bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades
Authors: Liu Zhichao , Wang Yuping , Borlak Jürgen , Tong Weida 
Published: April 2016

AbstractHepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct molecular circuits of microRNA/LD-associated target genes and searched for mechanistically linked serum and tissue biomarkers that would distinguish between DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting 77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N = 167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH serum regulated miRNAs informed on hepatic inflammation, adipocytokine and insulin signalling, ER-and caveolae associated activities and altered glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis specifically highlighted activity of FOXO1&HNF4α on CPT2, the lipid droplet and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed on the molecular pathophysiology of NAFLD and permitted differentiation between DIS and NAFLD of different grades.
BET Bromodomain Suppression Inhibits VEGF-induced Angiogenesis and Vascular Permeability by Blocking VEGFR2-mediated Activation of PAK1 and eNOS
Authors: Huang Mingcheng , Qiu Qian , Xiao Youjun , Zeng Shan , Zhan Mingying , Shi Maohua , Zou Yaoyao , Ye Yujin , Liang Liuqin , Yang Xiuyan , Xu Hanshi 
Published: April 2016

AbstractThe tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) is a critical modulator of angiogenesis. Increasing evidence indicate the important role of bromodomain and extra-terminal domain (BET) of chromatin adaptors in regulating tumor growth and inflammatory response. However, whether BET proteins have a role in angiogenesis and endothelial permeability is unclear. In this study, we observed that treatment with JQ1, a specific BET inhibitor, suppressed in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis in a Matrigel plug and oxygen-induced retinopathy neovascularization. JQ1 attenuated the VEGF-induced decrease in TEER in HUVECs and prevented Evans blue dye leakage in the VEGF-induced Miles assay in athymic Balb/c nude mice. BET inhibition with JQ1 or shRNA for Brd2 or Brd4 suppressed VEGF-induced migration, proliferation and stress fiber formation of HUVECs. Furthermore, BET inhibition suppressed phosphorylation of VEGFR2 and PAK1, as well as eNOS activation in VEGF-stimulated HUVECs. Inhibition with VEGFR2 and PAK1 also reduced migration and proliferation and attenuated the VEGF-induced decrease in TEER. Thus, our observations suggest the important role of BET bromodomain in regulating VEGF-induced angiogenesis. Strategies that target the BET bromodomain may provide a new therapeutic approach for angiogenesis-related diseases.
LncRNA—UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p
Authors: Bian Zehua , Jin Liugen , Zhang Jiwei , Yin Yuan , Quan Chao , Hu Yaling , Feng Yuyang , Liu Heyong , Fei Bojian , Mao Yong , Zhou Leyuan , Qi Xiaowei , Huang Shenlin , Hua Dong , Xing Chungen , Huang Zhaohui 
Published: April 2016

AbstractRecent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.
Resilient help to switch and overlap hierarchical subsystems in a small human group
Authors: Fujii K. , Yokoyama K. , Koyama T. , Rikukawa A. , Yamada H. , Yamamoto Y. 
Published: April 2016

AbstractGroups of social organisms in nature are resilient systems that can overcome unpredicted threats by helping its members. These social organisms are assumed to behave both autonomously and cooperatively as individuals, the helper, the helped and other part of a group depending on the context such as emergencies. However, the structure and function of these resilient actions, such as how helpers help colleagues and how the helper’s action is effective at multiple subsystem scales remain unclear. Here we investigated the behaviour of organised and efficient small human groups in a ballgame defence and identified three principles of hierarchical resilient help when under attack. First, at a present high emergency level, the helper simply switched the local roles in the attacked subsystem with the helped. Second, at an intermediate emergency level, the helpers effectively acted in overlapping subsystems. Third, for the most critical emergency, the helpers globally switched the action on the overall system. These resilient actions to the benefit of the system were assumed to be observed in only humans, which help colleagues at flexibly switched and overlapped hierarchical subsystem. We suggest that these multi-layered helping behaviours can help to understand resilient cooperation in social organisms and human groups.
Controlling superconducting spin flow with spin-flip immunity using a single homogeneous ferromagnet
Authors: Jacobsen Sol H. , Kulagina Iryna , Linder Jacob 
Published: April 2016

AbstractSpin transport via electrons is typically plagued by Joule heating and short decay lengths due to spin-flip scattering. It is known that dissipationless spin currents can arise when using conventional superconducting contacts, yet this has only been experimentally demonstrated when using intricate magnetically inhomogeneous multilayers, or in extreme cases such as half-metals with interfacial magnetic disorder. Moreover, it is unknown how such spin supercurrents decay in the presence of spin-flip scattering. Here, we present a method for generating a spin supercurrent by using only a single homogeneous magnetic element. Remarkably, the spin supercurrent generated in this way does not decay spatially, in stark contrast to normal spin currents that remain polarized only up to the spin relaxation length. We also expose the existence of a superconductivity-mediated torque even without magnetic inhomogeneities, showing that the different components of the spin supercurrent polarization respond fundamentally differently to a change in the superconducting phase difference. This establishes a mechanism for tuning dissipationless spin and charge flow separately and confirms the advantage that superconductors can offer in spintronics.
MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type features
Authors: Ghosh Ruma Dey , Ghuwalewala Sangeeta , Das Pijush , Mandloi Sapan , Alam Sk Kayum , Chakraborty Jayanta , Sarkar Sajal , Chakrabarti Saikat , Panda Chinmoy Kumar , Roychoudhury Susanta 
Published: April 2016

AbstractOral cancer is of major public health problem in India. Current investigation was aimed to identify the specific deregulated miRNAs which are responsible for development of resistance phenotype through regulating their resistance related target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin-resistant OSCC cell lines were developed from their parental human OSCC cell lines and subsequently characterised. The resistant cells exhibited enhanced proliferative, clonogenic capacity with significant up-regulation of P-glycoprotein (ABCB1), c-Myc, survivin, β-catenin and a putative cancer-stem-like signature with increased expression of CD44, whereas the loss of E-cadherin signifies induced EMT phenotype. A comparative analysis of miRNA expression profiling in parental and cisplatin-resistant OSCC cell lines for a selected sets (deregulated miRNAs in head and neck cancer) revealed resistance specific signature. Moreover, we observed similar expression pattern for these resistance specific signature miRNAs in neoadjuvant chemotherapy treated and recurrent tumours compared to those with newly diagnosed primary tumours in patients with OSCC. All these results revealed that these miRNAs play an important role in the development of cisplatin-resistance mainly through modulating cancer stem-cell-like and EMT-type properties in OSCC.
Preadipocyte factor 1 induces pancreatic ductal cell differentiation into insulin-producing cells
Authors: Rhee Marie , Lee Seung-Hwan , Kim Ji-Won , Ham Dong-Sik , Park Heon-Seok , Yang Hae Kyung , Shin Ju-Young , Cho Jae-Hyoung , Kim Young-Bum , Youn Byung-Soo , Sul Hei Sook , Yoon Kun-Ho 
Published: April 2016

AbstractThe preadipocyte factor 1 (Pref-1) is involved in the proliferation and differentiation of various precursor cells. However, the intracellular signaling pathways that control these processes and the role of Pref-1 in the pancreas remain poorly understood. Here, we showed that Pref-1 induces insulin synthesis and secretion via two independent pathways. The overexpression of Pref-1 activated MAPK signaling, which induced nucleocytoplasmic translocation of FOXO1 and PDX1 and led to the differentiation of human pancreatic ductal cells into β-like cells and an increase in insulin synthesis. Concurrently, Pref-1 activated Akt signaling and facilitated insulin secretion. A proteomics analysis identified the Rab43 GTPase-activating protein as a downstream target of Akt. A serial activation of both proteins induced various granular protein syntheses which led to enhanced glucose-stimulated insulin secretion. In a pancreatectomised diabetic animal model, exogenous Pref-1 improved glucose homeostasis by accelerating pancreatic ductal and β-cell regeneration after injury. These data establish a novel role for Pref-1, opening the possibility of applying this molecule to the treatment of diabetes.
Solar cycles or random processes? Evaluating solar variability in Holocene climate records
Authors: Turner T. Edward , Swindles Graeme T. , Charman Dan J. , Langdon Peter G. , Morris Paul J. , Booth Robert K. , Parry Lauren E. , Nichols Jonathan E. 
Published: April 2016

AbstractMany studies have reported evidence for solar-forcing of Holocene climate change across a range of archives. These studies have compared proxy-climate data with records of solar variability (e.g. 14C or 10Be), or have used time series analysis to test for the presence of solar-type cycles. This has led to some climate sceptics misrepresenting this literature to argue strongly that solar variability drove the rapid global temperature increase of the twentieth century. As proxy records underpin our understanding of the long-term processes governing climate, they need to be evaluated thoroughly. The peatland archive has become a prominent line of evidence for solar forcing of climate. Here we examine high-resolution peatland proxy climate data to determine whether solar signals are present. We find a wide range of significant periodicities similar to those in records of solar variability: periods between 40–100 years, and 120–140 years are particularly common. However, periodicities similar to those in the data are commonly found in random-walk simulations. Our results demonstrate that solar-type signals can be the product of random variations alone, and that a more critical approach is required for their robust interpretation.
Clustering mechanism of ethanol-water mixtures investigated with photothermal microfluidic cantilever deflection spectroscopy
Authors: Ghoraishi M. S. , Hawk J. E. , Phani Arindam , Khan M. F. , Thundat T. 
Published: April 2016

AbstractThe infrared-active (IR) vibrational mode of ethanol (EtOH) associated with the asymmetrical stretching of the C-C-O bond in pico-liter volumes of EtOH-water binary mixtures is calorimetrically measured using photothermal microfluidic cantilever deflection spectroscopy (PMCDS). IR absorption by the confined liquid results in wavelength dependent cantilever deflections, thus providing a complementary response to IR absorption revealing a complex dipole moment dependence on mixture concentration. Solvent-induced blue shifts of the C-C-O asymmetric vibrational stretch for both anti and gauche conformers of EtOH were precisely monitored for EtOH concentrations ranging from 20–100% w/w. Variations in IR absorption peak maxima show an inverse dependence on induced EtOH dipole moment (μ) and is attributed to the complex clustering mechanism of EtOH-water mixtures.
Revealing a new activity of the human Dicer DUF283 domain in vitro
Authors: Kurzynska-Kokorniak Anna , Pokornowska Maria , Koralewska Natalia , Hoffmann Weronika , Bienkowska-Szewczyk Krystyna , Figlerowicz Marek 
Published: April 2016

AbstractThe ribonuclease Dicer is a multidomain enzyme that plays a fundamental role in the biogenesis of small regulatory RNAs (srRNAs), which control gene expression by targeting complementary transcripts and inducing their cleavage or repressing their translation. Recent studies of Dicer’s domains have permitted to propose their roles in srRNA biogenesis. For all of Dicer’s domains except one, called DUF283 (domain of unknown function), their involvement in RNA substrate recognition, binding or cleavage has been postulated. For DUF283, the interaction with Dicer’s protein partners has been the only function suggested thus far. In this report, we demonstrate that the isolated DUF283 domain from human Dicer is capable of binding single-stranded nucleic acids in vitro. We also show that DUF283 can act as a nucleic acid annealer that accelerates base-pairing between complementary RNA/DNA molecules in vitro. We further demonstrate an annealing activity of full length human Dicer. The overall results suggest that Dicer, presumably through its DUF283 domain, might facilitate hybridization between short RNAs and their targets. The presented findings reveal the complex nature of Dicer, whose functions may extend beyond the biogenesis of srRNAs.
Sub-micron scale patterning of fluorescent silver nanoclusters using low-power laser
Authors: Kunwar Puskal , Hassinen Jukka , Bautista Godofredo , Ras Robin H. A. , Toivonen Juha 
Published: April 2016

AbstractNoble metal nanoclusters are ultrasmall nanomaterials with tunable properties and huge application potential; however, retaining their enhanced functionality is difficult as they readily lose their properties without stabilization. Here, we demonstrate a facile synthesis of highly photostable silver nanoclusters in a polymer thin film using visible light photoreduction. Furthermore, the different stages of the nanocluster formation are investigated in detail using absorption and fluorescence spectroscopy, fluorescence microscopy, and atomic force microscopy. A cost-effective fabrication of photostable micron-sized fluorescent silver nanocluster barcode is demonstrated in silver-impregnated polymer films using a low-power continuous-wave laser diode. It is shown that a laser power of as low as 0.75 mW is enough to write fluorescent structures, corresponding to the specifications of a commercially available laser pointer. The as-formed nanocluster-containing microstructures can be useful in direct labeling applications such as authenticity marking and fluorescent labeling.
Association between betatrophin/ANGPTL8 and non-alcoholic fatty liver disease: animal and human studies
Authors: Lee Yong-ho , Lee Sang-Guk , Lee Chan Joo , Kim Soo Hyun , Song Young-Mi , Yoon Mi Ra , Jeon Byung Hun , Lee Jae Hyuk , Lee Byung-Wan , Kang Eun Seok , Lee Hyun Chul , Cha Bong-Soo 
Published: April 2016

AbstractBetatrophin/angiopoietin-like protein 8 (ANGPTL8) is a liver-secreted protein recently identified as a potent stimulator of beta cell proliferation in mice. However, it is unclear how betatrophin is regulated in humans with non-alcoholic fatty liver disease (NAFLD). We investigated the role of betatrophin in mice and in humans with and without NAFLD. Serum betatrophin levels were examined by ELISA in 164 subjects, including 96 patients with NAFLD. Levels were significantly elevated in subjects with NAFLD compared with controls (1.301 ± 0.617 vs. 0.900 ± 0.574 μg/L, P < 0.001), even after stratification by diabetic or obesity status. Circulating betatrophin positively correlated with obesity or glycemic indices, liver enzyme profiles, and NAFLD status, and was confirmed by multivariate regression analyses (β = 0.195, P = 0.040). However, when including insulin resistance index in the model, the significant association between betatrophin level and NAFLD was diminished due to a mediation effect of insulin resistance on this relationship. Palmitate or tunicamycin increased betatrophin expression in HepG2 cells, while a chemical chaperone blocked its induction. Hepatic expression of betatrophin was elevated in mice with NAFLD including db/db or ob/ob mice and mice with a high-fat or methionine-choline deficient diet. In conclusion, circulating betatrophin was increased in mice and humans with NAFLD and its expression was induced by endoplasmic reticulum stress in hepatocytes (Clinical trial no. NCT02285218).
Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3
Authors: Ling Shenglong , Zhang Chengwei , Wang Wei , Cai Xiaoying , Yu Lu , Wu Fangming , Zhang Longhua , Tian Changlin 
Published: April 2016

AbstractInterferon-inducible transmembrane protein IFITM3 was known to restrict the entry of a wide spectrum of viruses to the cytosol of the host. The mechanism used by the protein to restrict viral entry is unclear given the unavailability of the membrane topology and structures of the IFITM family proteins. Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Solution NMR studies of the same sample verified the secondary structure distribution and demonstrated two rigid regions interacting with the micellar surface. The resulting membrane topology of IFITM3 supports the mechanism of an enhanced restricted membrane hemi-fusion.
Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children
Authors: Wu Guojun , Zhang Chenhong , Wang Jing , Zhang Feng , Wang Ruirui , Shen Jian , Wang Linghua , Pang Xiaoyan , Zhang Xiaojun , Zhao Liping , Zhang Menghui 
Published: April 2016

AbstractThe gut microbiome represents an important reservoir of antibiotic resistance genes (ARGs). Effective methods are urgently needed for managing the gut resistome to fight against the antibiotic resistance threat. In this study, we show that a gut microbiota-targeted dietary intervention, which shifts the dominant fermentation of gut bacteria from protein to carbohydrate, significantly diminished the gut resistome and alleviated metabolic syndrome in obese children. Of the non-redundant metagenomic gene catalog of ~2 × 106 microbial genes, 399 ARGs were identified in 131 gene types and conferred resistance to 47 antibiotics. Both the richness and diversity of the gut resistome were significantly reduced after the intervention. A total of 201 of the 399 ARGs were carried in 120 co-abundance gene groups (CAGs) directly binned from the gene catalog across both pre-and post-intervention samples. The intervention significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia, which were the major hubs for multiple resistance gene types. Thus, dietary intervention may become a potentially effective method for diminishing the gut resistome.
Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model
Authors: Zeng Xiaojun , Zhang Liyun , Xiao Xiuchan , Jiang Yuanyuan , Guo Yanzhi , Yu Xinyan , Pu Xuemei , Li Menglong 
Published: April 2016

AbstractThrombin-binding aptamer (TBA) with the sequence 5′GGTTGGTGTGGTTGG3′ could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.
Interplay of charge density wave and multiband superconductivity in 2H-PdxTaSe2
Authors: Bhoi D. , Khim S. , Nam W. , Lee B. S. , Kim Chanhee , Jeon B.-G. , Min B. H. , Park S. , Kim Kee Hoon 
Published: April 2016

Abstract2H-TaSe2 has been one of unique transition metal dichalcogenides exhibiting several phase transitions due to a delicate balance among competing electronic ground states. An unusual metallic state at high-T is sequentially followed by an incommensurate charge density wave (ICDW) state at ≈122 K and a commensurate charge density wave (CCDW) state at ≈90 K, and superconductivity at TC ~ 0.14 K. Upon systematic intercalation of Pd ions into TaSe2, we find that CCDW order is destabilized more rapidly than ICDW to indicate a hidden quantum phase transition point at x ~ 0.09–0.10. Moreover, TC shows a dramatic enhancement up to 3.3 K at x = 0.08, ~24 times of TC in 2H-TaSe2, in proportional to the density of states N(EF). Investigations of upper critical fields Hc2 in single crystals reveal evidences of multiband superconductivity as temperature-dependent anisotropy factor γH = "Equation missing", quasi-linear increase of "Equation missing", and an upward, positive-curvature in "Equation missing" near TC. Furthermore, analysis of temperature-dependent electronic specific heat corroborates the presence of multiple superconducting gaps. Based on above findings and electronic phase diagram vs x, we propose that the increase of N(EF) and effective electron-phonon coupling in the vicinity of CDW quantum phase transition should be a key to the large enhancement of TC in PdxTaSe2.