bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiome profile of the amniotic fluid as a predictive biomarker of perinatal outcome
Authors: Urushiyama Daichi , Suda Wataru , Ohnishi Eriko , Araki Ryota , Kiyoshima Chihiro , Kurakazu Masamitsu , Sanui Ayako , Yotsumoto Fusanori , Murata Masaharu , Nabeshima Kazuki , Yasunaga Shin’ichiro , Saito Shigeru , Nomiyama Makoto , Hattori Masahira , Miyamoto Shingo , Hata Kenichiro 
Published: September 2017

AbstractChorioamnionitis (CAM), an inflammation of the foetal membranes due to infection, is associated with preterm birth and poor perinatal prognosis. The present study aimed to determine whether CAM can be diagnosed prior to delivery based on the bacterial composition of the amniotic fluid (AF). AF samples from 79 patients were classified according to placental inflammation: Stage III (n = 32), CAM; Stage II (n = 27), chorionitis; Stage 0-I (n = 20), sub-chorionitis or no neutrophil infiltration; and normal AF in early pregnancy (n = 18). Absolute quantification and sequencing of 16S rDNA showed that in Stage III, the 16S rDNA copy number was significantly higher and the α-diversity index lower than those in the other groups. In principal coordinate analysis, Stage III formed a separate cluster from Stage 0-I, normal AF, and blank. Forty samples were classified as positive for microbiomic CAM (miCAM) defined by the presence of 11 bacterial species that were found to be significantly associated with CAM and some parameters of perinatal prognosis. The diagnostic accuracy for CAM according to miCAM was: sensitivity, approximately 94%, and specificity, 79–87%. Our findings indicate the possibility of predicting CAM prior to delivery based on the AF microbiome profile.
Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD
Authors: Pierantonelli Irene , Rychlicki Chiara , Agostinelli Laura , Giordano Debora Maria , Gaggini Melania , Fraumene Cristina , Saponaro Chiara , Manghina Valeria , Sartini Loris , Mingarelli Eleonora , Pinto Claudio , Buzzigoli Emma , Trozzi Luciano , Giordano Antonio , Marzioni Marco , Minicis Samuele De , Uzzau Sergio , Cinti Saverio , Gastaldelli Amalia , Svegliati-Baroni Gianluca 
Published: September 2017

AbstractNon-Alcoholic Fatty Liver Disease (NAFLD) represents the most common form of chronic liver injury and can progress to cirrhosis and hepatocellular carcinoma. A “multi-hit” theory, involving high fat diet and signals from the gut-liver axis, has been hypothesized. The role of the NLRP3-inflammasome, which senses dangerous signals, is controversial. Nlrp3−/− and wild-type mice were fed a Western-lifestyle diet with fructose in drinking water (HFHC) or a chow diet. Nlrp3−/−-HFHC showed higher hepatic expression of PPAR γ2 (that regulates lipid uptake and storage) and triglyceride content, histological score of liver injury and greater adipose tissue inflammation. In Nlrp3−/−-HFHC, dysregulation of gut immune response with impaired antimicrobial peptides expression, increased intestinal permeability and the occurrence of a dysbiotic microbiota led to bacterial translocation, associated with higher hepatic expression of TLR4 (an LPS receptor) and TLR9 (a receptor for double-stranded bacterial DNA). After antibiotic treatment, gram-negative species and bacterial translocation were reduced, and adverse effects restored both in liver and adipose tissue. In conclusion, the combination of a Western-lifestyle diet with innate immune dysfunction leads to NAFLD progression, mediated at least in part by dysbiosis and bacterial translocation, thus identifying new specific targets for NAFLD therapy.
Growth and Fabrication of High External Quantum Efficiency AlGaN-Based Deep Ultraviolet Light-Emitting Diode Grown on Pattern Si Substrate
Authors: Tran Binh Tinh , Hirayama Hideki 
Published: September 2017

AbstractGrowing III-V semiconductor materials on Si substrates for opto-electronic applications is challenging because their high lattice mismatch and different thermal expansion coefficients cause the epitaxial layers to have low quality. Here we report the growth of a high-quality AlN template on a micro-circle-patterned Si substrate by using NH3 pulsed-flow multilayer AlN growth and epitaxial lateral overgrowth techniques. Then, we fabricated and characterized a deep-ultraviolet light-emitting diode (UV-LED) device using this AlN/patterned Si. By using standard lithography and inductively coupled plasma etching, the Si substrate was prepared with very high pattern density and was made deep enough to grow a thick AlN template with high crystal quality and very few threading dislocations, allowing for further re-growth of the deep UV-LED device. And by combining a transparent p-AlGaN contact layer, an electron blocking layer and using this high quality AlN template: a deep UV-LED device fabricated and showed a strong single sharp electroluminescence (EL) peak at 325 nm and achieved an external quantum efficiency (EQE) of about 0.03%, for a deep UV-LED grown on Si substrate.
Estimating the intrinsic dimension of datasets by a minimal neighborhood information
Authors: Facco Elena , d’Errico Maria , Rodriguez Alex , Laio Alessandro 
Published: September 2017

AbstractAnalyzing large volumes of high-dimensional data is an issue of fundamental importance in data science, molecular simulations and beyond. Several approaches work on the assumption that the important content of a dataset belongs to a manifold whose Intrinsic Dimension (ID) is much lower than the crude large number of coordinates. Such manifold is generally twisted and curved; in addition points on it will be non-uniformly distributed: two factors that make the identification of the ID and its exploitation really hard. Here we propose a new ID estimator using only the distance of the first and the second nearest neighbor of each point in the sample. This extreme minimality enables us to reduce the effects of curvature, of density variation, and the resulting computational cost. The ID estimator is theoretically exact in uniformly distributed datasets, and provides consistent measures in general. When used in combination with block analysis, it allows discriminating the relevant dimensions as a function of the block size. This allows estimating the ID even when the data lie on a manifold perturbed by a high-dimensional noise, a situation often encountered in real world data sets. We demonstrate the usefulness of the approach on molecular simulations and image analysis.
Production of immunodeficient rabbits by multiplex embryo transfer and multiplex gene targeting
Authors: Song Jun , Yang Dongshan , Ruan Jinxue , Zhang Jifeng , Chen Yuqing Eugene , Xu Jie 
Published: September 2017

AbstractImmunodeficient mice have been used predominantly in biomedical research. Realizing that large animal species may have an enhanced ability to predict clinical outcome relative to mice, we worked to develop immunodeficient rabbits by CRISPR/Cas9. We first demonstrated that multiplex embryo transfer efficiently produced multiple lines of single-gene mutant (SGM) founders. Embryos microinjected with single sgRNA targeting FOXN1, RAG2, IL2RG or PRKDC were pooled for embryo transfer. As few as three recipients were used to produce twenty SGM founders for four genes. We then demonstrated the powerful multiplex targeting capacity of CRISPR/Cas9. First, two genes on the same chromosome were targeted simultaneously, resulting in three RAG1/RAG2 double-gene mutant (DGM) founders. Next we microinjected forty-five embryos each with five sgRNAs targeting FOXN1, RAG1, RAG2, IL2RG and PRKDC, and transferred them to two recipients. Five founders were produced: one SGM, two DGM, one triple-gene mutant and one quadruple-gene mutant. The present work demonstrates that multiplex embryo transfer and multiplex gene targeting can be used to quickly and efficiently generate mutant rabbit founders. Four lines of SGM (e.g. FOXN1, RAG2, IL2RG, and PRKDC) immunodeficient rabbits, as well as multigenic mutant immunodeficient rabbits have been produced. These animals may prove useful for biomedical research.
Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT
Authors: Satoh Tadashi , Song Chihong , Zhu Tong , Toshimori Takayasu , Murata Kazuyoshi , Hayashi Yugo , Kamikubo Hironari , Uchihashi Takayuki , Kato Koichi 
Published: September 2017

AbstractIn the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins. In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags. The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin–chaperone complexes. Here we characterise the dynamic structure of this enzyme. Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration. Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements. These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
Simultaneous increase in strength and ductility by decreasing interface energy between Zn and Al phases in cast Al-Zn-Cu alloy
Authors: Han Seung Zeon , Choi Eun-Ae , Park Hyun Woong , Lim Sung Hwan , Lee Jehyun , Ahn Jee Hyuk , Hwang Nong-Moon , Kim Kwangho 
Published: September 2017

AbstractCast-Al alloys that include a high amount of the second element in their matrix have comparatively high strength but low ductility because of the high volume fraction of strengthening phases or undesirable inclusions. Al–Zn alloys that have more than 30 wt% Zn have a tensile strength below 300 MPa, with elongation under 5% in the as-cast state. However, we found that after substitution of 2% Zn by Cu, the tensile strength of as-cast Al–Zn–Cu alloys was 25% higher and ductility was four times higher than for the corresponding Al–35% Zn alloy. Additionally, for the Al–43% Zn alloy with 2% Cu after 1 h solution treatment at 400 °C and water quenching, the tensile strength unexpectedly reached values close to 600 MPa. For the Al–33% Zn alloy with 2% Cu, the tensile strength was 500 MPa with 8% ductility. The unusual trends of the mechanical properties of Al–Zn alloys with Cu addition observed during processing from casting to the subsequent solution treatment were attributed to the precipitation of Zn in the Al matrix. The interface energy between the Zn particles and the Al matrix decreased when using a solution of Cu in Zn.
Infection with Burkholderia pseudomallei – immune correlates of survival in acute melioidosis
Authors: Dunachie Susanna J. , Jenjaroen Kemajittra , Reynolds Catherine J. , Quigley Kathryn J. , Sergeant Ruhena , Sumonwiriya Manutsanun , Chaichana Panjaporn , Chumseng Suchintana , Ariyaprasert Pitchayanant , Lassaux Patricia , Gourlay Louise , Promwong Charuporn , Teparrukkul Prapit , Limmathurotsakul Direk , Day Nicholas P. J. , Altmann Daniel M. , Boyton Rosemary J. 
Published: September 2017

AbstractMelioidosis, caused byBurkholderia pseudomallei, is a potentially lethal infection with no licensed vaccine. There is little understanding of why some exposed individuals have no symptoms, while others rapidly progress to sepsis and death, or why diabetes confers increased susceptibility. We prospectively recruited a cohort of 183 acute melioidosis patients and 21 control subjects from Northeast Thailand and studied immune parameters in the context of survival status and the presence or absence of diabetes. HLA-B*46 (one of the commonest HLA class I alleles in SE Asia) and HLA-C*01 were associated with an increased risk of death (odds ratio 2.8 and 3.1 respectively). Transcriptomic analysis during acute infection in diabetics indicated the importance of interplay between immune pathways including those involved in antigen presentation, chemotaxis, innate and adaptive immunity and their regulation. Survival was associated with enhanced T cell immunity to nine of fifteen immunodominant antigens analysed including AhpC (BPSL2096), BopE (BPSS1525), PilO (BPSS1599), ATP binding protein (BPSS1385) and an uncharacterised protein (BPSL2520). T cell immunity to GroEL (BPSL2697) was specifically impaired in diabetic individuals. This characterization of immunity associated with survival during acute infection offers insights into correlates of protection and a foundation for design of an effective multivalent vaccine.
A combination of NMDA and AMPA receptor antagonists retards granule cell dispersion and epileptogenesis in a model of acquired epilepsy
Authors: Schidlitzki Alina , Twele Friederike , Klee Rebecca , Waltl Inken , Römermann Kerstin , Bröer Sonja , Meller Sebastian , Gerhauser Ingo , Rankovic Vladan , Li Dandan , Brandt Claudia , Bankstahl Marion , Töllner Kathrin , Löscher Wolfgang 
Published: September 2017

AbstractEpilepsy may arise following acute brain insults, but no treatments exist that prevent epilepsy in patients at risk. Here we examined whether a combination of two glutamate receptor antagonists, NBQX and ifenprodil, acting at different receptor subtypes, exerts antiepileptogenic effects in the intrahippocampal kainate mouse model of epilepsy. These drugs were administered over 5 days following kainate. Spontaneous seizures were recorded by video/EEG at different intervals up to 3 months. Initial trials showed that drug treatment during the latent period led to higher mortality than treatment after onset of epilepsy, and further, that combined therapy with both drugs caused higher mortality at doses that appear safe when used singly. We therefore refined the combined-drug protocol, using lower doses. Two weeks after kainate, significantly less mice of the NBQX/ifenprodil group exhibited electroclinical seizures compared to vehicle controls, but this effect was lost at subsequent weeks. The disease modifying effect of the treatment was associated with a transient prevention of granule cell dispersion and less neuronal degeneration in the dentate hilus. These data substantiate the involvement of altered glutamatergic transmission in the early phase of epileptogenesis. Longer treatment with NBQX and ifenprodil may shed further light on the apparent temporal relationship between dentate gyrus reorganization and development of spontaneous seizures.
Fluoxetine and thioridazine inhibit efflux and attenuate crystalline biofilm formation by Proteus mirabilis
Authors: Nzakizwanayo Jonathan , Scavone Paola , Jamshidi Shirin , Hawthorne Joseph A. , Pelling Harriet , Dedi Cinzia , Salvage Jonathan P. , Hind Charlotte K. , Guppy Fergus M. , Barnes Lara M. , Patel Bhavik A. , Rahman Khondaker M. , Sutton Mark J. , Jones Brian V. 
Published: September 2017

AbstractProteus mirabilis forms extensive crystalline biofilms on indwelling urethral catheters that block urine flow and lead to serious clinical complications. The Bcr/CflA efflux system has previously been identified as important for development of P. mirabilis crystalline biofilms, highlighting the potential for efflux pump inhibitors (EPIs) to control catheter blockage. Here we evaluate the potential for drugs already used in human medicine (fluoxetine and thioridazine) to act as EPIs in P. mirabilis, and control crystalline biofilm formation. Both fluoxetine and thioridazine inhibited efflux in P. mirabilis, and molecular modelling predicted both drugs interact strongly with the biofilm-associated Bcr/CflA efflux system. Both EPIs were also found to significantly reduce the rate of P. mirabilis crystalline biofilm formation on catheters, and increase the time taken for catheters to block. Swimming and swarming motilies in P. mirabilis were also significantly reduced by both EPIs. The impact of these drugs on catheter biofilm formation by other uropathogens (Escherichia coli, Pseudomonas aeruginosa) was also explored, and thioridazine was shown to also inhibit biofilm formation in these species. Therefore, repurposing of existing drugs with EPI activity could be a promising approach to control catheter blockage, or biofilm formation on other medical devices.
Separate neural representations of depression, anxiety and apathy in Parkinson’s disease
Authors: Dan Rotem , Růžička Filip , Bezdicek Ondrej , Růžička Evžen , Roth Jan , Vymazal Josef , Goelman Gadi , Jech Robert 
Published: September 2017

AbstractDepression, anxiety and apathy are distinct neuropsychiatric symptoms that highly overlap in Parkinson’s disease (PD). It remains unknown whether each symptom is uniquely associated with a functional network dysfunction. Here, we examined whether individual differences in each neuropsychiatric symptom predict functional connectivity patterns in PD patients while controlling for all other symptoms and motor function. Resting-state functional connectivity MRI were acquired from 27 PD patients and 29 healthy controls. Widespread reduced functional connectivity was identified in PD patients and explained by either the neuropsychiatric or motor symptoms. Depression in PD predicted increased functional connectivity between the orbitofrontal, hippocampal complex, cingulate, caudate and thalamus. Apathy in PD predicted decreased caudate-thalamus and orbitofrontal-parahippocampal connectivity. Anxiety in PD predicted three distinct types of functional connectivity not described before: (i) increased limbic-orbitofrontal cortex; (ii) decreased limbic-dorsolateral prefrontal cortex and orbitofrontal-dorsolateral prefrontal cortices and (iii) decreased sensorimotor-orbitofrontal cortices. The first two types of functional connectivity suggest less voluntary and more automatic emotion regulation. The last type is argued to be specific to PD and reflect an impaired ability of the orbitofrontal cortex to guide goal-directed motor actions in anxious PD patients.
Up-regulation of claudin-2 expression by aldosterone in colonic epithelial cells of mice fed with NaCl-depleted diets
Authors: Furukawa Chisa , Ishizuka Noriko , Hayashi Hisayoshi , Fujii Naoko , Manabe Aya , Tabuchi Yoshiaki , Matsunaga Toshiyuki , Endo Satoshi , Ikari Akira 
Published: September 2017

AbstractDietary NaCl depletion increases Na+ absorption and K+ secretion in the colon, but the mechanisms are not fully understood. In mice fed with NaCl-depleted diets, the expression of claudin-2 and -7 increased compared to those in control mice. Aldosterone (ALD) concentration was also increased. We examined the regulatory mechanism of claudin expression by ALD using the murine colonic epithelial MCE301 cells. ALD dose-dependently increased claudin-2 expression without affecting the expression of claudin-4, -7, -8, and -15. ALD increased nuclear distribution of mineralocorticoid receptor (MR), which was inhibited by spironolactone, an MR antagonist. The ALD-induced elevation of claudin-2 mRNA and protein expression was inhibited by spironolactone, but not by RU-486, a glucocorticoid receptor antagonist. Luciferase reporter assay showed that ALD interacts with the promoter region between -2,021 and -2,008 of human claudin-2. The binding of MR on the promoter region of claudin-2 was increased by ALD, which was inhibited by spironolactone in chromatin immunoprecipitation assay. Our data suggest that ALD acts on MR and increases paracellular permeability to ions mediated by the elevation of claudin-2 expression in the colon. NaCl depletion may increase ALD secretion from adrenal cortex, resulting in the elevation of paracellular permeability to cations in the colon.
Green light activated hydrogen sensing of nanocrystalline composite ZnO-In2O3 films at room temperature
Authors: Ilin A. S. , Ikim M. I. , Forsh P. A. , Belysheva T. V. , Martyshov M. N. , Kashkarov P. K. , Trakhtenberg L. I. 
Published: September 2017

AbstractThe possibility of reducing the operating temperature of H2 gas sensor based on ZnO-In2O3 down to room temperature under green illumination is shown. It is found that sensitivity of ZnO-In2O3 composite to H2 nonmonotonically depends on the oxides’ content. The optimal ratio between the components is chosen. The new mechanism of nanocrystalline ZnO-In2O3 sensor sensitivity to H2 under illumination by green light is proposed. The mechanism considers the illumination turns the composite into nonequilibrium state and the photoconductivity change in the H2 atmosphere is linked with alteration of nonequilibrium charge carriers recombination rate.
Glutaminase 2 expression is associated with regional heterogeneity of 5-aminolevulinic acid fluorescence in glioblastoma
Authors: Kim Sojin , Kim Ja Eun , Kim Yong Hwy , Hwang Taeyoung , Kim Sung Kwon , Xu Wen Jun , Shin Jong-Yeon , Kim Jong-Il , Choi Hyoungseon , Kim Hee Chan , Cho Hye Rim , Choi Anna , Chowdhury Tamrin , Seo Youngbeom , Dho Yun-Sik , Kim Jin Wook , Kim Dong Gyu , Park Sung-Hye , Kim Hyeonjin , Choi Seung Hong , Park Sunghyouk , Lee Se-Hoon , Park Chul-Kee 
Published: September 2017

AbstractFluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is now a widely-used modality for glioblastoma (GBM) treatment. However, intratumoral heterogeneity of fluorescence intensity may reflect different onco-metabolic programs. Here, we investigated the metabolic mechanism underlying the heterogeneity of 5-ALA fluorescence in GBM. Using an in-house developed fluorescence quantification system for tumor tissues, we collected 3 types of GBM tissues on the basis of their fluorescence intensity, which was characterized as strong, weak, and none. Expression profiling by RNA-sequencing revealed 77 genes with a proportional relationship and 509 genes with an inverse relationship between gene expression and fluorescence intensity. Functional analysis and in vitro experiments confirmed glutaminase 2 (GLS2) as a key gene associated with the fluorescence heterogeneity. Subsequent metabolite profiling discovered that insufficient NADPH due to GLS2 underexpression was responsible for the delayed metabolism of 5-ALA and accumulation of protoporphyrin IX (PpIX) in the high fluorescence area. The expression level of GLS2 and related NADPH production capacity is associated with the regional heterogeneity of 5-ALA fluorescence in GBM.