bluuebunny/crossref_metadata_2025_split huggingface dataset:
The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization
Authors: Alam Mohammad Tauqeer , Olin-Sandoval Viridiana , Stincone Anna , Keller Markus A. , Zelezniak Aleksej , Luisi Ben F. , Ralser Markus 
Published: July 2017

AbstractMetabolites can inhibit the enzymes that generate them. To explore the general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century of experimentation and generated a genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects the majority of biochemical processes, and is executed by a structured network whose topological organization is reflecting chemical similarities that exist between metabolites. Most inhibitory interactions are competitive, emerge in the close neighbourhood of the inhibited enzymes, and result from structural similarities between substrate and inhibitors. Structural constraints also explain one-third of allosteric inhibitors, a finding rationalized by crystallographic analysis of allosterically inhibited L-lactate dehydrogenase. Our findings suggest that the primary cause of metabolic enzyme inhibition is not the evolution of regulatory metabolite–enzyme interactions, but a finite structural diversity prevalent within the metabolome. In eukaryotes, compartmentalization minimizes inevitable enzyme inhibition and alleviates constraints that self-inhibition places on metabolism.
Global mismatch between fishing dependency and larval supply from marine reserves
Authors: Andrello Marco , Guilhaumon François , Albouy Camille , Parravicini Valeriano , Scholtens Joeri , Verley Philippe , Barange Manuel , Sumaila U. Rashid , Manel Stéphanie , Mouillot David 
Published: July 2017

AbstractMarine reserves are viewed as flagship tools to protect exploited species and to contribute to the effective management of coastal fisheries. Yet, the extent to which marine reserves are globally interconnected and able to effectively seed areas, where fisheries are most critical for food and livelihood security is largely unknown. Using a hydrodynamic model of larval dispersal, we predict that most marine reserves are not interconnected by currents and that their potential benefits to fishing areas are presently limited, since countries with high dependency on coastal fisheries receive very little larval supply from marine reserves. This global mismatch could be reversed, however, by placing new marine reserves in areas sufficiently remote to minimize social and economic costs but sufficiently connected through sea currents to seed the most exploited fisheries and endangered ecosystems.
SRGN-TGFβ2 regulatory loop confers invasion and metastasis in triple-negative breast cancer
Authors: Zhang Z , Deng Y , Zheng G , Jia X , Xiong Y , Luo K , Qiu Q , Qiu Ni , Yin J , Lu M , Liu H , Gu Y , He Z 
Published: July 2017

AbstractPatients with triple-negative breast cancers (TNBC) are at a high risk for a recurrent or metastatic disease, and the molecular mechanisms associated with this risk are unclear. Proteoglycan serglycin (SRGN) proteins are involved in tumor metastasis, but their role in TNBC has not yet been elucidated. This study investigates the SRGN gene expression and how it regulates TGFβ2 and the downstream signaling of TGFβ2 in TNBC cells and tissues. Our results show that SRGN mRNA and protein expression levels were significantly higher in TNBC cell lines and tumor tissues than that in non-TNBC cells and tissues. We inhibited SRGN expression and protein secretion using shRNA and we observed this inhibited the invasive motility of TNBC cancer cells in vitro and metastasis of TNBC cancer cells in vivo. SRGN protein treatment increased the expression and secretion of transforming growth factor-β2 (TGFβ2) by activating CD44/CREB1 signaling and promoted epithelial-to-mesenchymal transition in TNBC cells. Moreover, TGFβ2 treatment increased the mRNA and protein expression of the SRGN gene by activating Smad3 to target the SRGN relative promoter domain in TNBC cells. Our findings demonstrate that SRGN interacts with TGFβ2 which regulates TNBC metastasis via the autocrine and paracrine routes. SRGN could serve as a potential target for development of agents or therapeutics for the TNBC.
Efficient protocol for qubit initialization with a tunable environment
Authors: Tuorila Jani , Partanen Matti , Ala-Nissila Tapio , Möttönen Mikko 
Published: July 2017

AbstractWe propose an efficient qubit initialization protocol based on a dissipative environment that can be dynamically adjusted. Here, the qubit is coupled to a thermal bath through a tunable harmonic oscillator. On-demand initialization is achieved by sweeping the oscillator rapidly into resonance with the qubit. This resonant coupling with the engineered environment induces fast relaxation to the ground state of the system, and a consecutive rapid sweep back to off resonance guarantees weak excess dissipation during quantum computations. We solve the corresponding quantum dynamics using a Markovian master equation for the reduced density operator of the qubit-bath system. This allows us to optimize the parameters and the initialization protocol for the qubit. Our analytical calculations show that the ground-state occupation of our system is well protected during the fast sweeps of the environmental coupling and, consequently, we obtain an estimate for the duration of our protocol by solving the transition rates between the low-energy eigenstates with the Jacobian diagonalization method. Our results suggest that the current experimental state of the art for the initialization speed of superconducting qubits at a given fidelity can be considerably improved.
Downregulation of blood serum microRNA 29 family in patients with Parkinson’s disease
Authors: Bai Xiaochen , Tang Yilin , Yu Mei , Wu Lei , Liu Fengtao , Ni Jianliang , Wang Zishan , Wang Jinghui , Fei Jian , Wang Wei , Huang Fang , Wang Jian 
Published: July 2017

AbstractThere is currently no reliable and easily applicable diagnostic marker for Parkinson’s disease (PD). The aims of the present study were to compare the expression profiles of the microRNA29 family (miR-29s) in blood serum from patients with PD with healthy controls and to clarify whether the expression of miR-29s is correlated with disease severity, duration or L-dopa therapy and whether expression depends on the gender and age of patients. The levels of blood serum miR-29s in 80 patients with PD and 80 unaffected controls were assessed by reverse transcription-quantitative real-time PCR. The PCR products were confirmed by cloning and sequencing. Additionally, the expression of miR-7 in the blood serum from PD patients and control subjects was assessed. Serum miR-29 levels were significantly downregulated in PD patients compared to healthy controls. The serum miR-29 levels in female PD patients were markedly higher than in male PD patients. The expression of serum miR-29a and miR-29c expression tended to decrease with disease severity. Moreover, we found that serum miR-7 levels did not differ between PD patients and control subjects. Therefore, the reduction of serum miR-29 levels, particularly miR-29a and miR-29c, warrants further investigation of its potential serving as biomarkers for PD.
Twins methods quantitatively explore the genetic impact on children and adolescents brain gray matter volume
Authors: Chen Xiao-Lu , Zhang Xiao-Wei , Hou Xiao , Li Xiao , Ma Xing-Shun , Hu Xiao-Mei , Meng Hua-Qing , He Qian , Zhao Lian-Sheng , Wang Ying-Cheng , Fu Yi-Xiao , Li Tao 
Published: July 2017

AbstractThe gray matter volumes of 58 pairs of twins ranging in age from 12 to 18 were measured by MRI to explore the genetic and environmental impacts on gray matter volume in twin children and adolescents. By means of A/C/E structural equation modeling, it was found that the gray matter volume in children and adolescents was jointly affected by genetic (A: 0.89) and environmental factors while genetic factors play a greater role. The gray matter volume in frontal lobe, parietal lobe, occipital lobe and lateral temporal lobe was mainly affected by genetics (A: 0.7–0.89), where as the gray matter volume in medial temporal lobe and cingulate cortex was affected by both genetics and environment.
Intrinsic dynamics study identifies two amino acids of TIMP-1 critical for its LRP-1-mediated endocytosis in neurons
Authors: Verzeaux Laurie , Belloy Nicolas , Thevenard-Devy Jessica , Devy Jérôme , Ferracci Géraldine , Martiny Laurent , Dedieu Stéphane , Dauchez Manuel , Emonard Hervé , Etique Nicolas , Devarenne-Charpentier Emmanuelle 
Published: July 2017

AbstractThe tissue inhibitor of metalloproteinases-1 (TIMP-1) exerts inhibitory activity against matrix metalloproteinases and cytokine-like effects. We previously showed that TIMP-1 reduces neurite outgrowth in mouse cortical neurons and that this cytokine-like effect depends on TIMP-1 endocytosis mediated by the low-density lipoprotein receptor-related protein-1 (LRP-1). To gain insight into the interaction between TIMP-1 and LRP-1, we considered conformational changes that occur when a ligand binds to its receptor. TIMP-1 conformational changes have been studied using biomolecular simulations, and our results provide evidence for a hinge region that is critical for the protein movement between the N- and C-terminal TIMP-1 domains.In silicomutants have been proposed on residues F12 and K47, which are located in the hinge region. Biological analyses of these mutants show that F12A or K47A mutation does not alter MMP inhibitory activity but impairs the effect of TIMP-1 on neurite outgrowth. Interestingly, these mutants bind to LRP-1 but are not endocytosed. We conclude that the intrinsic dynamics of TIMP-1 are not involved in its binding to LRP-1 but rather in the initiation of endocytosis and associated biological effects.
Children’s first handwriting productions show a rhythmic structure
Authors: Pagliarini Elena , Scocchia Lisa , Vernice Mirta , Zoppello Marina , Balottin Umberto , Bouamama Sana , Guasti Maria Teresa , Stucchi Natale 
Published: July 2017

AbstractAlthough much research has been concerned with the development of kinematic aspects of handwriting, little is known about the development along with age of two principles that govern its rhythmic organization: Homothety and Isochrony. Homothety states that the ratio between the durations of the single motor events composing a motor act remains invariant and independent from the total duration of the movement. Isochrony refers to the proportional relationship between the speed of movement execution and the length of its trajectory. The current study shows that children comply with both principles since their first grade of primary school. The precocious adherence to these principles suggests that an internal representation of the rhythm of handwriting is available before the age in which handwriting is performed automatically. Overall, these findings suggest that despite being a cultural acquisition, handwriting appears to be shaped by more general constraints on the timing planning of the movements.
Computationally Informed Design of a Multi-Axial Actuated Microfluidic Chip Device
Authors: Gizzi Alessio , Giannitelli Sara Maria , Trombetta Marcella , Cherubini Christian , Filippi Simonetta , De Ninno Adele , Businaro Luca , Gerardino Annamaria , Rainer Alberto 
Published: July 2017

AbstractThis paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading. Computational results were cross-validated by experimental testing of prototypal devices featuring the in silico optimized geometry. The proposed methodology represents a suite of computationally handy simulation tools that might find application in the design and in silico mechanical characterization of a wide range of stretchable microfluidic devices.
Genome-Wide Linkage Analysis of Large Multiple Multigenerational Families Identifies Novel Genetic Loci for Coronary Artery Disease
Authors: Guo Yang , Wang Fan , Li Lin , Gao Hanxiang , Arckacki Stephen , Wang Isabel Z. , Barnard John , Ellis Stephen , Hubbard Carlos , Topol Eric J. , Chen Qiuyun , Wang Qing K. 
Published: July 2017

AbstractCoronary artery disease (CAD) is the leading cause of death, and genetic factors contribute significantly to risk of CAD. This study aims to identify new CAD genetic loci through a large-scale linkage analysis of 24 large and multigenerational families with 433 family members (GeneQuest II). All family members were genotyped with markers spaced by every 10 cM and a model-free nonparametric linkage (NPL-all) analysis was carried out. Two highly significant CAD loci were identified on chromosome 17q21.2 (NPL score of 6.20) and 7p22.2 (NPL score of 5.19). We also identified four loci with significant NPL scores between 4.09 and 4.99 on 2q33.3, 3q29, 5q13.2 and 9q22.33. Similar analyses in individual families confirmed the six significant CAD loci and identified seven new highly significant linkages on 9p24.2, 9q34.2, 12q13.13, 15q26.1, 17q22, 20p12.3, and 22q12.1, and two significant loci on 2q11.2 and 11q14.1. Two loci on 3q29 and 9q22.33 were also successfully replicated in our previous linkage analysis of 428 nuclear families. Moreover, two published risk variants, SNP rs46522 in UBE2Z and SNP rs6725887 in WDR12 by GWAS, were found within the 17q21.2 and 2q33.3 loci. These studies lay a foundation for future identification of causative variants and genes for CAD.
Core-shell NaGdF4@CaCO3 nanoparticles for enhanced magnetic resonance/ultrasonic dual-modal imaging via tumor acidic micro-enviroment triggering
Authors: Wei Zuwu , Lin Xiao , Wu Ming , Zhao Bixing , Lin Ruhui , Zhang Da , Zhang Yun , Liu Gang , Liu Xiaolong , Liu Jingfeng 
Published: July 2017

AbstractFor cancer diagnosis, a paramount challenge still exists in the exploring of methods that can precisely discriminate tumor tissues from their surrounding healthy tissues with a high target-to-background signal ratio. Here, we report a NaGdF4@CaCO3-PEG core-shell nanoparticle which has the tumor acidic microenvironment enhanced imaging signals of ultrasound and magnetic resonance. Under the acidic conditions, the CaCO3 shell will gradually dissolve which then facilitate the interaction of NaGdF4 with the external aqueous environment to enhance water proton relaxation. Meanwhile, the CO2 bubbles generated by the CaCO3 dissolvement will generate strong elastic echo for US detection. The core-shell structure of NaGdF4@CaCO3-PEG can be observed by TEM, and its composition can be determined by STEM. The acid triggered generation of CO2 bubbles and the enhancement of MRI signal could be demonstrated in vitro, and the excellent dual-modal magnetic resonance/ultrasonic cancer imaging abilities of NaGdF4@CaCO3-PEG could be also proved at the tumor site in vivo. The here described proof-of-concept nanoparticles with pH triggered magnetic resonance/ultrasonic dual-modal imaging enhancement, may serve as a useful guide to develop various molecular imaging strategies for cancer diagnosis in the future.
Exosomes derived from pancreatic cancer cells induce insulin resistance in C2C12 myotube cells through the PI3K/Akt/FoxO1 pathway
Authors: Wang Lantian , Zhang Bo , Zheng Wen , Kang Muxing , Chen Qing , Qin Wenjie , Li Chao , Zhang Yuefeng , Shao Yingkuan , Wu Yulian 
Published: July 2017

AbstractProspective epidemiological studies have consistently suggested that pancreatic cancer-associated new-onset diabetes mellitus (PC-DM) represents a potential platform for early diagnose of pancreatic cancer (PC). Despite the studies performed, the mechanism behind this phenomenon remains ambiguous. In this study, we explored the effects of two types of exosomes released by murine pancreatic cancer and ductal epithelial cells on murine skeletal muscle cells. The results show that PC-derived exosomes can readily enter C2C12 myotubes, triggering lipidosis and glucose intake inhibition. We also demonstrate that PC-derived exosomes can inhibit insulin and PI3K/Akt signalling, in which insulin-induced FoxO1 nuclear exclusion is preserved and Glut4 trafficking is impaired. Microarray and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses show that exosomal microRNAs (miRNAs) probably play key roles in this process, an assumption that is corroborated by in vitro studies. These results confirm that the insulin resistance (IR) of skeletal muscle cells is governed by PC-derived exosomes through the insulin and PI3K/Akt/FoxO1 signalling pathways, where exosomal miRNAs potentially contribute to this phenomenon. These novel findings pave the way towards a comprehensive understanding of the cancer theories: “metabolic reprogramming” and “metabolic crosstalk”.
Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
Authors: Lemoine Marc D. , Mannhardt Ingra , Breckwoldt Kaja , Prondzynski Maksymilian , Flenner Frederik , Ulmer Bärbel , Hirt Marc N. , Neuber Christiane , Horváth András , Kloth Benjamin , Reichenspurner Hermann , Willems Stephan , Hansen Arne , Eschenhagen Thomas , Christ Torsten 
Published: July 2017

AbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with greater resemblance to human heart tissue in comparison to standard technique of 2D monolayer (ML) format. INa was measured in ML or EHT using the standard patch-clamp technique. INa density was ~1.8 fold larger in EHT (−18.5 ± 1.9 pA/pF; n = 17) than in ML (−10.3 ± 1.2 pA/pF; n = 23; p < 0.001), approaching densities reported for human CM. Inactivation kinetics, voltage dependency of steady-state inactivation and activation of INa did not differ between EHT and ML and were similar to previously reported values for human CM. Action potential recordings with sharp microelectrodes showed similar upstroke velocities in EHT (219 ± 15 V/s, n = 13) and human left ventricle tissue (LV, 253 ± 7 V/s, n = 25). EHT showed a greater resemblance to LV in CM morphology and subcellular NaV1.5 distribution. INa in hiPSC-CM showed similar biophysical properties as in human CM. The EHT format promotes INa density and action potential upstroke velocity of hiPSC-CM towards adult values, indicating its usefulness as a model for excitability of human cardiac tissue.
Pressure-Induced Crystallization and Phase Transformation of Para-xylene
Authors: Bai Yanzhi , Yu Zhenhai , Liu Ran , Li Nana , Yan Shuai , Yang Ke , Liu Bingbing , Wei Dongqing , Wang Lin 
Published: July 2017

AbstractStatic pressure is an alternative method to chemical pressure for tuning the crystal structure, bonds, and physical properties of materials, and is a significant technique for the synthesis of novel materials and fundamental research. In this letter, we report the crystallization and phase transformation of p-xylene under high pressure. Our optical micrographic observations and the appearance of lattice modes in the Raman and infrared (IR) spectra indicated that p-xylene crystallizes at ∼0.1 GPa. The X-ray diffraction (XRD) pattern at 0.84 GPa suggests that the crystallized p-xylene had a monoclinic phase with the Cc(9) space group. The sharp shrinkage of the lattice at ~13 GPa and the solid state of the decompressed sample we observed suggests a new crystalline phase of p-xylene. The in situ XRD showed that the new crystalline phase was still a monoclinic structure but with a different space group of C2(5), indicating that a phase transition occurred during further compression. The mass spectrometry experiment confirmed phase transition polymerization, with mainly trimer and tetramer polymers. Our findings suggest an easy and efficient method for crystallizing and polymerizing p-xylene under high pressure.
Genome-wide survey indicates diverse physiological roles of the barley (Hordeum vulgare L.) calcium-dependent protein kinase genes
Authors: Yang Yunqiang , Wang Qiuli , Chen Qian , Yin Xin , Qian Min , Sun Xudong , Yang Yongping 
Published: July 2017

AbstractCalcium-dependent protein kinases (CDPKs) are crucial calcium sensors that play important roles in the regulation of plant growth and developmental processes, as well as protective responses to environmental stress. Here, we identified 28 CDPK genes from barley and cloned 5 new, full-length CDPK genes, MLOC_58648a, MLOC_19618a, MLOC_71733a, AK249361a and MLOC_4965a, using their expressed sequence tags. Phylogenetic and gene structural analyses revealed that the CDPK could be divided into four subgroups. Significant site-specific altered constraints and a high evolutionary rate may have contributed to the functional divergences among CDPK gene subfamilies. Expression profiles of different tissues and developmental stages suggested that several CDPK genes are involved in the functional development of plants. Different expression levels under a variety of abiotic stresses also indicated that the CDPK family underwent functional divergence during long-term evolution. Furthermore, several CDPK genes responded to single treatments and individual CDPK genes responded to multiple treatments, suggesting that barley CDPKs may be involved in mediating cross-talk among different signalling pathways. Our data provide an important foundation for the functional and evolutionary analyses of this important gene family in barley.
High Resolution Imaging of DNA Methylation Dynamics using a Zebrafish Reporter
Authors: Zhang Ranran , Liu Lian , Yao Yuxiao , Fei Fei , Wang Feng , Yang Qian , Gui Yonghao , Wang Xu 
Published: July 2017

AbstractAs one of the major epigenetic modifications, DNA methylation is constantly regulated during embryonic development, cell lineage commitment, and pathological processes. To facilitate real-time observation of DNA methylation, we generated a transgenic zebrafish reporter of DNA methylation (zebraRDM) via knockin of an mCherry-fused methyl-CpG binding domain (MBD) probe driven by the bactin2 promoter. The probe colocalized with heterochromatin, and its intensity was positively correlated with 5 mC immunostaining at a subcellular resolution in early embryos. Biochemical assays indicated that cells with stronger fluorescence maintained a higher level of DNA methylation, and time-lapse imaging at the blastula stage showed that the level of DNA methylation was transiently strengthened during mitosis. By crossing zebraRDM with other fluorescent transgenic lines, we demonstrate that the reporter can visually distinguish different cell lineages in organs like the heart. Our zebraRDM reporter therefore serves as a convenient and powerful tool for high-resolution investigation of methylation dynamics in live animals.