPrecision medicine in oncology requires an accurate characterization of a tumor molecular profile for patient stratification. Though targeted deep sequencing is an effective tool to detect the presence of somatic sequence variants, a significant number of patient specimens do not meet the requirements needed for routine clinical application. Analysis is hindered by contamination of normal cells and inherent tumor heterogeneity, compounded with challenges of dealing with minute amounts of tissue and DNA damages common in formalin-fixed paraffin-embedded (FFPE) specimens. Here we present an innovative workflow using DEPArray™ system, a microchip-based digital sorter to achieve 100%-pure, homogenous subpopulations of cells from FFPE samples. Cells are distinguished by fluorescently labeled antibodies and DNA content. The ability to address tumor heterogeneity enables unambiguous determination of true-positive sequence variants, loss-of-heterozygosity as well as copy number variants. The proposed strategy overcomes the inherent trade-offs made between sensitivity and specificity in detecting genetic variants from a mixed population, thus rescuing for analysis even the smaller clinical samples with low tumor cellularity.
Task-Specific Balance Training Improves the Sensory Organisation of Balance Control in Children with Developmental Coordination Disorder: A Randomised Controlled Trial
Authors: Fong Shirley S.M. , Guo X. , Liu Karen P.Y. , Ki W.Y. , Louie Lobo H.T. , Chung Raymond C.K. , Macfarlane Duncan J. 
Published: February 2016

AbstractSensory organisation of balance control is compromised in children with developmental coordination disorder (DCD). A randomised controlled trial involving 88 children with DCD was conducted to evaluate the efficacy of a task-specific balance training (functional-movement training, FMT) programme in improving balance deficits in a DCD population. The DCD participants were randomly assigned to either a FMT group or a control group. The FMT group received two training sessions/ week for 3 months. Measurements of the participants’ sensory organisation (somatosensory, vestibular and visual ratios), balance and motor proficiency (Movement Assessment Battery for Children, MABC scores) and center of pressure sway velocity (Unilateral Stance Test, UST scores) were taken at baseline, immediately after FMT and 3 months after FMT. The FMT group showed greater improvements than the controls in somatosensory ratio at 3 and 6 months (all P < 0.001), but the within-group changes were not significant (P > 0.05). The results of both the MABC and the UST also indicated that the balance performance of the FMT group was significantly better than that of the control group at 3 and 6 months (all P < 0.05). Task-specific balance training was found to marginally improve the somatosensory function and somewhat improve the balance performance of children with DCD.
Tackling amyloidogenesis in Alzheimer’s disease with A2V variants of Amyloid-β
Authors: Di Fede Giuseppe , Catania Marcella , Maderna Emanuela , Morbin Michela , Moda Fabio , Colombo Laura , Rossi Alessandro , Cagnotto Alfredo , Virgilio Tommaso , Palamara Luisa , Ruggerone Margherita , Giaccone Giorgio , Campagnani Ilaria , Costanza Massimo , Pedotti Rosetta , Salvalaglio Matteo , Salmona Mario , Tagliavini Fabrizio 
Published: February 2016

AbstractWe developed a novel therapeutic strategy for Alzheimer’s disease (AD) exploiting the properties of a natural variant of Amyloid-β (Aβ) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Aβ1-6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Aβ1-6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Aβ toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Aβ1-6A2VTAT(D) inhibits Aβ aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AβA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Aβ1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Aβ production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics.
A genome-wide search for epigenetically regulated genes in zebra finch using MethylCap-seq and RNA-seq
Authors: Steyaert Sandra , Diddens Jolien , Galle Jeroen , De Meester Ellen , De Keulenaer Sarah , Bakker Antje , Sohnius-Wilhelmi Nina , Frankl-Vilches Carolina , Van der Linden Annemie , Van Criekinge Wim , Vanden Berghe Wim , De Meyer Tim 
Published: February 2016

AbstractLearning and memory formation are known to require dynamic CpG (de)methylation and gene expression changes. Here, we aimed at establishing a genome-wide DNA methylation map of the zebra finch genome, a model organism in neuroscience, as well as identifying putatively epigenetically regulated genes. RNA- and MethylCap-seq experiments were performed on two zebra finch cell lines in presence or absence of 5-aza-2′-deoxycytidine induced demethylation. First, the MethylCap-seq methodology was validated in zebra finch by comparison with RRBS-generated data. To assess the influence of (variable) methylation on gene expression, RNA-seq experiments were performed as well. Comparison of RNA-seq and MethylCap-seq results showed that at least 357 of the 3,457 AZA-upregulated genes are putatively regulated by methylation in the promoter region, for which a pathway analysis showed remarkable enrichment for neurological networks. A subset of genes was validated using Exon Arrays, quantitative RT-PCR and CpG pyrosequencing on bisulfite-treated samples. To our knowledge, this study provides the first genome-wide DNA methylation map of the zebra finch genome as well as a comprehensive set of genes of which transcription is under putative methylation control.
Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster
Authors: Yang Yingying , Su Zhongjing , Song Xuhong , Liang Bin , Zeng Fanxing , Chang Xiaolan , Huang Dongyang 
Published: February 2016

AbstractThe human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene-duplication events. We previously demonstrated that a head-to-head natural antisense transcript (NAT) of DHRS4, denoted DHRS4-AS1, regulates all three genes of the DHRS4 gene cluster. However, it is puzzling that DHRS4L2 and DHRS4L1 did not evolve their own specific NATs to regulate themselves, as it seems both have retained sequences highly homologous to DHRS4-AS1. In a search of the DHRS4-AS1 region for nearby enhancers, we identified an enhancer located 13.8 kb downstream of the DHRS4-AS1 transcriptional start site. We further showed, by using a chromosome conformation capture (3C) assay, that this enhancer is capable of physically interacting with the DHRS4-AS1 promoter through chromosomal looping. The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP. Moreover, the distributions of activating acetyl-H3 and H3K4me3 modifications were found to be greater at the DHRS4-AS1 promoter than at the homologous duplicated regions. We propose that AS1eRNA-driven DNA looping and activating histone modifications promote the expression of DHRS4-AS1 to economically control the DHRS4 gene cluster.
Self-sacrifice Template Formation of Hollow Hetero-Ni7S6/Co3S4 Nanoboxes with Intriguing Pseudo-capacitance for High-performance Electrochemical Capacitors
Authors: Hua Hui , Liu Sijia , Chen Zhiyi , Bao Ruiqi , Shi Yaoyao , Hou Linrui , Pang Gang , Hui Kwun Nam , Zhang Xiaogang , Yuan Changzhou 
Published: February 2016

AbstractHerein, we report a simple yet efficient self-sacrifice template protocol to smartly fabricate hollow hetero-Ni7S6/Co3S4 nanoboxes (Ni-Co-S NBs). Uniform nickel cobalt carbonate nanocubes are first synthesized as the precursor via solvothermal strategy, and subsequently chemically sulfidized into hollow heter-Ni-Co-S NBs through anion-exchange process. When evaluated as electrode for electrochemical capacitors (ECs), the resultant hetero-Ni-Co-S NBs visually exhibit attractive pesudo-capacitance in KOH just after continuously cyclic voltammetry (CV) scanning for 100 cycles. New insights into the underlying energy-storage mechanism of the hollow hetero-Ni-Co-S electrode, based on physicochemical characterizations and electrochemical evaluation, are first put forward that the electrochemically induced phase transformation gradually occurrs during CV sweep from the hetero-Ni-Co-S to bi-component-active NiOOH and CoOOH, which are the intrinsic charge-storage phases for the appealing Faradaic capacitance (~677 F g−1 at 4 A g−1) of hollow Ni-Co-S NBs at high rates after cycling. When further coupled with negative activated carbon (AC), the AC//hetero-Ni-Co-S asymmetric device with extended electrochemical window of 1.5 V demonstrates high specific energy density of ~31 Wh kg−1. Of significance, we strongly envision that hollow design concept and new findings here hold great promise for enriching synthetic methodologies, and electrochemistry of complex metal sulfides for next-generation ECs.
Characterization of a newly isolated strain Pseudomonas sp. C27 for sulfide oxidation: Reaction kinetics and stoichiometry
Authors: Xu Xi-Jun , Chen Chuan , Guo Hong-liang , Wang Ai-jie , Ren Nan-qi , Lee Duu-Jong 
Published: February 2016

AbstractSulfide biooxidation by the novel sulfide-oxidizing bacteria Pseudomonas sp. C27, which could perform autotrophic and heterotrophic denitrification in mixotrophic medium, was studied in batch and continuous systems. Pseudomonas sp. C27 was able to oxidize sulfide at concentrations as high as 17.66 mM. Sulfide biooxidation occurred in two distinct stages, one resulting in the formation of sulfur with nitrate reduction to nitrite, followed by thiosulfate formation with nitrite reduction to N2. The composition of end-products was greatly impacted by the ratio of sulfide to nitrate initial concentrations. At a ratio of 0.23, thiosulfate represented 100% of the reaction products, while only 30% with a ratio of 1.17. In the continuous bioreactor, complete removal of sulfide was observed at sulfide concentration as high as 9.38 mM. Overall sulfide removal efficiency decreased continuously upon further increases in influent sulfide concentrations. Based on the experimental data kinetic parameter values were determined. The value of maximum specific growth rate, half saturation constant, decay coefficient, maintenance coefficient and yield were to be 0.11 h−1, 0.68 mM sulfide, 0.11 h−1, 0.21 mg sulfide/mg biomass h and 0.43 mg biomass/mg sulfide, respectively, which were close to or comparable with those reported in literature by other researches.
Oxidative elemental cycling under the low O2 Eoarchean atmosphere
Authors: Frei Robert , Crowe Sean A. , Bau Michael , Polat Ali , Fowle David A. , Døssing Lasse N. 
Published: February 2016

AbstractThe Great Oxidation Event signals the first large-scale oxygenation of the atmosphere roughly 2.4 Gyr ago. Geochemical signals diagnostic of oxidative weathering, however, extend as far back as 3.3–2.9 Gyr ago. 3.8–3.7 Gyr old rocks from Isua, Greenland stand as a deep time outpost, recording information on Earth’s earliest surface chemistry and the low oxygen primordial biosphere. Here we find fractionated Cr isotopes, relative to the igneous silicate Earth reservoir, in metamorphosed banded iron formations (BIFs) from Isua that indicate oxidative Cr cycling 3.8–3.7 Gyr ago. Elevated U/Th ratios in these BIFs relative to the contemporary crust, also signal oxidative mobilization of U. We suggest that reactive oxygen species were present in the Eoarchean surface environment, under a very low oxygen atmosphere, inducing oxidative elemental cycling during the deposition of the Isua BIFs and possibly supporting early aerobic biology.
Chemotyping the distribution of vitamin D metabolites in human serum
Authors: Müller Miriam J. , Stokes Caroline S. , Lammert Frank , Volmer Dietrich A. 
Published: February 2016

AbstractMost studies examining the relationships between vitamin D and disease or health focus on the main 25-hydroxyvitamin D3 (25(OH)D3) metabolite, thus potentially overlooking contributions and dynamic effects of other vitamin D metabolites, the crucial roles of several of which have been previously demonstrated. The ideal assay would determine all relevant high and low-abundant vitamin D species simultaneously. We describe a sensitive quantitative assay for determining the chemotypes of vitamin D metabolites from serum after derivatisation and ultra-high performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-ESI-MS/MS). We performed a validation according to the ‘FDA Guidance for Industry Bioanalytical Method Validation’. The proof-of-concept of the method was then demonstrated by following the metabolite concentrations in patients with chronic liver diseases (CLD) during the course of a vitamin D supplementation study. The new quantitative profiling assay provided highly sensitive, precise and accurate chemotypes of the vitamin D metabolic process rather than the usually determined 25(OH)D3 concentrations.
A Mendelian randomization study of testosterone and cognition in men
Authors: Zhao Jie V. , Lam Tai Hing , Jiang Chaoqiang , Cherny Stacey S. , Liu Bin , Cheng Kar Keung , Zhang Weisen , Leung Gabriel M. , Schooling C Mary 
Published: February 2016

AbstractTestosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (−0.02 per nmol/L testosterone, 95% confidence interval (CI) −0.06–0.02) or MMSE score (0.06, 95% CI −0.002–0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men.
Dried plum diet protects from bone loss caused by ionizing radiation
Authors: Schreurs A.-S. , Shirazi-Fard Y. , Shahnazari M. , Alwood J. S. , Truong T. A. , Tahimic C. G. T. , Limoli C. L. , Turner N. D. , Halloran B. , Globus R. K. 
Published: February 2016

AbstractBone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.
Majorana bound states from exceptional points in non-topological superconductors
Authors: San-Jose Pablo , Cayao Jorge , Prada Elsa , Aguado Ramón 
Published: February 2016

AbstractRecent experimental efforts towards the detection of Majorana bound states have focused on creating the conditions for topological superconductivity. Here we demonstrate an alternative route, which achieves fully localised zero-energy Majorana bound states when a topologically trivial superconductor is strongly coupled to a helical normal region. Such a junction can be experimentally realised by e.g. proximitizing a finite section of a nanowire with spin-orbit coupling and combining electrostatic depletion and a Zeeman field to drive the non-proximitized (normal) portion into a helical phase. Majorana zero modes emerge in such an open system without fine-tuning as a result of charge-conjugation symmetry and can be ultimately linked to the existence of ‘exceptional points’ (EPs) in parameter space, where two quasibound Andreev levels bifurcate into two quasibound Majorana zero modes. After the EP, one of the latter becomes non-decaying as the junction approaches perfect Andreev reflection, thus resulting in a Majorana dark state (MDS) localised at the NS junction. We show that MDSs exhibit the full range of properties associated to conventional closed-system Majorana bound states (zero-energy, self-conjugation, 4π-Josephson effect and non-Abelian braiding statistics), while not requiring topological superconductivity.
Exploring structural phase transitions of ion crystals
Authors: Yan L. L. , Wan W. , Chen L. , Zhou F. , Gong S. J. , Tong X. , Feng M. 
Published: February 2016

AbstractPhase transitions have been a research focus in many-body physics over past decades. Cold ions, under strong Coulomb repulsion, provide a repealing paradigm of exploring phase transitions in stable confinement by electromagnetic field. We demonstrate various conformations of up to sixteen laser-cooled 40Ca+ ion crystals in a home-built surface-electrode trap, where besides the usually mentioned structural phase transition from the linear to the zigzag, two additional phase transitions to more complicated two-dimensional configurations are identified. The experimental observation agrees well with the numerical simulation. Heating due to micromotion of the ions is analysed by comparison of the numerical simulation with the experimental observation. Our investigation implies very rich and complicated many-body behaviour in the trapped-ion systems and provides effective mechanism for further exploring quantum phase transitions and quantum information processing with ultracold trapped ions.
Prion infection impairs lysosomal degradation capacity by interfering with rab7 membrane attachment in neuronal cells
Authors: Shim Su Yeon , Karri Srinivasarao , Law Sampson , Schatzl Hermann M. , Gilch Sabine 
Published: February 2016

AbstractPrions are proteinaceous infectious particles which cause fatal neurodegenerative disorders in humans and animals. They consist of a mostly β-sheeted aggregated isoform (PrPSc) of the cellular prion protein (PrPc). Prions replicate autocatalytically in neurons and other cell types by inducing conformational conversion of PrPc into PrPSc. Within neurons, PrPSc accumulates at the plasma membrane and in vesicles of the endocytic pathway. To better understand the mechanisms underlying neuronal dysfunction and death it is critical to know the impact of PrPSc accumulation on cellular pathways. We have investigated the effects of prion infection on endo-lysosomal transport. Our study demonstrates that prion infection interferes with rab7 membrane association. Consequently, lysosomal maturation and degradation are impaired. Our findings indicate a mechanism induced by prion infection that supports stable prion replication. We suggest modulation of endo-lysosomal vesicle trafficking and enhancement of lysosomal maturation as novel targets for the treatment of prion diseases.
Preparation of multi‐walled carbon nanotubes/SiO2 core–shell nanocomposites by a two‐step Stöber process
Authors: Sun Chang , Sun Kangning 
Published: February 2016

The surface modification and functionalisation of multi‐walled carbon nanotubes (MWNTs) could provide enhanced properties to MWNTs for highly specific applications which often require solubilisation and dispersion, promotion of functionality, biocompatibility or lower toxicity of MWNTs. Herein, a novel nanocomposite consisting of MWNTs as a core and amorphous silica (SiO2) as a shell is developed. First, the functionalisation of MWNTs with carboxylic functional group (MWNTs‐COOH) was obtained via oxidation using the concentrated sulphuric acid/nitric acid mixture (3:1 v/v) treatment. Second, a silica uniform layer was grown on MWNTs‐COOH by a two‐step Stöber process. The core–shell nanostructure is characterised by Fourier‐transform infrared spectroscopy, X‐ray powder diffraction, transmission electron microscopy, and energy dispersive spectrometer. Experimental results show that a SiO2 shell was uniformly coated on the surface of MWNTs with a thickness of 5–10 nm. The results can have important implications for the preparation of carbon nanotube core–shell nanocomposites in general.
Helicity is the only integral invariant of volume-preserving transformations
Authors: Enciso Alberto , Peralta-Salas Daniel , de Lizaur Francisco Torres 
Published: February 2016

Significance
Helicity is a remarkable conserved quantity that is fundamental to all the natural phenomena described by a vector field whose evolution is given by volume-preserving transformations. This is the case of the vorticity of an inviscid fluid flow or of the magnetic field of a conducting plasma. The topological nature of the helicity was unveiled by Moffatt, but its relevance goes well beyond that of being a new conservation law. Indeed, the helicity defines an integral invariant under any kind of volume-preserving diffeomorphisms. A well-known open problem is whether any integral invariants exist other than the helicity. We answer this question by showing that, under some mild technical assumptions, the helicity is the only integral invariant.