bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53
Authors: Park E K , Lee J C , Park J W , Bang S Y , Yi S A , Kim B K , Park J H , Kwon S H , You J S , Nam S W , Cho E J , Han J W 
Published: November 2015

AbstractNovel therapeutic strategies are needed to overcome cancer recurrence, metastasis, and resistance to chemo- and radiotherapy. Cancer stem cells (CSCs) are major contributors to the malignant transformation of cells due to their capacity for self-renewal. Although various CSC markers have been identified in several types of tumors, they are primarily used as cancer-prediction markers and for the isolation of CSC populations. CD133, one of the best-characterized CSC markers in distinct solid tumor types, was shown to be correlated with CSC tumor-initiating capacity; however, the regulation of CD133 expression and its function in cancer are poorly understood. Here, we show that CD133 expression is negatively regulated by direct binding of the p53 tumor suppressor protein to a noncanonical p53-binding sequence in the CD133 promoter. Binding of p53 recruits Histone Deacetylase 1 (HDAC1) to the CD133 promoter and subsequently suppresses CD133 expression by reducing histone H3 acetylation. Furthermore, CD133 depletion suppresses tumor cell proliferation, colony formation, and the expression of core stemness transcription factors including NANOG, octamer-binding transcription factor 4 (OCT4), SOX2, and c-MYC. Critically, the anti-proliferative effects of p53 are antagonized by rescue of CD133 expression in a p53 overexpressing cell line, indicating that the tumor suppressive activity of p53 might be mediated by CD133 suppression. Taken together, our results suggest that p53-mediated transcriptional regulation of CD133 is a key underlying mechanism for controlling the growth and tumor-initiating capacity of CSCs and provide a novel perspective on targeting CSCs for cancer therapy.
L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer’s disease via activating dopamine D1 receptor/PKA signaling pathway
Authors: Hao J-R , Sun N , Lei L , Li X-Y , Yao B , Sun K , Hu R , Zhang X , Shi X-D , Gao C 
Published: November 2015

AbstractIt is accepted that amyloid β-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer’s disease (AD). However, there is still no effective treatment for preventing or reversing the progression of the disease. Targeting α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway.
The point mutation UCH-L1 C152A protects primary neurons against cyclopentenone prostaglandin-induced cytotoxicity: implications for post-ischemic neuronal injury
Authors: Liu H , Li W , Rose M E , Hickey R W , Chen J , Uechi G T , Balasubramani M , Day B W , Patel K V , Graham S H 
Published: November 2015

AbstractCyclopentenone prostaglandins (CyPGs), such as 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), are reactive prostaglandin metabolites exerting a variety of biological effects. CyPGs are produced in ischemic brain and disrupt the ubiquitin-proteasome system (UPS). Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a brain-specific deubiquitinating enzyme that has been linked to neurodegenerative diseases. Using tandem mass spectrometry (MS) analyses, we found that the C152 site of UCH-L1 is adducted by CyPGs. Mutation of C152 to alanine (C152A) inhibited CyPG modification and conserved recombinant UCH-L1 protein hydrolase activity after 15dPGJ2 treatment. A knock-in (KI) mouse expressing the UCH-L1 C152A mutation was constructed with the bacterial artificial chromosome (BAC) technique. Brain expression and distribution of UCH-L1 in the KI mouse was similar to that of wild type (WT) as determined by western blotting. Primary cortical neurons derived from KI mice were resistant to 15dPGJ2 cytotoxicity compared with neurons from WT mice as detected by the WST-1 cell viability assay and caspase-3 and poly ADP ribose polymerase (PARP) cleavage. This protective effect was accompanied with significantly less ubiquitinated protein accumulation and aggregation as well as less UCH-L1 aggregation in C152A KI primary neurons after 15dPGJ2 treatment. Additionally, 15dPGJ2-induced axonal injury was also significantly attenuated in KI neurons as compared with WT. Taken together, these studies indicate that UCH-L1 function is important in hypoxic neuronal death, and the C152 site of UCH-L1 has a significant role in neuronal survival after hypoxic/ischemic injury.
New Permian fauna from tropical Gondwana
Authors: Cisneros Juan C. , Marsicano Claudia , Angielczyk Kenneth D. , Smith Roger M. H. , Richter Martha , Fröbisch Jörg , Kammerer Christian F. , Sadleir Rudyard W. 
Published: November 2015

AbstractTerrestrial vertebrates are first known to colonize high-latitude regions during the middle Permian (Guadalupian) about 270 million years ago, following the Pennsylvanian Gondwanan continental glaciation. However, despite over 150 years of study in these areas, the biogeographic origins of these rich communities of land-dwelling vertebrates remain obscure. Here we report on a new early Permian continental tetrapod fauna from South America in tropical Western Gondwana that sheds new light on patterns of tetrapod distribution. Northeastern Brazil hosted an extensive lacustrine system inhabited by a unique community of temnospondyl amphibians and reptiles that considerably expand the known temporal and geographic ranges of key subgroups. Our findings demonstrate that tetrapod groups common in later Permian and Triassic temperate communities were already present in tropical Gondwana by the early Permian (Cisuralian). This new fauna constitutes a new biogeographic province with North American affinities and clearly demonstrates that tetrapod dispersal into Gondwana was already underway at the beginning of the Permian.
Targeting of SUMO substrates to a Cdc48–Ufd1–Npl4 segregase and STUbL pathway in fission yeast
Authors: Køhler Julie Bonne , Tammsalu Triin , Jørgensen Maria Mønster , Steen Nana , Hay Ronald Thomas , Thon Geneviève 
Published: November 2015

AbstractIn eukaryotes, the conjugation of proteins to the small ubiquitin-like modifier (SUMO) regulates numerous cellular functions. A proportion of SUMO conjugates are targeted for degradation by SUMO-targeted ubiquitin ligases (STUbLs) and it has been proposed that the ubiquitin-selective chaperone Cdc48/p97-Ufd1-Npl4 facilitates this process. However, the extent to which the two pathways overlap, and how substrates are selected, remains unknown. Here we address these questions in fission yeast through proteome-wide analyses of SUMO modification sites. We identify over a thousand sumoylated lysines in a total of 468 proteins and quantify changes occurring in the SUMO modification status when the STUbL or Ufd1 pathways are compromised by mutations. The data suggest the coordinated processing of several classes of SUMO conjugates, many dynamically associated with centromeres or telomeres. They provide new insights into subnuclear organization and chromosome biology, and, altogether, constitute an extensive resource for the molecular characterization of SUMO function and dynamics.
Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics: a post hoc analysis of the TIOSPIR trial
Authors: Wise Robert , Calverley Peter MA , Dahl Ronald , Dusser Daniel , Metzdorf Norbert , Müller Achim , Fowler Andy , Anzueto Antonio 
Published: November 2015

Abstract
Background:
Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects.

Aims:
The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 μg.

Methods:
A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease.

Results:
Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups.

Conclusions:
Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy.
Quantification of dislocation nucleation stress in TiN through high-resolution in situ indentation experiments and first principles calculations
Authors: Li N. , Yadav S.K. , Liu X.-Y. , Wang J. , Hoagland R.G. , Mara N. , Misra A. 
Published: November 2015

AbstractThrough in situ indentation of TiN in a high-resolution transmission electron microscope, the nucleation of full as well as partial dislocations has been observed from {001} and {111} surfaces, respectively. The critical elastic strains associated with the nucleation of the dislocations were analyzed from the recorded atomic displacements and the nucleation stresses corresponding to the measured critical strains were computed using density functional theory. The resolved shear stress was estimated to be 13.8 GPa for the partial dislocation 1/6 <110> {111} and 6.7 GPa for the full dislocation ½ <110> {110}. Such an approach of quantifying nucleation stresses for defects via in situ high-resolution experiment coupled with density functional theory calculation may be applied to other unit processes.
Strain-driven band inversion and topological aspects in Antimonene
Authors: Zhao Mingwen , Zhang Xiaoming , Li Linyang 
Published: November 2015

AbstractSearching for the two-dimensional (2D) topological insulators (TIs) with large bulk band gaps is the key to achieve room-temperature quantum spin Hall effect (QSHE). Using first-principles calculations, we demonstrated that the recently-proposed antimonene [Zhang et al., Angew. Chem. Int. Ed. 54, 3112–3115 (2015)] can be tuned to a 2D TI by reducing the buckling height of the lattice which can be realized under tensile strain. The strain-driven band inversion in the vicinity of the Fermi level is responsible for the quantum phase transition. The buckled configuration of antimonene enables it to endure large tensile strain up to 18% and the resulted bulk band gap can be as large as 270 meV. The tunable bulk band gap makes antimonene a promising candidate material for achieving quantum spin Hall effect (QSH) at high temperatures which meets the requirement of future electronic devices with low power consumption.
MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a
Authors: Du Jinghua , Niu Xuemin , Wang Yang , Kong Lingbo , Wang Rongqi , Zhang Yuguo , Zhao Suxian , Nan Yuemin 
Published: November 2015

AbstractNonalcoholic fibrosing steatohepatitis is a uniform process throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been suggested to modulate cellular processes in liver diseases. However, the functional role of miRNAs in nonalcoholic fibrosing steatohepatitis is largely unclear. In this study, we systematically analyzed the hepatic miRNAs by microarray analysis in nonalcoholic fibrosing steatohepatitis in C57BL/6J mice induced by methionine-choline deficient (MCD) diet. We identified 19 up-regulated and 18 down-regulated miRNAs in liver with fibrosis. Among these dysregulated miRNAs, miR-146a-5p was the most significant down-regulated miRNA. Luciferase activity assay confirmed that Wnt1 and Wnt5a were both the target genes of miR-146a-5p. Hepatic miR-146a-5p was down-regulated in fibrosing steatohepatitis, but its target genes Wnt1 and Wnt5a and their consequent effectors α-SMA and Col-1 were significantly up-regulated. In addition, miR-146a-5p was downregulated, whilst Wnt1 and Wnt5a were up-regulated in the activated primary hepatic stellate cells (HSCs) compared to the quiescent primary HSCs. Overexpression of miR-146a-5p in HSCs inhibited HSC activation and proliferation, which concomitant with the decreased expressions of Wnt1, Wnt5a, α-SMA and Col-1. In conclusion, miR-146a-5p suppresses activation and proliferation of HSCs in the progress of nonalcoholic fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and consequent effectors α-SMA and Col-1.
Molecular changes in the medial prefrontal cortex and nucleus accumbens are associated with blocking the behavioral sensitization to cocaine
Authors: Zhang Yi , Zhu Xiongzhao , Huang Can , Zhang Xiuwu 
Published: November 2015

AbstractPrevious studies have demonstrated that cocaine-induced behavioral sensitization is associated with persistent functional and structural alterations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc); however, the molecular mechanisms underlying these changes have not been elucidated. In this study, the behavioral sensitization to cocaine was established in Sprague Dawley rats and was measured by locomotion and behavioral rating. The brain tissue homogenization was used for measuring the level of brain-derived neurotrophic factor (BDNF), the expression and activity of integrin-linked kinase (ILK), level of protein kinase B (Akt) phosphorylation at serine 473 and threonine 308 and the expression of p75NTR, TrkA and TrkB protein. The Results showed that cocaine sensitization was associated with increased BDNF, ILK activity, phospho-Akt Ser473, p75NTR and TrkB protein levels in the mPFC and NAc core. The combination of pergolide and ondansetron normalized not only behavioral sensitization, but also the increases in these molecular markers. Dual immunofluoresence staining showed that ILK expression is co-distributed with p75NTR and TrkA expression in both the mPFC and NAc core. Results suggested that the BDNF-TrkA/p75NTR-ILK-Akt signaling pathway may be active in cocaine sensitization and associated neural plasticity in the mPFC and NAc core.
Subclinical decelerations during developing hypotension in preterm fetal sheep after acute on chronic lipopolysaccharide exposure
Authors: Lear Christopher A. , Davidson Joanne O. , Galinsky Robert , Yuill Caroline A. , Wassink Guido , Booth Lindsea C. , Drury Paul P. , Bennet Laura , Gunn Alistair J. 
Published: November 2015

AbstractSubclinical (shallow) heart rate decelerations occur during neonatal sepsis, but there is limited information on their relationship with hypotension or whether they occur before birth. We examined whether subclinical decelerations, a fall in fetal heart rate (FHR) that remained above 100 bpm, were associated with hypotension in preterm fetal sheep exposed to lipopolysaccharide (LPS). Chronically-instrumented fetal sheep at 0.7 gestation received continuous low-dose LPS infusions (n = 15, 100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h) or saline (n = 8). Boluses of 1 μg LPS or saline were given at 48 and 72 h. FHR variability (FHRV) was calculated and sample asymmetry was used to assess the severity and frequency of decelerations. Low-dose LPS infusion did not affect FHR. After the first LPS bolus, 7 fetuses remained normotensive, while 8 developed hypotension (a fall in mean arterial blood pressure of ≥5 mmHg). Developing hypotension was associated with subclinical decelerations, with a corresponding increase in sample asymmetry and FHRV (p < 0.05). The second LPS bolus was associated with similar but attenuated changes in FHR and blood pressure (p < 0.05). In conclusion, subclinical decelerations are not consistently seen during prenatal exposure to LPS, but may be a useful marker of developing inflammation-related hypotension before birth.
Genotype-dependent lifespan effects in peptone deprived Caenorhabditis elegans
Authors: Stastna Jana J. , Snoek L. Basten , Kammenga Jan E. , Harvey Simon C. 
Published: November 2015

AbstractDietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan. There have however been reports in many systems of cases where restricted food intake either shortens, or does not affect, lifespan. Here we analyze lifespan and the effect of food restriction via deprived peptone levels on lifespan in wild isolates and introgression lines (ILs) of the nematode Caenorhabditis elegans. These analyses identify genetic variation in lifespan, in the effect of this variation in diet on lifespan and also in the likelihood of maternal, matricidal, hatching. Importantly, in the wild isolates and the ILs, we identify genotypes in which peptone deprivation mediated dietary restriction reduces lifespan. We also identify, in recombinant inbred lines, a locus that affects maternal hatching, a phenotype closely linked to dietary restriction in C. elegans. These results indicate that peptone deprivation mediated dietary restriction affects lifespan in C. elegans in a genotype-dependent manner, reducing lifespan in some genotypes. This may operate by a mechanism similar to dietary restriction.
Homogeneous fluorescent specific PCR for the authentication of medicinal snakes using cationic conjugated polymers
Authors: Jiang Chao , Yuan Yuan , Liu Libing , Hou Jingyi , Jin Yan , Huang Luqi 
Published: November 2015

AbstractA label-free, homogenous and sensitive one-step method for the molecular authentication of medicinal snakes has been developed by combining a rapid PCR technique with water-soluble cationic conjugated polyelectrolytes (CCPs). Three medicinal snake materials (Deinagkistrodon acutus, Zaocys dhumnades and Bungarus multicinctus; a total of 35 specimens) and 48 snake specimens with similar morphologies and textures were clearly distinguished by the naked eye by utilizing a CCP-based assay in a high-throughput manner. The identification of medicinal snakes in patented Chinese drugs was successfully performed using this detection system. In contrast to previous fluorescence-labeled oligonucleotide detection and direct DNA stain hybridization assays, this method does not require designing dye-labeled primers and unfavorable dimer fluorescence is avoided in this homogenous method.
Integrated Genome-wide association and hypothalamus eQTL studies indicate a link between the circadian rhythm-related gene PER1 and coping behavior
Authors: Ponsuksili Siriluck , Zebunke Manuela , Murani Eduard , Trakooljul Nares , Krieter Joachim , Puppe Birger , Schwerin Manfred , Wimmers Klaus 
Published: November 2015

AbstractAnimal personality and coping styles are basic concepts for evaluating animal welfare. Struggling response of piglets in so-called backtests early in life reflects their coping strategy. Behavioral reactions of piglets in backtests have a moderate heritability, but their genetic basis largely remains unknown. Here, latency, duration and frequency of struggling attempts during one-minute backtests were repeatedly recorded of piglets at days 5, 12, 19 and 26. A genome-wide association study for backtest traits revealed 465 significant SNPs (FDR ≤ 0.05) mostly located in QTL (quantitative trait locus) regions on chromosome 3, 5, 12 and 16. In order to capture genes in these regions, 37 transcripts with significant SNPs were selected for expressionQTL analysis in the hypothalamus. Eight genes (ASGR1, CPAMD8, CTC1, FBXO39, IL19, LOC100511790, RAD51B, UBOX5) had cis- and five (RANGRF, PER1, PDZRN3, SH2D4B, LONP2) had trans-expressionQTL. In particular, for PER1, with known physiological implications for maintenance of circadian rhythms, a role in coping behavior was evidenced by confirmed association in an independent population. For CTC1 a cis-expression QTL and the consistent relationship of gene polymorphism, mRNA expression level and backtest traits promoted its link to coping style. GWAS and eQTL analyses uncovered positional and functional gene candidates for coping behavior.
Molecular dynamics investigations of mechanical behaviours in monocrystalline silicon due to nanoindentation at cryogenic temperatures and room temperature
Authors: Du Xiancheng , Zhao Hongwei , Zhang Lin , Yang Yihan , Xu Hailong , Fu Haishuang , Li Lijia 
Published: November 2015

AbstractMolecular dynamics simulations of nanoindentation tests on monocrystalline silicon (010) surface were conducted to investigate the mechanical properties and deformation mechanism from cryogenic temperature being 10 K to room temperature being 300 K. Furthermore, the load-displacement curves were obtained and the phase transformation was investigated at different temperatures. The results show that the phase transformation occurs both at cryogenic temperatures and at room temperature. By searching for the presence of the unique non-bonded fifth neighbour atom, the metastable phases (Si-III and Si-XII) with fourfold coordination could be distinguished from Si-I phase during the loading stage of nanoindentation process. The Si-II, Si-XIII and amorphous phase were also found in the region beneath the indenter. Moreover, through the degree of alignment of the metastable phases along specific crystal orientation at different temperatures, it was found that the temperature had effect on the anisotropy of the monocrystalline silicon and the simulation results indicate that the anisotropy of monocrystalline silicon is strengthened at low temperatures.