bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-140-5p inhibits hepatocellular carcinoma by directly targeting the unique isomerase Pin1 to block multiple cancer-driving pathways
Authors: Yan Xingxue , Zhu Zhendong , Xu Shenmin , Yang Li-nan , Liao Xin-Hua , Zheng Min , Yang Dayun , Wang Jichuang , Chen Dongmei , Wang Long , Liu Xiaolong , Liu Jingfeng , Chen Ruey-Hwa , Zhou Xiao Zhen , Lu Kun Ping , Liu Hekun 
Published: April 2017

AbstractHepatocellular carcinoma (HCC) is the second leading cause of cancer related-death. As a major common regulator of numerous cancer-driving pathways and a unique therapeutic target, the prolyl isomerase Pin1 is overexpressed in a majority of HCCs, whereas the mechanism underlying Pin1 overexpression remains elusive. Here we find that miR-140-5p inhibits HCC by directly targeting Pin1 to block multiple cancer-driving pathways. Bioinformatics analysis, miRNA binding and functional assays identify that miR-140-5p directly interacts with the 3′UTR of Pin1 and inhibits Pin1 translation. Furthermore, like stable Pin1 knockdown, moderate overexpression of miR-140-5p not only eliminates Pin1, but also inhibits cells growth and metastasis. Importantly, these effects of miR-140-5p are largely rescued by reconstitution of Pin1. Moreover, miR-140-5p inhibits multiple Pin1-dependent cancer pathways and suppresses tumor growth in mice. The clinical significance of these findings has been substantiated by the demonstrations that miR-140-5p is frequently down-regulated and inversely correlated with Pin1 overexpression in HCC tissues and cell lines. Given prevalent miR-140-5p downregulation in other cancers and major impact of Pin1 overexpression on activating numerous cancer-driving pathways including global miRNA downregulation, the miR-140-5p/Pin1 axis may play a major role in tumorigenesis and offer promising therapeutic targets for HCC and other cancers.
Serum Glycopatterns as Novel Potential Biomarkers for Diagnosis of Acute-on-Chronic Hepatitis B Liver Failure
Authors: Zhong Yaogang , Guo Yonghong , Liu Xiawei , Zhang Jiaxu , Ma Tianran , Shu Jian , Yang Jiajun , Zhang Jing , Jia Zhansheng , Li Zheng 
Published: April 2017

AbstractAcute-on-chronic hepatitis B liver failure (ACHBLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with cirrhosis, so little is known about the alterations of protein glycopatterns in serum with its development. We aimed to identify the alterations of serum glycopatterns in ACHBLF and probe the possibility of them as novel potential biomarkers for diagnosis of ACHBLF. As a result, there were 18 lectins (e.g., WFA, GSL-II, and PNA) to give significantly alterations of serum glycopatterns in ACHBLF compared with healthy controls (HC) (all p ≤ 0.0386). Meanwhile, among these lectins, there were 12 lectins (e.g., WFA, GAL-II, and EEL) also exhibited significantly alterations of serum glycopatterns in ACHBLF compared with HBV-infected chronic hepatitis (cHB) (all p ≤ 0.0252). The receiver-operating characteristic (ROC) curve analysis indicated there were 5 lectins (PHA-E + L, BS-I, ECA, ACA, and BPL) had the greatest discriminatory power for distinguishing ACHBLF and HC or cHB, respectively (all p ≤ 0.00136). We provided a new basic insight into serum glycopatterns in ACHBLF and investigated the correlation of alterations in serum glycopatterns as novel potential biomarkers for diagnosis of ACHBLF.
p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner
Authors: Cong Qian , Jia Hao , Li Ping , Qiu Shoutao , Yeh James , Wang Yibin , Zhang Zhen-Lin , Ao Junping , Li Baojie , Liu Huijuan 
Published: April 2017

AbstractBone mass is determined by the balance between bone formation, carried out by mesenchymal stem cell-derived osteoblasts, and bone resorption, carried out by monocyte-derived osteoclasts. Here we investigated the potential roles of p38 MAPKs, which are activated by growth factors and cytokines including RANKL and BMPs, in osteoclastogenesis and bone resorption by ablating p38α MAPK in LysM+monocytes. p38α deficiency promoted monocyte proliferation but regulated monocyte osteoclastic differentiation in a cell-density dependent manner, with proliferating p38α−/− cultures showing increased differentiation. While young mutant mice showed minor increase in bone mass, 6-month-old mutant mice developed osteoporosis, associated with an increase in osteoclastogenesis and bone resorption and an increase in the pool of monocytes. Moreover, monocyte-specific p38α ablation resulted in a decrease in bone formation and the number of bone marrow mesenchymal stem/stromal cells, likely due to decreased expression of PDGF-AA and BMP2. The expression of PDGF-AA and BMP2 was positively regulated by the p38 MAPK-Creb axis in osteoclasts, with the promoters of PDGF-AA and BMP2 having Creb binding sites. These findings uncovered the molecular mechanisms by which p38α MAPK regulates osteoclastogenesis and coordinates osteoclastogenesis and osteoblastogenesis.
Long-term treatment with intranasal insulin ameliorates cognitive impairment, tau hyperphosphorylation, and microglial activation in a streptozotocin-induced Alzheimer’s rat model
Authors: Guo Zhangyu , Chen Yanxing , Mao Yan-Fang , Zheng Tingting , Jiang Yasi , Yan Yaping , Yin Xinzhen , Zhang Baorong 
Published: April 2017

AbstractRecent evidence reveals that aberrant brain insulin signaling plays an important role in the pathology of Alzheimer’s disease (AD). Intranasal insulin administration has been reported to improve memory and attention in healthy participants and in AD patients. However, the underlying molecular mechanisms are poorly understood. Here, we treated intracerebroventricular streptozotocin-injected (ICV-STZ) rats, a commonly used animal model of sporadic AD, with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks and then studied their cognitive function with the Morris water maze test and biochemical changes via Western blotting. We observed cognitive deficits, tau hyperphosphorylation, and neuroinflammation in the brains of ICV-STZ rats. Intranasal insulin treatment for 6 weeks significantly improved cognitive function, attenuated the level of tau hyperphosphorylation, ameliorated microglial activation, and enhanced neurogenesis in ICV-STZ rats. Additionally, our results indicate that intranasal delivery of insulin probably attenuates tau hyperphosphorylation through the down-regulation of ERK1/2 and CaMKII in the brains of ICV-STZ rats. Our findings demonstrate a beneficial effect of intranasal insulin and provide the mechanistic basis for treating AD patients with intranasal insulin.
Phenotypic and genotypic correlation between myopia and intelligence
Authors: Williams Katie M. , Hysi Pirro G. , Yonova-Doing Ekaterina , Mahroo Omar A. , Snieder Harold , Hammond Christopher J. 
Published: April 2017

AbstractMyopia, or near-sightedness, is our most common eye condition and the prevalence is increasing globally. Visual impairment will occur if uncorrected, whilst high myopia causes sight-threatening complications. Myopia is associated with higher intelligence. As both are heritable, we set out to examine whether there is a genetic correlation between myopia and intelligence in over 1,500 subjects (aged 14–18 years) from a twin birth cohort. The phenotypic correlation between refractive error and intelligence was −0.116 (p < 0.01) - the inverse correlation due to the fact that myopia is a negative refractive error. Bivariate twin modeling confirmed both traits were heritable (refractive error 85%, intelligence 47%) and the genetic correlation was −0.143 (95% CI −0.013 to −0.273). Of the small phenotypic correlation the majority (78%) was explained by genetic factors. Polygenic risk scores were constructed based on common genetic variants identified in previous genome-wide association studies of refractive error and intelligence. Genetic variants for intelligence and refractive error explain some of the reciprocal variance, suggesting genetic pleiotropy; in the best-fit model the polygenic score for intelligence explained 0.99% (p = 0.008) of refractive error variance. These novel findings indicate shared genetic factors contribute significantly to the covariance between myopia and intelligence.
3D lattice distortions and defect structures in ion-implanted nano-crystals
Authors: Hofmann Felix , Tarleton Edmund , Harder Ross J. , Phillips Nicholas W. , Ma Pui-Wai , Clark Jesse N. , Robinson Ian K. , Abbey Brian , Liu Wenjun , Beck Christian E. 
Published: April 2017

AbstractFocussed Ion Beam (FIB) milling is a mainstay of nano-scale machining. By manipulating a tightly focussed beam of energetic ions, often gallium (Ga+), FIB can sculpt nanostructures via localised sputtering. This ability to cut solid matter on the nano-scale revolutionised sample preparation across the life, earth and materials sciences. Despite its widespread usage, detailed understanding of the FIB-induced structural damage, intrinsic to the technique, remains elusive. Here we examine the defects caused by FIB in initially pristine objects. Using Bragg Coherent X-ray Diffraction Imaging (BCDI), we are able to spatially-resolve the full lattice strain tensor in FIB-milled gold nano-crystals. We find that every use of FIB causes large lattice distortions. Even very low ion doses, typical of FIB imaging and previously thought negligible, have a dramatic effect. Our results are consistent with a damage microstructure dominated by vacancies, highlighting the importance of free-surfaces in determining which defects are retained. At larger ion fluences, used during FIB-milling, we observe an extended dislocation network that causes stresses far beyond the bulk tensile strength of gold. These observations provide new fundamental insight into the nature of the damage created and the defects that lead to a surprisingly inhomogeneous morphology.
Performance, stability and operation voltage optimization of screen-printed aqueous supercapacitors
Authors: Lehtimäki Suvi , Railanmaa Anna , Keskinen Jari , Kujala Manu , Tuukkanen Sampo , Lupo Donald 
Published: April 2017

AbstractHarvesting micropower energy from the ambient environment requires an intermediate energy storage, for which printed aqueous supercapacitors are well suited due to their low cost and environmental friendliness. In this work, a systematic study of a large set of devices is used to investigate the effect of process variability and operating voltage on the performance and stability of screen printed aqueous supercapacitors. The current collectors and active layers are printed with graphite and activated carbon inks, respectively, and aqueous NaCl used as the electrolyte. The devices are characterized through galvanostatic discharge measurements for quantitative determination of capacitance and equivalent series resistance (ESR), as well as impedance spectroscopy for a detailed study of the factors contributing to ESR. The capacitances are 200–360 mF and the ESRs 7.9–12.7 Ω, depending on the layer thicknesses. The ESR is found to be dominated by the resistance of the graphite current collectors and is compatible with applications in low-power distributed electronics. The effects of different operating voltages on the capacitance, leakage and aging rate of the supercapacitors are tested, and 1.0 V found to be the optimal choice for using the devices in energy harvesting applications.
High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles
Authors: Golub M. , Lehofer B. , Martinez N. , Ollivier J. , Kohlbrecher J. , Prassl R. , Peters J. 
Published: April 2017

AbstractLipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.
Lifetime imaging of GFP at CoxVIIIa reports respiratory supercomplex assembly in live cells
Authors: Rieger Bettina , Shalaeva Daria N. , Söhnel Anna-Carina , Kohl Wladislaw , Duwe Patrick , Mulkidjanian Armen Y. , Busch Karin B. 
Published: April 2017

AbstractThe assembly of respiratory complexes into macromolecular supercomplexes is currently a hot topic, especially in the context of newly available structural details. However, most work to date has been done with purified detergent-solubilized material and in situ confirmation is absent. We here set out to enable the recording of respiratory supercomplex formation in living cells. Fluorescent sensor proteins were placed at specific positions at cytochrome c oxidase suspected to either be at the surface of a CI1CIII2CIV1 supercomplex or buried within this supercomplex. In contrast to other loci, sensors at subunits CoxVIIIa and CoxVIIc reported a dense protein environment, as detected by significantly shortened fluorescence lifetimes. According to 3D modelling CoxVIIIa and CoxVIIc are buried in the CI1CIII2CIV1 supercomplex. Suppression of supercomplex scaffold proteins HIGD2A and CoxVIIa2l was accompanied by an increase in the lifetime of the CoxVIIIa-sensor in line with release of CIV from supercomplexes. Strikingly, our data provide strong evidence for defined stable supercomplex configuration in situ.
The global regulator Ncb2 escapes from the core promoter and impacts transcription in response to drug stress in Candida albicans
Authors: Shariq Mohd , Dhamgaye Sanjiveeni , Nair Remya , Goyal Neha , Jain Vaibhav , Mukhopadhyay Arnab , Mondal Alok K. , Mukhopadhyay Gauranga , Prasad Rajendra 
Published: April 2017

AbstractNcb2, the β subunit of NC2 complex, a heterodimeric regulator of transcription was earlier shown to be involved in the activated transcription of CDR1 gene in azole resistant isolate (AR) of Candida albicans. This study examines its genome-wide role by profiling Ncb2 occupancy between genetically matched pair of azole sensitive (AS) and AR clinical isolates. A comparison of Ncb2 recruitment between the two isolates displayed that 29 genes had higher promoter occupancy of Ncb2 in the AR isolate. Additionally, a host of genes exhibited exclusive occupancy of Ncb2 at promoters of either AR or AS isolate. The analysis also divulged new actors of multi-drug resistance, whose transcription was activated owing to the differential occupancy of Ncb2. The conditional, sequence-specific positional escape of Ncb2 from the core promoter in AS isolate and its preferential recruitment to the core promoter of certain genes in AR isolates was most noteworthy means of transcription regulation. Together, we show that positional rearrangement of Ncb2 resulting in either activation or repression of gene expression in response to drug-induced stress, represents a novel regulatory mechanism that opens new opportunities for therapeutic intervention to prevent development of drug tolerance in C. albicans cells.
Dynamic Default Mode Network across Different Brain States
Authors: Lin Pan , Yang Yong , Gao Junfeng , De Pisapia Nicola , Ge Sheng , Wang Xiang , Zuo Chun S. , Jonathan Levitt James , Niu Chen 
Published: April 2017

AbstractThe default mode network (DMN) is a complex dynamic network that is critical for understanding cognitive function. However, whether dynamic topological reconfiguration of the DMN occurs across different brain states, and whether this potential reorganization is associated with prior learning or experience is unclear. To better understand the temporally changing topology of the DMN, we investigated both nodal and global dynamic DMN-topology metrics across different brain states. We found that DMN topology changes over time and those different patterns are associated with different brain states. Further, the nodal and global topological organization can be rebuilt by different brain states. These results indicate that the post-task, resting-state topology of the brain network is dynamically altered as a function of immediately prior cognitive experience, and that these modulated networks are assembled in the subsequent state. Together, these findings suggest that the changing topology of the DMN may play an important role in characterizing brain states.
Transcriptome-based investigation of cirrus development and identifying microsatellite markers in rattan (Daemonorops jenkinsiana)
Authors: Zhao Hansheng , Sun Huayu , Li Lichao , Lou Yongfeng , Li Rongsheng , Qi Lianghua , Gao Zhimin 
Published: April 2017

AbstractRattan is an important group of regenerating non-wood climbing palm in tropical forests. The cirrus is an essential climbing organ and provides morphological evidence for evolutionary and taxonomic studies. However, limited data are available on the molecular mechanisms underlying the development of the cirrus. Thus, we performed in-depth transcriptomic sequencing analyses to characterize the cirrus development at different developmental stages of Daemonorops jenkinsiana. The result showed 404,875 transcripts were assembled, including 61,569 high-quality unigenes were identified, of which approximately 76.16% were annotated and classified by seven authorized databases. Moreover, a comprehensive analysis of the gene expression profiles identified differentially expressed genes (DEGs) concentrated in developmental pathways, cell wall metabolism, and hook formation between the different stages of the cirri. Among them, 37 DEGs were validated by qRT-PCR. Furthermore, 14,693 transcriptome-based microsatellites were identified. Of the 168 designed SSR primer pairs, 153 were validated and 16 pairs were utilized for the polymorphic analysis of 25 rattan accessions. These findings can be used to interpret the molecular mechanisms of cirrus development, and the developed microsatellites markers provide valuable data for assisting rattan taxonomy and expanding the understanding of genomic study in rattan.
Transition metal ions regulated oxygen evolution reaction performance of Ni-based hydroxides hierarchical nanoarrays
Authors: Zhou Tingting , Cao Zhen , Zhang Pan , Ma Houyi , Gao Zhen , Wang Heng , Lu Yue , He Jia , Zhao Yunfeng 
Published: April 2017

AbstractNickel-based hydroxide hierarchical nanoarrays (NiyM(OH)x HNAs M = Fe or Zn) are doped with non-noble transition metals to create nanostructures and regulate their activities for the oxygen evolution reaction. Catalytic performance in these materials depends on their chemical composition and the presence of nanostructures. These novel hierarchical nanostructures contain small secondary nanosheets that are grown on the primary nanowire arrays, providing a higher surface area and more efficient mass transport for electrochemical reactions. The activities of the NiyM(OH)x HNAs for the oxygen evolution reaction (OER) followed the order of Ni2.2Fe(OH)x > Ni(OH)2 > Ni2.1Zn(OH)x, and these trends are supported by density functional theory (DFT) calculations. The Fe-doped nickel hydroxide hierarchical nanoarrays (Ni2.2Fe(OH)x HNAs), which had an appropriate elemental composition and hierarchical nanostructures, achieve the lowest onset overpotential of 234 mV and the smallest Tafel slope of 64.3 mV dec−1. The specific activity, which is normalized to the Brunauer–Emmett–Teller (BET) surface area of the catalyst, of the Ni2.2Fe(OH)x HNAs is 1.15 mA cm−2BET at an overpotential of 350 mV. This is ~4-times higher than that of Ni(OH)2. These values are also superior to those of a commercial IrOx electrocatalyst.
Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages
Authors: Yang Jing-Xing , Hsieh Kou-Chou , Chen Yi-Ling , Lee Chien-Kuo , Conti Marco , Chuang Tsung-Hsien , Wu Chin-Pyng , Jin S.-L. Catherine 
Published: April 2017

AbstractActivation of TLR4 by lipopolysaccharide (LPS) induces both pro-inflammatory and anti-inflammatory cytokine production in macrophages. Type 4 phosphodiesterases (PDE4) are key cAMP-hydrolyzing enzymes, and PDE4 inhibitors are considered as immunosuppressors to various inflammatory responses. We demonstrate here that PDE4 inhibitors enhance the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) secretion in LPS-activated mouse peritoneal macrophages, and this response was regulated at the transcriptional level rather than an increased IL-1Ra mRNA stability. Studies with PDE4-deficient macrophages revealed that the IL-1Ra upregulation elicited by LPS alone is PKA-independent, whereas the rolipram-enhanced response was mediated by inhibition of only PDE4B, one of the three PDE4 isoforms expressed in macrophages, and it requires PKA but not Epac activity. However, both pathways activate CREB to induce IL-1Ra expression. PDE4B ablation also promoted STAT3 phosphorylation (Tyr705) to LPS stimulation, but this STAT3 activation is not entirely responsible for the IL-1Ra upregulation in PDE4B-deficient macrophages. In a model of LPS-induced sepsis, only PDE4B-deficient mice displayed an increased circulating IL-1Ra, suggesting a protective role of PDE4B inactivation in vivo. These findings demonstrate that PDE4B negatively modulates anti-inflammatory cytokine expression in innate immune cells, and selectively targeting PDE4B should retain the therapeutic benefits of nonselective PDE4 inhibitors.
Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer
Authors: Tan Guangguo , Wang Haibo , Yuan Jianlin , Qin Weijun , Dong Xin , Wu Hong , Meng Ping 
Published: April 2017

AbstractTo address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples.