bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-9, miR-153 and miR-124 are down-regulated by acute exposure to cocaine in a dopaminergic cell model and may contribute to cocaine dependence
Authors: Cabana-Domínguez Judit , Arenas Concepció , Cormand Bru , Fernàndez-Castillo Noèlia 
Published: August 2018

AbstractCocaine is one of the most used psychostimulant drugs worldwide. MicroRNAs are post-transcriptional regulators of gene expression that are highly expressed in brain, and several studies have shown that cocaine can alter their expression. In a previous study, we identified several protein-coding genes that are differentially expressed in a dopaminergic neuron-like model after an acute exposure to cocaine. Now, we used the prediction tool WebGestalt to identify miRNA molecules potentially involved in the regulation of these genes. Using the same cellular model, we found that seven of these miRNAs are down-regulated by cocaine: miR-124-3p, miR-124-5p, miR-137, miR-101-3p, miR-9-5p, miR-369-3p and miR-153-3p, the last three not previously related to cocaine. Furthermore, we found that three of the miRNA genes that are differentially expressed in our model (hsa-miR-9-1, hsa-miR-153-1 and hsa-miR-124-3) are nominally associated with cocaine dependence in a case–control study (2,085 cases and 4,293 controls). In summary, we highlighted novel miRNAs that may be involved in those cocaine-induced changes of gene expression that underlie addiction. Moreover, we identified genetic variants that contribute to cocaine dependence in three of these miRNA genes, supporting the idea that genes differentially expressed under cocaine may play an important role in the susceptibility to cocaine dependence.
SIRT2 is required for efficient reprogramming of mouse embryonic fibroblasts toward pluripotency
Authors: Kim Ah-Young , Lee Eun-Mi , Lee Eun-Joo , Kim Jae-Hong , Suk Kyoungho , Lee Eunhye , Hur Keun , Hong Yean Ju , Do Jeong Tae , Park SunYoung , Jeong Kyu-Shik 
Published: August 2018

AbstractThe role of sirtuins (SIRTs) in cancer biology has been the focus of recent research. The similarities between underlying pathways involved in the induction of pluripotent stem cells and transformation of cancer cells revealed the role of SIRTs in cellular reprogramming. Seven SIRTs have been identified in mammals and downregulation of SIRT2 was found to facilitate the generation of primed pluripotent stem cells, such as human induced pluripotent stem cells. Herein, we evaluated the role of SIRT2 in naive pluripotent stem cell generation using murine cells. We found that absolute depletion of SIRT2 in mouse embryonic fibroblasts resulted in a notable reduction in reprogramming efficiency. SIRT2 depletion not only upregulated elements of the INK4/ARF locus, which in turn had an antiproliferative effect, but also significantly altered the expression of proteins related to the PI3K/Akt and Hippo pathways, which are important signaling pathways for stemness. Thus, this study demonstrated that SIRT2 is required for cellular reprogramming to naive states of pluripotency in contrast to primed pluripotency states.
MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors
Authors: Petroni Marialaura , Sardina Francesca , Infante Paola , Bartolazzi Armando , Locatelli Erica , Fabretti Francesca , Di Giulio Stefano , Capalbo Carlo , Cardinali Beatrice , Coppa Anna , Tessitore Alessandra , Colicchia Valeria , Sahùn Roncero Maria , Belardinilli Francesca , Di Marcotullio Lucia , Soddu Silvia , Comes Franchini Mauro , Petricci Elena , Gulino Alberto , Giannini Giuseppe 
Published: August 2018

AbstractMRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells. MYCN activation, often due to genetic amplification, represents the driving oncogenic event for a number of human tumors, conferring bad prognosis and predicting very poor responses even to the most aggressive therapeutic protocols. This is prototypically exemplified by neuroblastoma, where MYCN amplification occurs in about 25% of the cases. Intriguingly, MRE11 is highly expressed and predicts bad prognosis in MYCN-amplified neuroblastoma. Due to the lack of direct means to target MYCN, we explored the possibility to trigger intolerable levels of replication stress-dependent DNA damage, by inhibiting MRE11 in MYCN-amplified preclinical models. Indeed, either MRE11 knockdown or its pharmacological inhibitor mirin induce accumulation of replication stress and DNA damage biomarkers in MYCN-amplified cells. The consequent DDR recruits p53 and promotes a p53-dependent cell death, as indicated by p53 loss- and gain-of-function experiments. Encapsulation of mirin in nanoparticles allowed its use on MYCN-amplified neuroblastoma xenografts in vivo, which resulted in a sharp impairment of tumor growth, associated with DDR activation, p53 accumulation, and cell death. Therefore, we propose that MRE11 inhibition might be an effective strategy to treat MYCN-amplified and p53 wild-type neuroblastoma, and suggest that targeting replication stress with appropriate tools should be further exploited to tackle MYCN-driven tumors.
Stage-specific epigenetic regulation of CD4 expression by coordinated enhancer elements during T cell development
Authors: Issuree Priya D. , Day Kenneth , Au Christy , Raviram Ramya , Zappile Paul , Skok Jane A. , Xue Hai-Hui , Myers Richard M. , Littman Dan R. 
Published: August 2018

AbstractThe inheritance of gene expression patterns is dependent on epigenetic regulation, but the establishment and maintenance of epigenetic landscapes during T cell differentiation are incompletely understood. Here we show that two stage-specific Cd4 cis-elements, the previously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway. Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells. Cd4 locus demethylation is important for subsequent Cd4 transcription in activated peripheral T cells wherein these cis-elements become dispensable. By contrast, in developing thymocytes the loss of TET1/3 does not affect Cd4 transcription, highlighting an uncoupled event between transcription and epigenetic modifications. Together our findings reveal an important function for thymic cis-elements in governing gene expression in the periphery via a heritable epigenetic mechanism.
A holistic approach to the age validation of Mullus barbatus L., 1758 in the Southern Adriatic Sea (Central Mediterranean)
Authors: Carbonara Pierluigi , Intini Simona , Kolitari Jerina , Joksimović Aleksandar , Milone Nicoletta , Lembo Giuseppe , Casciaro Loredana , Bitetto Isabella , Zupa Walter , Spedicato Maria Teresa , Sion Letizia 
Published: August 2018

AbstractThe growth of Mullus barbatus has been widely studied using different methods, but no previous study has focused on age validation. The uncertainty in estimating the age of the red mullet by otolith reading is linked to the number of false-growth increments laid down before the annulus. The capture of red mullets in the early life stage allowed us to estimate their size at the metamorphosis from the pelagic to the demersal phase. The comparison between the metamorphosis size and the back-calculated length of the first growth increment clarified the position of the false growth increment on the otolith. Moreover, the analyses of the otolith marginal increments in adult and juvenile specimens allowed us to define the deposition patterns of their annuli. The modal components of the length–frequency distribution analysis (LFDA) were identified in the winter survey (ELEFAN and Bhattacharya methods), and they did not show significant differences from the length back-calculation of the annuli. Moreover, no significant differences were found between the growth curves calculated by otolith reading (back-calculation and direct otolith reading) and the LFDA. The agreement between the length–frequency results and the otolith age estimation either corroborated or indirectly validated the growth pattern estimated in the otoliths of the red mullet, mainly when the direct validation methods (e.g. mark-recapture, captivity, radiochemical) were difficult to implement, like the case of this species. The comparison of the results of the present work to previous Mediterranean studies showed agreement with the slow growth pattern.
Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in raw wastewater as an innovative perspective for investigating population-wide exposure to third-hand smoke
Authors: Lai Foon Yin , Lympousi Katerina , Been Frederic , Benaglia Lisa , Udrisard Robin , Delémont Olivier , Esseiva Pierre , Thomaidis Nikolaos S. , Covaci Adrian , van Nuijs Alexander L. N. 
Published: August 2018

AbstractTobacco smoking is the major cause of many chronic diseases, especially lung cancer. Knowledge about population-wide tobacco use and exposure is essential to characterise its burden on public health and evaluate policy efficacy. Obtaining such knowledge remains challenging with current methods (e.g., surveys, biomonitoring) but can be achievable with wastewater analysis, a promising tool of retrieving epidemiology information. This study examined population-wide exposure to tobacco toxicants and carcinogens through wastewater analysis and explored relationships among these chemicals. Cotinine, trans-3′-hydroxycotinine, anabasine, anatabine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were analysed in samples from Greece, Switzerland and Belgium, where tobacco control policies are different. Measured per-capita mass loads were ranked as: nicotine biomarkers ≫ tobacco markers > carcinogens. Relationships between nicotine biomarkers and tobacco markers implied substantial use of non-tobacco nicotine items besides tobacco products. Geographic profiles of tobacco markers revealed higher levels in Geneva and Athens than Geraardsbergen and Ninove. Environmental third-hand smoke led to NNK detection, with elevated levels observed in Athens where indoor smoking is widespread, posing potential health risks to the population. Our novel outcomes are relevant for public health authorities as they provide indications about external exposure and can thus be used to plan and evaluate tobacco control policies.
The diverse magneto-optical selection rules in bilayer black phosphorus
Authors: Wu Jhao-Ying , Chen Szu-Chao , Do Thi-Nga , Su Wu-Pei , Gumbs Godfrey , Lin Ming-Fa 
Published: August 2018

AbstractThe magneto-optical properties of bilayer phosphorene is investigated by the generalized tight-binding model and the gradient approximation. The vertical inter-Landau-level transitions, being sensitive to the polarization directions, are mainly determined by the spatial symmetries of sub-envelope functions on the distinct sublattices. The anisotropic excitations strongly depend on the electric and magnetic fields. A uniform perpendicular electric field could greatly diversify the selection rule, frequency, intensity, number and form of symmetric absorption peaks. Specifically, the unusual magneto-optical properties appear beyond the critical field as a result of two subgroups of Landau levels with the main and side modes. The rich and unique magnetoabsorption spectra arise from the very close relations among the geometric structures, multiple intralayer and interlayer hopping integrals and composite external fields.
EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion
Authors: Gaber Aljaž , Kim Seung Joong , Kaake Robyn M. , Benčina Mojca , Krogan Nevan , Šali Andrej , Pavšič Miha , Lenarčič Brigita 
Published: August 2018

AbstractCell-surface tumor marker EpCAM plays a key role in proliferation, differentiation and adhesion processes in stem and epithelial cells. It is established as a cell-cell adhesion molecule, forming intercellular interactions through homophilic association. However, the mechanism by which such interactions arise has not yet been fully elucidated. Here, we first show that EpCAM monomers do not associate into oligomers that would resemble an inter-cellular homo-oligomer, capable of mediating cell-cell adhesion, by using SAXS, XL-MS and bead aggregation assays. Second, we also show that EpCAM forms stable dimers on the surface of a cell with pre-formed cell-cell contacts using FLIM-FRET; however, no inter-cellular homo-oligomers were detectable. Thus, our study provides clear evidence that EpCAM indeed does not function as a homophilic cell adhesion molecule and therefore calls for a significant revision of its role in both normal and cancerous tissues. In the light of this, we strongly support the previously suggested name Epithelial Cell Activating Molecule instead of the Epithelial Cell Adhesion Molecule.
Functional diversity of brain networks supports consciousness and verbal intelligence
Authors: Naci Lorina , Haugg Amelie , MacDonald Alex , Anello Mimma , Houldin Evan , Naqshbandi Shakib , Gonzalez-Lara Laura E. , Arango Miguel , Harle Christopher , Cusack Rhodri , Owen Adrian M. 
Published: August 2018

AbstractHow are the myriad stimuli arriving at our senses transformed into conscious thought? To address this question, in a series of studies, we asked whether a common mechanism underlies loss of information processing in unconscious states across different conditions, which could shed light on the brain mechanisms of conscious cognition. With a novel approach, we brought together for the first time, data from the same paradigm—a highly engaging auditory-only narrative—in three independent domains: anesthesia-induced unconsciousness, unconsciousness after brain injury, and individual differences in intellectual abilities during conscious cognition. During external stimulation in the unconscious state, the functional differentiation between the auditory and fronto-parietal systems decreased significantly relatively to the conscious state. Conversely, we found that stronger functional differentiation between these systems in response to external stimulation predicted higher intellectual abilities during conscious cognition, in particular higher verbal acuity scores in independent cognitive testing battery. These convergent findings suggest that the responsivity of sensory and higher-order brain systems to external stimulation, especially through the diversification of their functional responses is an essential feature of conscious cognition and verbal intelligence.
Association of the IP3R to STIM1 provides a reduced intraluminal calcium microenvironment, resulting in enhanced store-operated calcium entry
Authors: Sampieri Alicia , Santoyo Karla , Asanov Alexander , Vaca Luis 
Published: August 2018

AbstractThe involvement of inositol trisphosphate receptor (IP3R) in modulating store-operated calcium entry (SOCE) was established many years ago. Nevertheless, the molecular mechanism responsible for this observation has not been elucidated to this date. In the present study we show that IP3R associates to STIM1 upon depletion of the endoplasmic reticulum (ER) by activation of the inositol trisphosphate signaling cascade via G-protein coupled receptors. IP3R-STIM1 association results in enhanced STIM1 puncta formation and larger Orai-mediated whole-cell currents as well as increased calcium influx. Depleting the ER with a calcium ATPase inhibitor (thapsigargin, TG) does not induce IP3R-STIM1 association, indicating that this association requires an active IP3R. The IP3R-STIM1 association is only observed after IP3R activation, as evidenced by FRET experiments and co-immunoprecipitation assays. ER intraluminal calcium measurements using Mag-Fluo-4 showed enhanced calcium depletion when IP3R is overexpressed. A STIM1-GCaMP fusion protein indicates that STIM1 detects lower calcium concentrations near its EF-hand domain when IP3R is overexpressed when compared with the fluorescence reported by a GCaMP homogenously distributed in the ER lumen (ER-GCaMP). All these data together strongly suggest that activation of inositol trisphosphate signaling cascade induces the formation of the IP3R-STIM1 complex. The activated IP3R provides a reduced intraluminal calcium microenvironment near STIM1, resulting in enhanced activation of Orai currents and SOCE.
Diagnostics of Data-Driven Models: Uncertainty Quantification of PM7 Semi-Empirical Quantum Chemical Method
Authors: Oreluk James , Liu Zhenyuan , Hegde Arun , Li Wenyu , Packard Andrew , Frenklach Michael , Zubarev Dmitry 
Published: August 2018

AbstractWe report an evaluation of a semi-empirical quantum chemical method PM7 from the perspective of uncertainty quantification. Specifically, we apply Bound-to-Bound Data Collaboration, an uncertainty quantification framework, to characterize (a) variability of PM7 model parameter values consistent with the uncertainty in the training data and (b) uncertainty propagation from the training data to the model predictions. Experimental heats of formation of a homologous series of linear alkanes are used as the property of interest. The training data are chemically accurate, i.e., they have very low uncertainty by the standards of computational chemistry. The analysis does not find evidence of PM7 consistency with the entire data set considered as no single set of parameter values is found that captures the experimental uncertainties of all training data. A set of parameter values for PM7 was able to capture the training data within ±1 kcal/mol, but not to the smaller level of uncertainty in the reported data. Nevertheless, PM7 was found to be consistent for subsets of the training data. In such cases, uncertainty propagation from the chemically accurate training data to the predicted values preserves error within bounds of chemical accuracy if predictions are made for the molecules of comparable size. Otherwise, the error grows linearly with the relative size of the molecules.
Effect of the prebiotic fiber inulin on cholesterol metabolism in wildtype mice
Authors: Mistry Rima H. , Gu Fangjie , Schols Henk A. , Verkade Henkjan J. , Tietge Uwe J. F. 
Published: August 2018

AbstractDietary non-digestible carbohydrates are perceived to improve health via gut microbiota-dependent generation of products such as short-chain fatty acids (SCFA). In addition, SCFA are also precursors for lipid and cholesterol synthesis potentially resulting in unwanted effects on lipid metabolism. Inulin is a widely used model prebiotic dietary fiber. Inconsistent reports on the effects of inulin on cholesterol homeostasis have emerged in humans and preclinical models. To clarify this issue, the present study aimed to provide an in-depth characterization of the effects of short-chain (sc)- and long-chain (lc)- inulin on cholesterol synthesis, absorption and elimination in mice. Feeding wildtype C57BL/6J mice diets supplemented with 10% (w/w) of either sc- or lc-inulin for two weeks resulted in approximately 2.5-fold higher fecal SCFA levels (P < 0.01) compared with controls, but had no significant effects on plasma and liver lipids. Subtle shifts in fecal and plasma bile acid species were detected with beta-muricholic acid increasing significantly in plasma of the inulin fed groups (1.7-fold, P < 0.05). However, neither sc-inulin nor lc-inulin affected intestinal cholesterol absorption, mass fecal cholesterol excretion or trans-intestinal cholesterol excretion (TICE). Combined, our data demonstrate that sc- and lc-inulin have no adverse effects on cholesterol metabolism in mice despite increased generation of SCFA.
Jiamusi pulsar observations
Authors: Wang P. F. , Han J. L. , Han L. , Zhang J. H. , Li J. Q. , Wang C. , Han J. , Wang T. , Gao X. Y. 
Published: August 2018

Context. Pulsars scintillate. Dynamic spectra show brightness variation of pulsars in the time and frequency domain. Secondary spectra demonstrate the distribution of fluctuation power in the dynamic spectra.
Aims. Dynamic spectra strongly depend on observational frequencies, but were often observed at frequencies lower than 1.5 GHz. Scintillation observations at higher frequencies help to constrain the turbulence feature of the interstellar medium over a wide frequency range and can detect the scintillations of more distant pulsars.
Methods. Ten pulsars were observed at 2250 MHz (S-band) with the Jiamusi 66 m telescope to study their scintillations. Their dynamic spectra were first obtained, from which the decorrelation bandwidths and timescales of diffractive scintillation were then derived by autocorrelation. Secondary spectra were calculated by forming the Fourier power spectra of the dynamic spectra.
Results. Most of the newly obtained dynamic spectra are at the highest frequency or have the longest time span of any published data for these pulsars. For PSRs B0540 + 23, B2324 + 60, and B2351 + 61, these were the first dynamic spectra ever reported. The frequency dependence of the scintillation parameters indicates that the intervening medium can rarely be ideally turbulent with a Kolmogorov spectrum. The thin-screen model worked well at S-band for the scintillation of PSR B1933 + 16. Parabolic arcs were detected in the secondary spectra of three pulsars, PSRs B0355 + 54, B0540 + 23, and B2154 + 40, all of which were asymmetrically distributed. The inverted arclets of PSR B0355 + 54 were seen to evolve along the main parabola within a continuous observing session of 12 h, from which the angular velocity of the pulsar was estimated. This was consistent with the measurement by very long baseline interferometry.
Recent Progress in σ-Bond Cross-Exchange Reactions to Access Diverse Silacycles
Authors: Zhao Dongbing , Zhao Wen-Tao , Gao Fang 
Published: August 2018

The σ-bond cross-exchange reaction, which involves cleavage and subsequent exchange between different nonpolar σ-bonds, constitutes an attractive protocol for rapid access to organic skeletons with 100% atom economy. Herein, we give a brief summary of recent achievements in this approach for the synthesis of diverse silacycles, highlighting our recent advances in the first intermolecular σ-bond exchange between C–C bonds of cyclopropenones and C–Si bonds of (benzo)silacyclobutanes.1	Introduction2	σ-Bond Exchange-Reaction of Benzocyclobutanones to Silacycles3	σ-Bond Exchange-Reaction of Ethyl Cyclopropylideneacetates to Silacycles4	σ-Bond Exchange-Reaction of Cyclopropenones to Silacycles5	Conclusion
Effects of Illiteracy on the European Cross-Cultural Neuropsychological Test Battery (CNTB)
Authors: Nielsen T Rune 
Published: August 2018

Abstract

Objectives
Test performances of illiterate and literate immigrants were compared to investigate the effects of illiteracy on the European Cross-cultural Neuropsychological Test Battery (CNTB), and associations between test performance and participant characteristics were examined.

Method
Participants were 20 illiterate and 21 literate middle-aged and older Turkish immigrants (50–85 years) matched by age and gender that completed the CNTB as well as a number of demographic and medical questionnaires.

Results
No significant group differences or correlations between education, acculturation or health characteristics and test performances were found on 10 of 16 measures. Illiteracy status and participant characteristics affected measures of mental processing speed, executive function, and visuoconstruction.

Conclusions
The preliminary findings suggest that several of the measures in the CNTB may be valid for assessment of cognitive functioning in people who are illiterate when applied using available normative data. However, these findings need to be replicated in larger samples.