bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic Properties of Möbius Cyclacenes Studied by Thermally-Assisted-Occupation Density Functional Theory
Authors: Chung Jui-Hui , Chai Jeng-Da 
Published: February 2019

AbstractIt has been extremely difficult for traditional theoretical methods to adequately predict the properties of systems possessing radical character (i.e., multi-reference systems), especially for multi-reference systems at the nanoscale. To circumvent this, we employ thermally-assisted-occupation density functional theory (TAO-DFT) to predict the electronic properties of Möbius cyclacenes, with the number of fused benzene rings (n) ranging from 8 to 100. In addition, to investigate the significance of Möbius topology, we also compare these properties with the respective properties of cyclacenes and acenes, containing the same number of fused benzene rings. From our TAO-DFT results, Möbius cyclacenes, cyclacenes, and acenes have singlet ground states for all the cases examined. However, unlike acenes, the electronic properties of Möbius cyclacenes and cyclacenes display clear oscillation patterns when n is small (e.g., n ≤ 10 for Möbius cyclacenes and n ≤ 23 for cyclacenes), and converge to the respective properties of acenes when n greatly exceeds 30. The polyradical character of the ground states of Möbius cyclacenes should increase with the molecular size, intimately correlated with the localization of active orbitals at the edges of molecules.
Prognostic impact of ATM mutations in patients with metastatic colorectal cancer
Authors: Randon Giovanni , Fucà Giovanni , Rossini Daniele , Raimondi Alessandra , Pagani Filippo , Perrone Federica , Tamborini Elena , Busico Adele , Peverelli Giorgia , Morano Federica , Niger Monica , Antista Maria , Corallo Salvatore , Saggio Serena , Borelli Beatrice , Zucchelli Gemma , Milione Massimo , Pruneri Giancarlo , Di Bartolomeo Maria , Falcone Alfredo , de Braud Filippo , Cremolini Chiara , Pietrantonio Filippo 
Published: February 2019

AbstractTumors bearing homologous recombination deficiency are extremely sensitive to DNA double strand breaks induced by several chemotherapeutic agents. ATM gene, encoding a protein involved in DNA damage response, is frequently mutated in colorectal cancer (CRC), but its potential role as predictive and prognostic biomarker has not been fully investigated. We carried out a multicenter effort aimed at defining the prognostic impact of ATM mutational status in metastatic CRC (mCRC) patients. Mutational profiles were obtained by means of next-generation sequencing. Overall, 35 out of 227 samples (15%) carried an ATM mutation. At a median follow-up of 56.6 months, patients with ATM mutated tumors showed a significantly longer median overall survival (OS) versus ATM wild-type ones (64.9 vs 34.8 months; HR, 0.50; 95% CI, 0.29–0.85; P = 0.01). In the multivariable model, ATM mutations confirmed the association with longer OS (HR, 0.57; 95% CI, 0.33–0.98; P = 0.04). The prognostic impact of ATM mutations was independent from TP53 mutational status and primary tumor location. High heterogeneity score for ATM mutations, possibly reflecting the loss of wild-type allele, was associated with excellent prognosis. In conclusion, we showed that ATM mutations are independently associated with longer OS in patients with mCRC.
Forskolin and IBMX Induce Neural Transdifferentiation of MSCs Through Downregulation of the NRSF
Authors: Thompson Ryan , Casali Christina , Chan Christina 
Published: February 2019

AbstractNeural differentiation of mesenchymal stem cells is a controversial phenomenon, as it would require transdifferentiation across the mesoderm-ectoderm barrier. However, several laboratories have observed that MSCs are able to be induced to express neural characteristics. Previously, we demonstrated that the cAMP-elevating agents, forskolin and IBMX, induced neural-like differentiation of MSCs, including expression of neural markers and increased sensitivity to neurotransmitters. However, due to the broad range of effects that forskolin and IBMX can elicit through the intracellular second messenger, cAMP, a better mechanistic understanding is required. Here, we show that neural induction by forskolin and IBMX is dependent on downregulation of expression of the master transcriptional regulator, neuron restrictive silencer factor (NRSF), and its downstream target genes. Since silencing of NRSF is known to initiate neural differentiation, it suggests that forskolin and IBMX result in transdifferentiation of MSCs into a neural lineage.
Regulation of the translation activity of antigen-specific mRNA is responsible for antigen loss and tumor immune escape in a HER2-expressing tumor model
Authors: Han Baek-Sang , Ji Sunhee , Woo Sungwon , Lee Ji Heui , Sin Jeong-Im 
Published: February 2019

AbstractTumor cells tend to behave differently in response to immune selective conditions. Contrary to those in therapeutic antitumor conditions, tumor cells in prophylactic antitumor conditions lose antigen expression for antitumor immune escape. Here, using a CT26/HER2 tumor model, we investigate the underlying mechanism(s). We selected tumor cell variants (CT26/HER2-A1 and -A2) displaying resistance to antitumor protective immunity and loss of HER2 antigen expression. These immune-resistant cells failed to induce Ag-specific IgG and IFN-γ responses while forming tumors at the same rate as CT26/HER2 cells. RT-PCR, qRT-PCR, PCR, Western blot and DNA sequencing analyses demonstrated that HER2 expression was inhibited at the post-transcriptional level in these immune-resistant cells, suggesting that tumor cells may escape antitumor immunity through the post-transcriptional regulation of antigen gene expression. The proteasome and lysosomal protein degradation pathways were not responsible for antigen loss, as determined by an inhibitor assay. Finally, HER2 mRNA was found to be not present in the monosomes and polysomes of CT26/HER2-A2 cells, as opposed to CT26/HER2 cells, suggesting that the translation activity of HER2 mRNAs may be suppressed in these immune-resistant cells. Taken together, our results report a new mechanism by which tumor cells respond to antitumor protective immunity for antitumor immune evasion.
Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in female mice
Authors: Patel Vruti , Bidault Guillaume , Chambers Joseph E. , Carobbio Stefania , Everden Angharad J. T. , Garcés Concepción , Dalton Lucy E. , Gribble Fiona M. , Vidal-Puig Antonio , Marciniak Stefan J. 
Published: February 2019

AbstractPhosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.
Decline in Stroke Mortality Between 1997 and 2012 by Sex: Ecological Study in Brazilians Aged 15 to 49 Years
Authors: da Silva Paiva Laércio , Oliveira Fernando Rocha , de Alcantara Sousa Luiz Vinicius , dos Santos Figueiredo Francisco Winter , de Sá Thiago Hérick , Adami Fernando 
Published: February 2019

AbstractThis study aimed to analyse the time trends of stroke mortality between 1997 and 2012 according to sex in Brazilians aged 15 to 49 years. This ecological study used data obtained from the Mortality Information System, which is available from the National Health System Department of Informatics - DATASUS and maintained by the Brazilian Ministry of Health. Stroke definition included International Classification of Disease version 10 (ICD-10) codes I60, I61, I63, and I64. Crude and age-standardized mortality rates and respective 95% confidence intervals were estimated per 100,000 inhabitants and stratified by age, region, year, and sex. Linear regression models were used to analyse the time trends with a confidence level of 95%. The statistical program used was Stata 11.0. Between 1997 and 2012, there were 124,866 deaths due to stroke in Brazilians aged 15 to 49 years. There was a decreasing linear trend in stroke mortality among men (β = −0.46, p < 0.001, R2 = 0.95) and women (β = −0.40, p < 0.001, R2 = 0.98) during this period. Overall there was no significant difference in stroke mortality trends by sex, except with respect to the age group of 40 to 49 years where there was a difference in the decrease of stroke mortality between men and women (interaction sex * year: β = 0.238, p = 0.012, R² = 0.96). Mortality rates decrease significantly over time in men and women in the age group 15 to 49 years old, but there is only significant difference in the decrease of rates by sex only in the age group from 40 to 49 years old.
The IKK-binding domain of NEMO is an irregular coiled coil with a dynamic binding interface
Authors: Barczewski Adam H. , Ragusa Michael J. , Mierke Dale F. , Pellegrini Maria 
Published: February 2019

AbstractNEMO is an essential component in the activation of the canonical NF-κB pathway and exerts its function by recruiting the IκB kinases (IKK) to the IKK complex. Inhibition of the NEMO/IKKs interaction is an attractive therapeutic paradigm for diseases related to NF-κB mis-regulation, but a difficult endeavor because of the extensive protein-protein interface. Here we report the high-resolution structure of the unbound IKKβ-binding domain of NEMO that will greatly facilitate the design of NEMO/IKK inhibitors. The structures of unbound NEMO show a closed conformation that partially occludes the three binding hot-spots and suggest a facile transition to an open state that can accommodate ligand binding. By fusing coiled-coil adaptors to the IKKβ-binding domain of NEMO, we succeeded in creating a protein with improved solution behavior, IKKβ-binding affinity and crystallization compatibility, which will enable the structural characterization of new NEMO/inhibitor complexes.
Vangl2 interaction plays a role in the proteasomal degradation of Prickle2
Authors: Nagaoka Tadahiro , Furuse Mikio , Ohtsuka Toshihisa , Tsuchida Kunihiro , Kishi Masashi 
Published: February 2019

AbstractThe PET and LIM domain-containing protein, Prickle, plays a key role in planar cell polarity (PCP) in Drosophila. It has been reported that mutations in the PRICKLE2 gene, which encodes one of the human orthologues of Prickle, are associated with human diseases such as epilepsy and autism spectrum disorder. To develop preventive and therapeutic strategies for these intractable diseases, we studied the regulation of Prickle2 protein levels in transfected HEK293T cells. Prickle2 levels were negatively regulated by a physical interaction with another PCP protein, Van Gogh-like 2 (Vangl2). The Vangl2-mediated reduction in Prickle2 levels was, at least in part, relieved by proteasome inhibitors or by functional inhibition of the Cullin-1 E3 ubiquitin ligase. Furthermore, the expression of Vangl2 enhanced the polyubiquitination of Prickle2. This ubiquitination was partially blocked by co-expression of a ubiquitin mutant, which cannot be polymerised through their Lys48 residue to induce target proteins toward proteasomal degradation. Together, these results suggest that Prickle2 is polyubiquitinated by the Vangl2 interaction in a Cullin-1-dependent manner to limit its expression levels. This regulation may play a role in the local and temporal fine-tuning of Prickle protein levels during PCP signal-dependent cellular behaviours.
A novel, nature-based alternative for photobioreactor decontaminations
Authors: Krug Lisa , Erlacher Armin , Berg Gabriele , Cernava Tomislav 
Published: February 2019

AbstractLarge-scale microalgae cultivations are increasingly used for the production of animal feed, nutritional supplements and various high-value bioproducts. Due to the process size and other limitations, contaminations of microalgae fermentations with other photoautotrophic microorganism are frequently observed. In the present study, we explored the applicability of 5-isobutyl-2,3-dimethylpyrazine for the removal of contaminating microalgae from industrial photobioreactors. In order to select a representative microbial population for susceptibility experiments, reactor samples were obtained from a multi-stage cultivation process. Assignments of 18S rRNA gene fragment amplicons indicated that Haematococcus, Chlorella, and Scenedesmus were the three most frequently occurring microalgae genera in the selected reactors. Following the isolation of representative algae cultures, susceptibility tests were conducted with the antimicrobial pyrazine. It was demonstrated that all isolated contaminants are highly susceptible to the bioactive compound. The highest tolerance towards the alkylpyrazine was observed with Scenedesmus vacuolatus; solutions with 1.66% (v/v) of the active compound were required for its deactivation. Further tests with the vaporized pyrazine showed consistent reductions in the viability of treated microalgae. This pilot study provides evidence for the applicability of a novel, nature-based alternative for bioreactor decontaminations.
An achiral ferromagnetic/chiral antiferromagnetic bilayer system leading to controllable size and density of skyrmions
Authors: Morvan F. J. , Luo H. B. , Yang H. X. , Zhang X. , Zhou Y. , Zhao G. P. , Xia W. X. , Liu J. P. 
Published: February 2019

AbstractMagnetic skyrmions are topologically protected domain structures related to the Dzyaloshinskii-Moriya interaction (DMI). To understand how magnetic skyrmions occur under different circumstances, we propose a model for skyrmion formation in a bilayer system of ferromagnetic/antiferromagnetic (FM/AFM) films, in which the bulk DMI is only present in the AFM film. Micromagnetic simulations reveal that skyrmions are formed in this system due to the competition between the DMI and demagnetization energies. A critical interfacial exchange energy (Ai = 6.5 mJ/m2) is determined, above which the competition occurs at its full extent. More skyrmions are formed with increasing external magnetic field till a critical value above which the external field is too large and thus leading to the annihilation of skyrmions. The spacing between two skyrmions can be as small as 45 nm. Our results may give technological implications for future skyrmion applications.
3D Muography for the Search of Hidden Cavities
Authors: Cimmino Luigi , Baccani Guglielmo , Noli Pasquale , Amato Lucio , Ambrosino Fabio , Bonechi Lorenzo , Bongi Massimo , Ciulli Vitaliano , D’Alessandro Raffaello , D’Errico Mariaelena , Gonzi Sandro , Melon Barbara , Minin Gianluca , Saracino Giulio , Scognamiglio Luca , Strolin Paolo , Viliani Lorenzo 
Published: February 2019

AbstractMuography (or muon radiography) is a technique that exploits the penetration capability of muons, elementary particles similar to electrons but with a mass about 200 times larger. High energy muons are naturally produced in the interactions of cosmic rays with the Earth atmosphere. The measurement of their absorption in matter allows the imaging of the inner structure of large bodies. The technological developments in the detection of elementary particles have opened the way to its application in various fields, such as archaeology, studies of geological structures, civil engineering and security issues. We have developed a new approach to the three-dimensional muography of underground structures, capable of directly localising hidden cavities and of reconstructing their shape in space. Our measurements at Mt. Echia, the site of the earliest settlement of the city of Naples in the 8th century BC, have led us to the discovery of a hidden underground cavity, whose existence was not evident with the usual two-dimensional muography graphs. We demonstrate here that our original approach definitely enhances muography discovery potential, especially in case of complex underground systems.
Factors involved in initiation and regulation of complement lectin pathway influence postoperative outcome after pediatric cardiac surgery involving cardiopulmonary bypass
Authors: Michalski Mateusz , Pągowska-Klimek Izabela , Thiel Steffen , Świerzko Anna S. , Hansen Annette G. , Jensenius Jens C. , Cedzyński Maciej 
Published: February 2019

AbstractCongenital heart disease (CHD) often requires surgical intervention, and is sometimes associated with life-threatening post-operative complications. We have investigated some factors of the innate immune system involved in the initiation or regulation of complement lectin pathway activation (MASP-1, MASP-2 MASP-3, MAp19, MAp44, ficolin-3) and related them to complications and prognosis in 190 pediatric patients undergoing CHD repair with the use of cardiopulmonary bypass (CPB). Patients with MAp44 levels ≤1.81 µg/ml more frequently experienced low cardiac output syndrome (LCOS), renal insufficiency, systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MODS). Low MASP-3 (≤5.18 µg/ml) and high MASP-1 (≥11.7 µg/ml) levels were often associated with fatal outcome. Low ficolin-3 concentrations (≤10.1 µg/ml) were more common among patients experiencing SIRS and MODS than in those without complications. However, patients suffering from SIRS and MODS with low ficolin-3 had a much better prognosis (91% survivalvs. 37% among other patients; p = 0.007). A discriminating value of 12.7 µg/ml ficolin-3 yielded 8%vs. 60% mortality (p = 0.001). Our data extend the knowledge concerning involvement of proteins of the lectin pathway in development of post-CPB complications. The potential prognostic value of low preoperative MAp44 and high preoperative ficolin-3 seems promising and warrants independent confirmation.
Symmetry-breaking induced magnetic Fano resonances in densely packed arrays of symmetric nanotrimers
Authors: Wang Ning , Zeisberger Matthias , Huebner Uwe , Giannini Vincenzo , Schmidt Markus A. 
Published: February 2019

AbstractDue to unique properties and great design flexibilities, Fano resonances represent one of the most promising optical features mediated by metallic nanostructures, while the excitation of some Fano modes is impossible due to symmetry reasons. The aim of this work is to show that dense lattice arrangements can have a profound impact on the optical properties of nanostructures and, in particular, can enable the excitation of otherwise dark modes. Here, we demonstrate this concept using the example of rectangular arrays of symmetric trimers packed so densely that the coupling between neighbouring unit cells imposes a symmetry break, enabling the excitation of magnetic Fano resonances. We found that in experiments as well as in simulations, electric and magnetic Fano resonances can be simultaneously formed in cases where the inter-trimer distances are sufficiently small. By analysing the transition from an isolated trimer mode into a regime of strong near-field coupling, we show that by modifying the rectangular unit cell lengths due to the symmetry mismatch between lattice and trimer, two types of Fano resonances can be found, especially magnetic Fano resonances with loop-type magnetic field distributions within the centre of each trimer, which can be either enhanced or suppressed. In addition, the influence of the refractive index environment was measured, showing sensitivity values of approximately 300 nm/RIU. Our work provides fundamental insights into the interaction of the lattice and nanostructure response and paves the way towards the observation of novel optical excitations.
A novel mutation tolerant padlock probe design for multiplexed detection of hypervariable RNA viruses
Authors: Ciftci Sibel , Neumann Felix , Hernández-Neuta Iván , Hakhverdyan Mikhayil , Bálint Ádám , Herthnek David , Madaboosi Narayanan , Nilsson Mats 
Published: February 2019

AbstractThe establishment of a robust detection platform for RNA viruses still remains a challenge in molecular diagnostics due to their high mutation rates. Newcastle disease virus (NDV) is one such RNA avian virus with a hypervariable genome and multiple genotypes. Classical approaches like virus isolation, serology, immunoassays and RT-PCR are cumbersome, and limited in terms of specificity and sensitivity. Padlock probes (PLPs) are known for allowing the detection of multiple nucleic acid targets with high specificity, and in combination with Rolling circle amplification (RCA) have permitted the development of versatile pathogen detection assays. In this work, we aimed to detect hypervariable viruses by developing a novel PLP design strategy capable of tolerating mutations while preserving high specificity by targeting several moderately conserved regions and using degenerate bases. For this, we designed nine padlock probes based on the alignment of 335 sequences covering both Class I and II NDV. Our PLP design showed high coverage and specificity for the detection of eight out of ten reported genotypes of Class II NDV field isolated strains, yielding a detection limit of less than ten copies of viral RNA. Further taking advantage of the multiplex capability of PLPs, we successfully extended the assay for the simultaneous detection of three poultry RNA viruses (NDV, IBV and AIV) and combined it with a paper based microfluidic enrichment read-out for digital quantification. In summary, our novel PLP design addresses the current issue of tolerating mutations of highly emerging virus strains with high sensitivity and specificity.
MicroRNAs from saliva of anopheline mosquitoes mimic human endogenous miRNAs and may contribute to vector-host-pathogen interactions
Authors: Arcà Bruno , Colantoni Alessio , Fiorillo Carmine , Severini Francesco , Benes Vladimir , Di Luca Marco , Calogero Raffaele A. , Lombardo Fabrizio 
Published: February 2019

AbstractDuring blood feeding haematophagous arthropods inject into their hosts a cocktail of salivary proteins whose main role is to counteract host haemostasis, inflammation and immunity. However, animal body fluids are known to also carry miRNAs. To get insights into saliva and salivary gland miRNA repertoires of the African malaria vector Anopheles coluzzii we used small RNA-Seq and identified 214 miRNAs, including tissue-enriched, sex-biased and putative novel anopheline miRNAs. Noteworthy, miRNAs were asymmetrically distributed between saliva and salivary glands, suggesting that selected miRNAs may be preferentially directed toward mosquito saliva. The evolutionary conservation of a subset of saliva miRNAs in Anopheles and Aedes mosquitoes, and in the tick Ixodes ricinus, supports the idea of a non-random occurrence pointing to their possible physiological role in blood feeding by arthropods. Strikingly, eleven of the most abundant An. coluzzi saliva miRNAs mimicked human miRNAs. Prediction analysis and search for experimentally validated targets indicated that miRNAs from An. coluzzii saliva may act on host mRNAs involved in immune and inflammatory responses. Overall, this study raises the intriguing hypothesis that miRNAs injected into vertebrates with vector saliva may contribute to host manipulation with possible implication for vector-host interaction and pathogen transmission.