bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification
Authors: Xu Xiaoliang , Yin Yin , Tang Junwei , Xie Yu , Han Zhuo , Zhang Xudong , Liu Qiaoyu , Qin Xihu , Huang Xinli , Sun Beicheng 
Published: October 2017

AbstractEnhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located upstream of Myd88 and verified a positive regulation relationship between them indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88 in HCC. The gain- and loss-of-function analysis revealed that Lnc-Myd88 could promote the proliferation and metastasis of HCC both in vitro and in vivo. In addition, ChIP assays demonstrated that Lnc-Myd88 might increase Myd88 expression through enhancing H3K27Ac in the promoter of Myd88 gene, thus resulting in the activation of both NF-κB and PI3K/AKT signal pathways. In conclusion, we proposed that Lnc-Myd88 might serve as a novel diagnosis and therapeutic target for HCC.
c-Abl-mediated Drp1 phosphorylation promotes oxidative stress-induced mitochondrial fragmentation and neuronal cell death
Authors: Zhou Lujun , Zhang Qiang , Zhang Peng , Sun Lei , Peng Can , Yuan Zengqiang , Cheng Jinbo 
Published: October 2017

AbstractOxidative stress-induced mitochondrial dysfunction and neuronal cell death have important roles in the development of neurodegenerative diseases. Dynamin related protein 1 (Drp1) is a critical factor in regulating mitochondrial dynamics. A variety of posttranslational modifications of Drp1 have been reported, including phosphorylation, ubiquitination, sumoylation and S-nitrosylation. In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation. Consistently, c-Abl-mediated phosphorylation is important for GTPase activity of Drp1 and mitochondrial fragmentation. Furthermore, we found that Drp1 phosphorylation mediated by c-Abl is required for oxidative stress-induced cell death in primary cortical neurons. Taken together, our findings reveal that c-Abl-Drp1 signaling pathway regulates oxidative stress-induced mitochondrial fragmentation and cell death, which might be a potential target for the treatment of neurodegenerative diseases.
Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells for testosterone production
Authors: Zhang Min , Wang Jiancheng , Deng Chunhua , Jiang Mei Hua , Feng Xin , Xia Kai , Li Weiqiang , Lai Xingqiang , Xiao Haipeng , Ge Ren-shan , Gao Yong , Xiang Andy Peng 
Published: October 2017

AbstractPrevious studies have demonstrated that rodent stem Leydig cell (SLC) transplantation can partially restore testosterone production in Leydig cell (LC)-disrupted or senescent animal models, which provides a promising approach for the treatment of hypogonadism. Here, we isolated human SLCs prospectively and explored the potential therapeutic benefits of human SLC transplantation for hypogonadism treatment. In adult human testes, p75 neurotrophin receptor positive (p75+) cells expressed the known SLC marker nestin, but not the LC lineage marker hydroxysteroid dehydrogenase-3β (HSD3β). The p75+ cells which were sorted by flow cytometry from human adult testes could expand in vitro and exhibited clonogenic self-renewal capacity. The p75+ cells had multi-lineage differentiation potential into multiple mesodermal cell lineages and testosterone-producing LCs in vitro. After transplantation into the testes of ethane dimethane sulfonate (EDS)-treated LC-disrupted rat models, the p75+ cells differentiated into LCs in vivo and secreted testosterone in a physiological pattern. Moreover, p75+ cell transplantation accelerated the recovery of serum testosterone levels, spermatogenesis and reproductive organ weights. Taken together, we reported a method for the identification and isolation of human SLCs on the basis of p75 expression, and demonstrated that transplanted human p75+ SLCs could replace disrupted LCs for testosterone production. These findings provide the groundwork for further clinical application of human SLCs for hypogonadism.
A mechanosensitive Ca2+ channel activity is dependent on the developmental regulator DEK1
Authors: Tran Daniel , Galletti Roberta , Neumann Enrique D. , Dubois Annick , Sharif-Naeini Reza , Geitmann Anja , Frachisse Jean-Marie , Hamant Olivier , Ingram Gwyneth C. 
Published: October 2017

AbstractResponses of cells to mechanical stress are thought to be critical in coordinating growth and development. Consistent with this idea, mechanically activated channels play important roles in animal development. For example, the PIEZO1 channel controls cell division and epithelial-layer integrity and is necessary for vascular development in mammals. In plants, the actual contribution of mechanoperception to development remains questionable because very few putative mechanosensors have been identified and the phenotypes of the corresponding mutants are rather mild. Here, we show that the Arabidopsis Defective Kernel 1 (DEK1) protein, which is essential for development beyond early embryogenesis, is associated with a mechanically activated Ca2+ current in planta, suggesting that perception of mechanical stress plays a critical role in plant development.
ROCK regulates the intermittent mode of interstitial T cell migration in inflamed lungs
Authors: Mrass Paulus , Oruganti Sreenivasa Rao , Fricke G. Matthew , Tafoya Justyna , Byrum Janie R. , Yang Lihua , Hamilton Samantha L. , Miller Mark J. , Moses Melanie E. , Cannon Judy L. 
Published: October 2017

AbstractEffector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood. Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue. Computational analysis indicates that T cells migrate with an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature. Rho-associated protein kinase (ROCK) is required for both high-speed migration and straight motion. By contrast, inhibition of Gαisignaling with pertussis toxin affects speed but not the intermittent migration of lung-infiltrating T cells. Computational modeling shows that an intermittent migration pattern balances both search area and the duration of contacts between T cells and target cells. These data identify that ROCK-dependent intermittent T cell migration regulates tissue-sampling during acute lung injury.
Few-femtosecond passage of conical intersections in the benzene cation
Authors: Galbraith M. C. E. , Scheit S. , Golubev N. V. , Reitsma G. , Zhavoronkov N. , Despré V. , Lépine F. , Kuleff A. I. , Vrakking M. J. J. , Kornilov O. , Köppel H. , Mikosch J. 
Published: October 2017

AbstractObserving the crucial first few femtoseconds of photochemical reactions requires tools typically not available in the femtochemistry toolkit. Such dynamics are now within reach with the instruments provided by attosecond science. Here, we apply experimental and theoretical methods to assess the ultrafast nonadiabatic vibronic processes in a prototypical complex system—the excited benzene cation. We use few-femtosecond duration extreme ultraviolet and visible/near-infrared laser pulses to prepare and probe excited cationic states and observe two relaxation timescales of 11 ± 3 fs and 110 ± 20 fs. These are interpreted in terms of population transfer via two sequential conical intersections. The experimental results are quantitatively compared with state-of-the-art multi-configuration time-dependent Hartree calculations showing convincing agreement in the timescales. By characterising one of the fastest internal conversion processes studied to date, we enter an extreme regime of ultrafast molecular dynamics, paving the way to tracking and controlling purely electronic dynamics in complex molecules.
The WNT target SP5 negatively regulates WNT transcriptional programs in human pluripotent stem cells
Authors: Huggins Ian J. , Bos Tomas , Gaylord Olivia , Jessen Christina , Lonquich Brianna , Puranen Angeline , Richter Jenna , Rossdam Charlotte , Brafman David , Gaasterland Terry , Willert Karl 
Published: October 2017

AbstractThe WNT/β-catenin signaling pathway is a prominent player in many developmental processes, including gastrulation, anterior–posterior axis specification, organ and tissue development, and homeostasis. Here, we use human pluripotent stem cells (hPSCs) to study the dynamics of the transcriptional response to exogenous activation of the WNT pathway. We describe a mechanism involving the WNT target gene SP5 that leads to termination of the transcriptional program initiated by WNT signaling. Integration of gene expression profiles of wild-type and SP5 mutant cells with genome-wide SP5 binding events reveals that SP5 acts to diminish expression of genes previously activated by the WNT pathway. Furthermore, we show that activation of SP5 by WNT signaling is most robust in cells with developmental potential, such as stem cells. These findings indicate a mechanism by which the developmental WNT signaling pathway reins in expression of transcriptional programs.
Engineered in-vitro cell line mixtures and robust evaluation of computational methods for clonal decomposition and longitudinal dynamics in cancer
Authors: Farahani Hossein , de Souza Camila P. E. , Billings Raewyn , Yap Damian , Shumansky Karey , Wan Adrian , Lai Daniel , Mes-Masson Anne-Marie , Aparicio Samuel , P. Shah Sohrab 
Published: October 2017

AbstractCharacterization and quantification of tumour clonal populations over time via longitudinal sampling are essential components in understanding and predicting the response to therapeutic interventions. Computational methods for inferring tumour clonal composition from deep-targeted sequencing data are ubiquitous, however due to the lack of a ground truth biological data, evaluating their performance is difficult. In this work, we generate a benchmark data set that simulates tumour longitudinal growth and heterogeneity by in vitro mixing of cancer cell lines with known proportions. We apply four different algorithms to our ground truth data set and assess their performance in inferring clonal composition using different metrics. We also analyse the performance of these algorithms on breast tumour xenograft samples. We conclude that methods that can simultaneously analyse multiple samples while accounting for copy number alterations as a factor in allelic measurements exhibit the most accurate predictions. These results will inform future functional genomics oriented studies of model systems where time series measurements in the context of therapeutic interventions are becoming increasingly common. These studies will need computational models which accurately reflect the multi-factorial nature of allele measurement in cancer including, as we show here, segmental aneuploidies.
Molecular structure of starch isolated from jackfruit and its relationship with physicochemical properties
Authors: Zhang Yanjun , Zhang Yutong , Xu Fei , Wu Gang , Tan Lehe 
Published: October 2017

AbstractThe molecular structure of starches isolated from five jackfruits (M2, M3, M4, M8 and X1) and its relationship with physicochemical properties were investigated. Although they had uniform amylose (AM) content, the five jackfruit starches displayed different physicochemical properties, including their pasting, thermal, crystal and texture properties. Furthermore, differences in the molecular structure (i.e., average weight-average molar mass (Mw) of amylose and amylopectin (AP) as well as the same AP fine structure) were also found in the five jackfruit starches. The results indicated that jackfruit starch with a larger Mw of amylose and proportions of DP 25–36, DP ≥ 37 and chain length had a lower peak viscosity, breakdown, final viscosity, setback and adhesiveness, but a higher pasting and gelatinization temperature, gelatinization temperature range, gelatinization enthalpy and relative crystallinity. Xiangyinsuo 1 hao (X1) starch, which originated from Xinglong in Hainan province, China, had special physicochemical properties, which were ascribed to its lower amylopectin Mw, smaller particle size, and perfect amylopectin structure. The results showed that the most important intrinsic factors that could determine the physicochemical properties of starch were its molecular structure, including the Mw of amylose and AP as well as a fine AP structure.
The piecewise parabolic method for Riemann problems in nonlinear elasticity
Authors: Zhang Wei , Wang Tao , Bai Jing-Song , Li Ping , Wan Zhen-Hua , Sun De-Jun 
Published: October 2017

AbstractWe present the application of Harten-Lax-van Leer (HLL)-type solvers on Riemann problems in nonlinear elasticity which undergoes high-load conditions. In particular, the HLLD (“D” denotes Discontinuities) Riemann solver is proved to have better robustness and efficiency for resolving complex nonlinear wave structures compared with the HLL and HLLC (“C” denotes Contact) solvers, especially in the shock-tube problem including more than five waves. Also, Godunov finite volume scheme is extended to higher order of accuracy by means of piecewise parabolic method (PPM), which could be used with HLL-type solvers and employed to construct the fluxes. Moreover, in the case of multi material components, level set algorithm is applied to track the interface between different materials, while the interaction of interfaces is realized through HLLD Riemann solver combined with modified ghost method. As seen from the results of both the solid/solid “stick” problem with the same material at the two sides of contact interface and the solid/solid “slip” problem with different materials at the two sides, this scheme composed of HLLD solver, PPM and level set algorithm can capture the material interface effectively and suppress spurious oscillations therein significantly.
Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures
Authors: Schwalbe E. C. , Hicks D. , Rafiee G. , Bashton M. , Gohlke H. , Enshaei A. , Potluri S. , Matthiesen J. , Mather M. , Taleongpong P. , Chaston R. , Silmon A. , Curtis A. , Lindsey J. C. , Crosier S. , Smith A. J. , Goschzik T. , Doz F. , Rutkowski S. , Lannering B. , Pietsch T. , Bailey S. , Williamson D. , Clifford S. C. 
Published: October 2017

AbstractRapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.
Facilitating identification of minimal protein binding domains by cross-linking mass spectrometry
Authors: Liu Qingyang , Remmelzwaal Sanne , Heck Albert J. R. , Akhmanova Anna , Liu Fan 
Published: October 2017

AbstractCharacterization of protein interaction domains is crucial for understanding protein functions. Here we combine cross-linking mass spectrometry (XL-MS) with deletion analysis to accurately locate minimal protein interaction domains. As a proof of concept, we investigated in detail the binding interfaces of two protein assemblies: the complex formed by MICAL3, ELKS and Rab8A, which is involved in exocytosis, and the complex of SLAIN2, CLASP2 and ch-TOG, which controls microtubule dynamics. We found that XL-MS provides valuable information to efficiently guide the design of protein fragments that are essential for protein interaction. However, we also observed a number of cross-links between polypeptide regions that were dispensable for complex formation, especially among intrinsically disordered sequences. Collectively, our results indicate that XL-MS, which renders distance restrains of linked residue pairs, accelerates the characterization of protein binding regions in combination with other biochemical approaches.
Association between Parkinson’s disease and risk of prostate cancer in different populations: An updated meta-analysis
Authors: Chen Chunli , Zheng Haiping , Hu Zhiping 
Published: October 2017

AbstractRecently, growing evidence has revealed a significant association between Parkinson’s disease (PD) and cancer. However, controversy still exists concerning the association between PD and prostate cancer. A comprehensive article search for relevant published studies was performed using the online databases PubMed, Web of Science and Embase up to January 1, 2017. The pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using the method of inverse variance with a random-effects model. Fifteen studies comprising 346,153 PD patients were included in this study. The results of the present study showed that PD was significantly associated with a decreased risk of prostate cancer in the Western population (RR: 0.83, 95% CI: 0.72–0.95, P < 0.01), while an increased risk of prostate cancer was shown in the Asian population (RR: 1.80, 95% CI: 1.52–2.13, P < 0.001). In the subgroup analysis, the reduced risk of prostate cancer in PD patients from Western populations was consistent regardless of study design or study quality. In conclusion, PD was significantly associated with a reduced risk of prostate cancer in the Western population. The relationship between those conditions in the Asian population needs to be confirmed by future studies.
Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification
Authors: Kurosaki Yohei , Martins Danyelly Bruneska Gondim , Kimura Mayuko , Catena Andriu dos Santos , Borba Maria Amélia Carlos Souto Maior , Mattos Sandra da Silva , Abe Haruka , Yoshikawa Rokusuke , de Lima Filho José Luiz , Yasuda Jiro 
Published: October 2017

AbstractThe recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID50/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks.
Circulating miR-19b and miR-181b are potential biomarkers for diabetic cardiomyopathy
Authors: Copier Camila Uribe , León Luis , Fernández Mauricio , Contador David , Calligaris Sebastián D. 
Published: October 2017

AbstractDiabetic cardiomyopathy is characterized by metabolic changes in the myocardium that promote a slow and silent dysfunction of muscle fibers, leading to myocardium remodelling and heart failure, independently of the presence of coronary artery diseases or hypertension. At present, no imaging methods allow an early diagnosis of this disease. Circulating miRNAs in plasma have been proposed as biomarkers in the prognosis of several cardiac diseases. This study aimed to determine whether circulating miRNAs could be potential biomarkers of diabetic cardiomyopathy. Mice that were fed with a high fat diet for 16 months, showed metabolic syndrome manifestations, cardiac hypertrophy (without hypertension) and a progressive cardiac function decline. At 16 months, when maximal degree of cardiac dysfunction was observed, 15 miRNAs from a miRNA microarray screening in myocardium were selected. Then, selected miRNAs expression in myocardium (at 4 and 16 months) and plasma (at 4, 12 and 16 months) were measured by RT-qPCR. Circulating miR-19b-3p and miR-181b-5p levels were associated with myocardium levels during the development of diabetic cardiomyopathy (in terms of cardiac dysfunction), suggesting that these miRNAs could be suitable biomarkers of this disease in asymptomatic diabetic patients.
Rapid Generation and Detection of Biomimetic Oxygen Concentration Gradients In Vitro
Authors: Khan Daud H. , Roberts Steven A. , Cressman John Robert , Agrawal Nitin 
Published: October 2017

AbstractHypoxic regions exist within most solid tumors and often lead to altered cellular metabolism, metastasis, and drug resistance. Reliable generation and detection of biomimetic gaseous gradientsin vitrois challenging due to low spatiotemporal resolution and poor longevity of gradients utilizing microfluidic techniques. Here, we present a novel and simplistic approach for producing gradients of dissolved oxygen (DO) within a lab-on-a-chip platform. Linear and stable DO gradients with high spatial resolution are established by introducing pre-gassed media into the gradient generating network. An underlying platinum(ii) octaethlporphyrin ketone (PtOEPK) based sensor layer allows parallel detection of oxygen. A thin 3-sided glass coating on the inner channel walls prevents multi-directional diffusion of ambient oxygen across PDMS preserving the gradient resolution and stability. Viability analysis of normal mammary epithelial cells (MCF-12A) under oxygen gradients revealed 70% mortality after 6 hours of hypoxic exposure. Biological applicability of the platform was further validated by demonstrating increase in endoplasmic reticulum stress of MDA-MB-468 cells with time and with increasing oxygen tension. The unique ability to establish parallel or opposing gradients of gases and chemicals offers the potential for a wide range of applications in therapeutic development, and fundamental understanding of cellular behavior during hypoxia.