bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Bag-1 inhibitor, Thio-2, reverses an atypical 3D morphology driven by Bag-1L overexpression in a MCF-10A model of ductal carcinoma in situ
Authors: Papadakis E S , Barker C R , Syed H , Reeves T , Schwaiger S , Stuppner H , Troppmair J , Blaydes J P , Cutress R I 
Published: April 2016

AbstractMammary MCF-10A cells seeded on reconstituted basement membrane form spherical structures with a hollow central lumen, termed acini, which are a physiologically relevant model of mammary morphogenesis. Bcl-2-associated athanogene 1 (Bag-1) is a multifunctional protein overexpressed in breast cancer and ductal carcinoma in situ. When present in the nucleus Bag-1 is predictive of clinical outcome in breast cancer. Bag-1 exists as three main isoforms, which are produced by alternative translation initiation from a single mRNA. The long isoform of Bag-1, Bag-1L, contains a nuclear localisation sequence not present in the other isoforms. When present in the nucleus Bag-1L, but not the other Bag-1 isoforms, can interact with and modulate the activities of estrogen-, androgen- and vitamin D-receptors. Overexpression of Bag-1 mRNA in MCF-10A is known to produce acini with luminal filling reminiscent of ductal carcinoma in situ. As this mRNA predominantly overexpresses the short isoform of Bag-1, Bag-1S, we set out to examine whether the nuclear Bag-1L isoform is sufficient to drive premalignant change by developing a Bag-1L-overexpressing MCF-10A model. Two clones differentially overexpressing Bag-1L were grown in two-dimensional (2D) and three-dimensional (3D) cultures and compared with an established model of HER2-driven transformation. In 2D cultures, Bag-1L overexpression reduced proliferation but did not affect growth factor responsiveness or clonogenicity. Acini formed by Bag-1L-overexpressing cells exhibited reduced luminal clearing when compared with controls. An abnormal branching morphology was also observed which correlated with the level of Bag-1L overexpression, suggesting further malignant change. Treatment with Thio-2, a small-molecule inhibitor of Bag-1, reduced the level of branching. In summary, 3D cultures of MCF-10A mammary epithelial cells overexpressing Bag-1L demonstrate a premalignant phenotype with features of ductal carcinoma in situ. Using this model to test the small-molecule Bag-1 inhibitor, Thio-2, reveals its potential to reverse the atypical branched morphology of acini that characterizes this premalignant change.
CD55 is a HIF-2α marker with anti-adhesive and pro-invading properties in neuroblastoma
Authors: Cimmino F , Avitabile M , Pezone L , Scalia G , Montanaro D , Andreozzi M , Terracciano L , Iolascon A , Capasso M 
Published: April 2016

AbstractCD55 has been revealed to have an important role in tumor genesis, and presence of small populations of cells with strong CD55 expression would be sufficient to predict poor prognosis of several tumors. In our study we revealed that CD55 is a novel target of hypoxia-inducible factor HIF-2α in neuroblastoma (NB) cells. We show that HIF-2α expression is sufficient to sustain stem-like features of NB cells, whereas CD55 protein upon HIF-2α expression contributes to growth of colonies and to invasion of cells, but not to stemness features. Interestingly, in NB tissues, CD55 expression is limited to quite a small population of cells that are HIF-2α positive, and the gene expression of CD55 in the NB data set reveals that the presence of CD55high affects prognosis of NB patients. The functional characterization of CD55-positive populations within heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti-adhesive properties that might provide the basis for the ability of solid tumors to survive as microscopic residual disease. The easy accessibility to CD55 membrane antigen will offer the possibility of a novel antibody approach in the treatment of recurrent tumors and will provide a ready target for antibody-based visualization in NB diagnosis and prognosis.
MicroRNA-206 is differentially expressed in Brca1-deficient mice and regulates epithelial and stromal cell compartments of the mouse mammary gland
Authors: Wronski A , Sandhu G K , Milevskiy M J G , Brewster B L , Bridge J A , Shewan A M , Edwards S L , French J D , Brown M A 
Published: April 2016

AbstractDepletion of Brca1 leads to defects in mouse mammary gland development and mammary tumors in humans and mice. To explore the role of microRNAs (miRNAs) in this process, we examined the mammary glands of MMTV-Cre Brca1Co/Co mice for differential miRNA expression using a candidate approach. Several miRNAs were differentially expressed in mammary tissue at day 1 of lactation and in mammary epithelial cell lines in which Brca1 messenger RNA (mRNA) levels have been reduced. Functional studies revealed that several of these miRNAs regulate mammary epithelial cell function in vitro, including miR-206. Creation and analysis of MMTV-miR-206 transgenic mice showed no effect on lactational mammary development and no tumors, but indicates a role in mammary tissue remodeling in mature mice, potentially involving Igf-1 and Sfrp1. These results indicate the potential of miRNAs to mediate the consequences of Brca1 loss and suggest a novel function for miR-206.
Overconfidence, Incentives and Digit Ratio
Authors: Neyse Levent , Bosworth Steven , Ring Patrick , Schmidt Ulrich 
Published: April 2016

AbstractThis paper contributes to a better understanding of the biological underpinnings of overconfidence by analyzing performance predictions in the Cognitive Reflection Test with and without monetary incentives. In line with the existing literature we find that the participants are too optimistic about their performance on average; incentives lead to higher performance; and males score higher than females on this particular task. The novelty of this paper is an analysis of the relation between participants’ performance prediction accuracy and their second to fourth digit ratio. It has been reported that the digit ratio is a negatively correlated bio-marker of prenatal testosterone exposure. In the un-incentivized treatment, we find that males with low digit ratios, on average, are significantly more overconfident about their performance. In the incentivized treatment, however, we observe that males with low digit ratios, on average, are less overconfident about their performance. These effects are not observed in females. We discuss how these findings fit into the literature on testosterone and decision making and how they might help to explain seemingly opposing evidence.
BitterX: a tool for understanding bitter taste in humans
Authors: Huang Wenkang , Shen Qiancheng , Su Xubo , Ji Mingfei , Liu Xinyi , Chen Yingyi , Lu Shaoyong , Zhuang Hanyi , Zhang Jian 
Published: April 2016

AbstractBitterX is an open-access tool aimed at providing a platform for identifying human bitter taste receptors, TAS2Rs, for small molecules. It predicts TAS2Rs from the molecular structures of arbitrary chemicals by integrating two individual functionalities: bitterant verification and TAS2R recognition. Using BitterX, several novel bitterants and their receptors were predicted and experimentally validated in the study. Therefore, BitterX may be an effective method for deciphering bitter taste coding and could be a useful tool for both basic bitter research in academia and new bitterant discoveries in the industry.
Aquatic vegetation in response to increased eutrophication and degraded light climate in Eastern Lake Taihu: Implications for lake ecological restoration
Authors: Zhang Yunlin , Liu Xiaohan , Qin Boqiang , Shi Kun , Deng Jianming , Zhou Yongqiang 
Published: April 2016

AbstractTerrestrial and aquatic ecosystem degradation is widely recognized as a major global environmental and development problem. Although great efforts have been made to prevent aquatic ecosystem degradation, the degree, extent and impacts of this phenomenon remain controversial and unclear, such as its driving mechanisms. Here, we present results from a 17-year field investigation (1998–2014) of water quality and a 12-year remote sensing mapping (2003–2014) of the aquatic vegetation presence frequency (VPF) in Eastern Lake Taihu, a macrophyte-dominated bay of Lake Taihu in China. In the past 17 years, nutrient concentrations and water level (WL) have significantly increased, but the Secchi disk depth (SDD) has significantly decreased. These changes were associated with increased lake eutrophication and a degraded underwater light climate that further inhibited the growth of aquatic vegetation. In Eastern Lake Taihu, increased nutrients, chlorophyll a and WL, and a decreased SDD were all significantly correlated with a decreased VPF. NH4+-N concentration and SDD/WL were the most important controlling factors for VPF. Therefore, increased anthropogenic nutrient inputs and a degraded underwater light climate surely result in a decreased VPF. These results elucidate the driving mechanism of aquatic vegetation degradation and will facilitate Lake Taihu ecological restoration.
Identification of genes associated with the astrocyte-specific gene Gfap during astrocyte differentiation
Authors: Ito Kenji , Sanosaka Tsukasa , Igarashi Katsuhide , Ideta-Otsuka Maky , Aizawa Akira , Uosaki Yuichi , Noguchi Azumi , Arakawa Hirokazu , Nakashima Kinichi , Takizawa Takumi 
Published: April 2016

AbstractChromosomes and genes are non-randomly arranged within the mammalian cell nucleus and gene clustering is of great significance in transcriptional regulation. However, the relevance of gene clustering and their expression during the differentiation of neural precursor cells (NPCs) into astrocytes remains unclear. We performed a genome-wide enhanced circular chromosomal conformation capture (e4C) to screen for genes associated with the astrocyte-specific gene glial fibrillary acidic protein (Gfap) during astrocyte differentiation. We identified 18 genes that were specifically associated with Gfap and expressed in NPC-derived astrocytes. Our results provide additional evidence for the functional significance of gene clustering in transcriptional regulation during NPC differentiation.
Some pitfalls in application of functional data analysis approach to association studies
Authors: Svishcheva G. R. , Belonogova N. M. , Axenovich T. I. 
Published: April 2016

AbstractOne of the most effective methods for gene-based mapping employs functional data analysis, which smoothes data using standard basis functions. The full functional linear model includes a functional representation of genotypes and their effects, while the beta-smooth only model smoothes the genotype effects only. Benefits and limitations of the beta-smooth only model should be studied before using it in practice. Here we analytically compare the full and beta-smooth only models under various scenarios. We show that when the full model employs two sets of basis functions equal in type and number, genotypes smoothing is eliminated from the model and it becomes analytically equivalent to the beta-smooth only model. If the basis functions differ only in type, genotypes smoothing is also eliminated from the full model, but the type of basis functions used for smoothing genotype effects becomes redefined. This leads to misinterpretation of the results and may reduce statistical power. When basis functions differ in number, no analytical comparison of the full and beta-smooth only models is possible. However, we show that the numbers of basis functions set unequal can become equal during the analysis and the full model becomes disadvantageous.
CD300c is uniquely expressed on CD56bright Natural Killer Cells and differs from CD300a upon ligand recognition
Authors: Dimitrova Milena , Zenarruzabeitia Olatz , Borrego Francisco , Simhadri Venkateswara R. 
Published: April 2016

AbstractPaired receptors on NK cells recognize similar ligands with varied strength of binding ability and perform different functions. The CD300 molecules are emerging as novel immune regulators in health and disease due to their interaction with their lipid-nature ligands. Particularly, the paired receptors CD300c and CD300a have been shown to elicit activating and inhibitory capabilities, respectively. In the current study, we seek to investigate the expression and function of CD300c on human NK cells. We demonstrate that IL-2 and IL-15 treatment significantly induce CD300c expression exclusively on CD56bright NK cells. CD300c up-regulation requires STAT5 and its expression is inhibited by IL-4. Consistently, IL-2 secreted from activated CD4+ T cells specifically induces the expression of CD300c on CD56bright NK cells. Crosslinking CD300c with a specific antibody enhances the proficiency of CD56bright NK cells to degranulate and induce chemokine and cytokine secretion. We also show the differential binding of CD300a and CD300c to their ligands phosphatidylethanolamine (PE) and phosphatidylserine (PS) and their differential ability to affect CD56bright NK cell functions. Our results provide an insight into the novel set of paired receptors CD300a and CD300c that are distinctively expressed on CD56bright NK cells with varied effector functions.
A novel non-canonical Notch signaling regulates expression of synaptic vesicle proteins in excitatory neurons
Authors: Hayashi Yukari , Nishimune Hiroshi , Hozumi Katsuto , Saga Yumiko , Harada Akihiro , Yuzaki Michisuke , Iwatsubo Takeshi , Kopan Raphael , Tomita Taisuke 
Published: April 2016

AbstractNotch signaling plays crucial roles for cellular differentiation during development through γ-secretase-dependent intramembrane proteolysis followed by transcription of target genes. Although recent studies implicate that Notch regulates synaptic plasticity or cognitive performance, the molecular mechanism how Notch works in mature neurons remains uncertain. Here we demonstrate that a novel Notch signaling is involved in expression of synaptic proteins in postmitotic neurons. Levels of several synaptic vesicle proteins including synaptophysin 1 and VGLUT1 were increased when neurons were cocultured with Notch ligands-expressing NIH3T3 cells. Neuron-specific deletion of Notch genes decreased these proteins, suggesting that Notch signaling maintains the expression of synaptic vesicle proteins in a cell-autonomous manner. Unexpectedly, cGMP-dependent protein kinase (PKG) inhibitor, but not γ-secretase inhibitor, abolished the elevation of synaptic vesicle proteins, suggesting that generation of Notch intracellular domain is dispensable for this function. These data uncover a ligand-dependent, but γ-secretase-independent, non-canonical Notch signaling involved in presynaptic protein expression in postmitotic neurons.
Kurtosis fractional anisotropy, its contrast and estimation by proxy
Authors: Hansen Brian , Jespersen Sune Nørhøj 
Published: April 2016

AbstractThe diffusion kurtosis observed with diffusion magnetic resonance imaging (dMRI) may vary with direction. This directional variation is summarized in the scalar kurtosis fractional anisotropy (KFA). Recent studies suggest that kurtosis anisotropy offers microstructural contrast not contained in other commonly used dMRI markers. We compare KFA to other dMRI contrasts in fixed rat brain and in human brain. We then investigate the observed contrast differences using data obtained in a physical phantom and simulations based on data from the phantom, rat spinal cord, and human brain. Lastly, we assess a strategy for rapid estimation of a computationally modest KFA proxy by evaluating its correlation to true KFA for varying number of sampling directions and signal-to-noise ratio (SNR) levels. We also map this proxy’s b-value dependency. We find that KFA supplements the contrast of other dMRI metrics – particularly fractional anisotropy (FA) which vanishes in near orthogonal fiber arrangements where KFA does not. Simulations and phantom data support this interpretation. KFA therefore supplements FA and could be useful for evaluation of complex tissue arrangements. The KFA proxy is strongly correlated to true KFA when sampling is performed along at least nine directions and SNR is high.
Diastereomeric resolution directed towards chirality determination focussing on gas-phase energetics of coordinated sodium dissociation
Authors: Kanie Osamu , Shioiri Yuki , Ogata Koji , Uchida Waka , Daikoku Shusaku , Suzuki Katsuhiko , Nakamura Shinichiro , Ito Yukishige 
Published: April 2016

AbstractDefining chiral centres is addressed by introducing a pair of chiral auxiliary groups. Ions of diastereomeric pairs of molecules could be distinguished utilising energy-resolved mass spectrometry, and the applicability of the method to a series of compounds carrying amine, carboxylic acid, alcohol, and all the amino acids was verified. The method was further strengthened by distinguishing diastereomeric ions that did not undergo fragmentation. Mass spectrometric evaluation of the dissociation process of adducted sodium cations from the diastereomeric precursors agreed with the theoretical calculations, indicating the potential usefulness of the method for the determination of absolute configurations.
The atmospheric electrical index for ENSO modoki: Is ENSO modoki one of the factors responsible for the warming trend slowdown?
Authors: Kulkarni Madhuri N. , Siingh Devendraa 
Published: April 2016

AbstractLike the southern oscillation index (SOI) based on the pressure difference between Tahiti (17.5°S, 150°W) and Darwin (12.5°S, 130°E), we propose the new atmospheric electrical index (AEI) taking the difference in the model calculated atmospheric electrical columnar resistance (Rc) which involves planetary boundary layer height (PBLH) and aerosol concentration derived from the satellite measurements. This is the first non-oceanic index capable of differentiating between the conventional and modoki La Niña and El Niño both and may be useful in the future air-sea coupling studies and as a complementary to the oceanic indices. As the PBLH variation over Darwin is within 10% of its long term mean, a strong rise in the Rc over Darwin during the modoki period supports modoki’s connection with aerosol loading. Our correlation results show that the intensity of El Niño (La Niña) event is almost independent (not independent) of its duration and the possibility of ENSO modoki being one of the factors responsible for the warming trend slowdown (WTS).
Phylogenetic analysis of β-xylanase SRXL1 of Sporisorium reilianum and its relationship with families (GH10 and GH11) of Ascomycetes and Basidiomycetes
Authors: Álvarez-Cervantes Jorge , Díaz-Godínez Gerardo , Mercado-Flores Yuridia , Gupta Vijai Kumar , Anducho-Reyes Miguel Angel 
Published: April 2016

AbstractIn this paper, the amino acid sequence of the β-xylanase SRXL1 of Sporisorium reilianum, which is a pathogenic fungus of maize was used as a model protein to find its phylogenetic relationship with other xylanases of Ascomycetes and Basidiomycetes and the information obtained allowed to establish a hypothesis of monophyly and of biological role. 84 amino acid sequences of β-xylanase obtained from the GenBank database was used. Groupings analysis of higher-level in the Pfam database allowed to determine that the proteins under study were classified into the GH10 and GH11 families, based on the regions of highly conserved amino acids, 233–318 and 180–193 respectively, where glutamate residues are responsible for the catalysis.
Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans
Authors: Zhao Yunli , Yang Ruilong , Rui Qi , Wang Dayong 
Published: April 2016

AbstractGraphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.
Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system
Authors: Yuan Hong-Jie , Han Xiao , He Nan , Wang Guo-Liang , Gong Shuai , Lin Juan , Gao Min , Tan Jing-He 
Published: April 2016

AbstractPrevious studies indicate that stress damages oocytes with increased secretion of glucorticoids. However, although injection of female mice with cortisol decreased oocyte competence, exposure of mouse oocytes directly to physiological or stress-induced concentrations of glucorticoids did not affect oocyte maturation and embryo development. This study has explored the mechanisms by which glucocorticoids impair oocyte competence. Female mice were injected with cortisol and the effects of cortisol-injection on oocyte competence, ovarian cell apoptosis and Fas/FasL activation were observed. The results showed that cortisol-injection decreased (a) oocyte developmental potential, (b) the E2/P4 ratio in serum and ovaries, and (c) expression of insulin-like growth factor 1, brain-derived neurotrophic factor and glucocorticoid receptor in mural granulosa cells (MGCs), while increasing levels of (a) cortisol in serum and ovaries, (b) apoptosis in MGCs and cumulus cells (CCs), (c) FasL secretion in ovaries and during oocyte maturation in vitro, and (d) Fas in MGCs, CCs and oocytes. The detrimental effects of cortisol-injection on oocyte competence and apoptosis of MGCs and CCs were significantly relieved when the gld (generalized lymphoproliferative disorder) mice harboring FasL mutations were observed. Together, the results suggested that glucocorticoids impair oocyte competence by triggering apoptosis of ovarian cells via activating the Fas system.