bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of presynaptic filament assembly by the ensemble of S. cerevisiae Rad51 paralogues with Rad52
Authors: Gaines William A. , Godin Stephen K. , Kabbinavar Faiz F. , Rao Timsi , VanDemark Andrew P. , Sung Patrick , Bernstein Kara A. 
Published: July 2015

AbstractThe conserved budding yeast Rad51 paralogues, including Rad55, Rad57, Csm2 and Psy3 are indispensable for homologous recombination (HR)-mediated chromosome damage repair. Rad55 and Rad57 are associated in a heterodimer, while Csm2 and Psy3 form the Shu complex with Shu1 and Shu2. Here we show that Rad55 bridges an interaction between Csm2 with Rad51 and Rad52 and, using a fully reconstituted system, demonstrate that the Shu complex synergizes with Rad55–Rad57 and Rad52 to promote nucleation of Rad51 on single-stranded DNA pre-occupied by replication protein A (RPA). The csm2–F46A allele is unable to interact with Rad55, ablating the ability of the Shu complex to enhance Rad51 presynaptic filament assembly in vitro and impairing HR in vivo. Our results reveal that Rad55–Rad57, the Shu complex and Rad52 act as a functional ensemble to promote Rad51-filament assembly, which has important implications for understanding the role of the human RAD51 paralogues in Fanconi anaemia and cancer predisposition.
Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome
Authors: Thijssen Peter E. , Ito Yuya , Grillo Giacomo , Wang Jun , Velasco Guillaume , Nitta Hirohisa , Unoki Motoko , Yoshihara Minako , Suyama Mikita , Sun Yu , Lemmers Richard J. L. F. , de Greef Jessica C. , Gennery Andrew , Picco Paolo , Kloeckener-Gruissem Barbara , Güngör Tayfun , Reisli Ismail , Picard Capucine , Kebaili Kamila , Roquelaure Bertrand , Iwai Tsuyako , Kondo Ikuko , Kubota Takeo , van Ostaijen-Ten Dam Monique M. , van Tol Maarten J. D. , Weemaes Corry , Francastel Claire , van der Maarel Silvère M. , Sasaki Hiroyuki 
Published: July 2015

AbstractThe life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight the genetic heterogeneity of ICF syndrome; however, they provide evidence that all genes act in common or converging pathways leading to the ICF phenotype.
Randomized, Multicenter Study of Gefitinib Dose-escalation in Advanced Non-small-cell Lung Cancer Patients Achieved Stable Disease after One-month Gefitinib Treatment
Authors: Xue Cong , Hong Shaodong , Li Ning , Feng Weineng , Jia Jun , Peng Jiewen , Lin Daren , Cao Xiaolong , Wang Siyang , Zhang Weimin , Zhang Hongyu , Dong Wei , Zhang Li 
Published: July 2015

AbstractThere is no consensus on the optimal treatment for patients with advanced non-small-cell lung cancer (NSCLC) and stable disease (SD) after gefitinib therapy. This randomized, open-label, multicenter study aimed to explore whether dose-escalation of gefitinib would improve response and survival in NSCLC patients who achieved SD after one-month of standard gefitinib dosage. Between May 2009 and January 2012, 466 patients were enrolled and 100 eligible patients were randomized (1:1) to receive either a higher dose (500 mg/d; H group) or to continue standard dose (250 mg/d; S group) of gefitinib. Objective response rate (ORR) was similar between the two groups (12.5% vs 12.5%, p = 1.000). There were no significant differences regarding progression-free survival (PFS) and overall survival (OS) between both arms (H group vs S group: median PFS, 5.30 months vs 6.23 months, p = 0.167; median OS, 13.70 months vs 18.87 months, p = 0.156). Therefore, dose-escalation of gefitinib does not confer a response or survival advantage in patients who achieve SD with one month of standard-dose gefitinib treatment.
Key innovation or adaptive change? A test of leaf traits using Triodiinae in Australia
Authors: Toon A. , Crisp M. D. , Gamage H. , Mant J. , Morris D. C. , Schmidt S. , Cook L. G. 
Published: July 2015

AbstractThe evolution of novel traits (“key innovations”) allows some lineages to move into new environments or adapt to changing climates, whereas other lineages may track suitable habitat or go extinct. We test whether and how, trait shifts are linked to environmental change using Triodiinae, C4 grasses that form the dominant understory over about 30% of Australia. Using phylogenetic and relaxed molecular clock estimates, we assess the Australian biogeographic origins of Triodiinae and reconstruct the evolution of stomatal and vascular bundle positioning. Triodiinae diversified from the mid-Miocene, coincident with the aridification of Australia. Subsequent niche shifts have been mostly from the Eremaean biome to the savannah, coincident with the expansion of the latter. Biome shifts are correlated with changes in leaf anatomy and radiations within Triodiinae are largely regional. Symplectrodia and Monodia are nested within Triodia. Rather than enabling biome shifts, convergent changes in leaf anatomy have probably occurred after taxa moved into the savannah biome—they are likely to have been subsequent adaptions rather than key innovations. Our study highlights the importance of testing the timing and origin of traits assumed to be phenotypic innovations that enabled ecological shifts.
Myocardial Iron Loading Assessment by Automatic Left Ventricle Segmentation with Morphological Operations and Geodesic Active Contour on T2* images
Authors: Luo Yun-gang , Ko Jacky KL , Shi Lin , Guan Yuefeng , Li Linong , Qin Jing , Heng Pheng-Ann , Chu Winnie CW , Wang Defeng 
Published: July 2015

AbstractMyocardial iron loading thalassemia patients could be identified using T2* magnetic resonance images (MRI). To quantitatively assess cardiac iron loading, we proposed an effective algorithm to segment aligned free induction decay sequential myocardium images based on morphological operations and geodesic active contour (GAC). Nine patients with thalassemia major were recruited (10 male and 16 female) to undergo a thoracic MRI scan in the short axis view. Free induction decay images were registered for T2* mapping. The GAC were utilized to segment aligned MR images with a robust initialization. Segmented myocardium regions were divided into sectors for a region-based quantification of cardiac iron loading. Our proposed automatic segmentation approach achieve a true positive rate at 84.6% and false positive rate at 53.8%. The area difference between manual and automatic segmentation was 25.5% after 1000 iterations. Results from T2* analysis indicated that regions with intensity lower than 20 ms were suffered from heavy iron loading in thalassemia major patients. The proposed method benefited from abundant edge information of the free induction decay sequential MRI. Experiment results demonstrated that the proposed method is feasible in myocardium segmentation and was clinically applicable to measure myocardium iron loading.
Transmembrane protein 106a activates mouse peritoneal macrophages via the MAPK and NF-κB signaling pathways
Authors: Dai Hui , Xu Dong , Su Jing , Jang Jingyuan , Chen Yingyu 
Published: July 2015

AbstractThe M1 and M2 states of macrophage are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. Molecular mechanism analysis indicated that they gain M1 and M2-related functions after encountering specific ligands in the tissue environment. Here, we first characterized the previously unknown immunobiological functions of mouse Tmem106a. This protein is abundantly expressed on the surface of mouse macrophages. Activation of Tmem106a by stimulation with anti-Tmem106a upregulated the expression of CD80, CD86, CD69 and MHC II on macrophage and induced the release of TNF-α, IL-1β, IL-6, CCL2 and NO, but not IL-10. These effects were largely abrogated by pretreatment with siRNA against Tmem106a. Notably, anti-Tmem106a significantly increased iNOS production and phosphorylation of STAT1 and had no effect on the ARGINASE-1 or p-STAT6 level, indicating that anti-Tmem106a activated macrophages and polarized them into M1-like macrophages. Further analysis found that anti-Tmem106a stimulation increased phosphorylation of ERK-1/2, JNK, p38 MAPK, NF-κB p65 and IKKα/β and promoted nuclear translocation of the cytosolic NF-κB p65 subunit. Collectively, these data suggest that mouse Tmem106a might be a new trigger of macrophage activation and have some influence toward the M1 state through the activation of the MAPKs and NF-κB pathway.
Potentiometric detection of chemical vapors using molecularly imprinted polymers as receptors
Authors: Liang Rongning , Chen Lusi , Qin Wei 
Published: July 2015

AbstractIon-selective electrode (ISE) based potentiometric gas sensors have shown to be promising analytical tools for detection of chemical vapors. However, such sensors are only capable of detecting those vapors which can be converted into ionic species in solution. This paper describes for the first time a polymer membrane ISE based potentiometric sensing system for sensitive and selective determination of neutral vapors in the gas phase. A molecularly imprinted polymer (MIP) is incorporated into the ISE membrane and used as the receptor for selective adsorption of the analyte vapor from the gas phase into the sensing membrane phase. An indicator ion with a structure similar to that of the vapor molecule is employed to indicate the change in the MIP binding sites in the membrane induced by the molecular recognition of the vapor. The toluene vapor is used as a model and benzoic acid is chosen as its indicator. Coupled to an apparatus manifold for preparation of vapor samples, the proposed ISE can be utilized to determine volatile toluene in the gas phase and allows potentiometric detection down to parts per million levels. This work demonstrates the possibility of developing a general sensing principle for detection of neutral vapors using ISEs.
Transactivation of human osteoprotegerin promoter by GATA-3
Authors: Kao Shyan-Yuan , Stankovic Konstantina M. 
Published: July 2015

AbstractOsteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations in OPG are involved in a variety of human diseases. We have shown that cochlear spiral ganglion cells secrete OPG at high levels and lack of OPG causes sensorineural hearing loss in addition to the previously described conductive hearing loss. In order to study the regulation of OPG expression, we conducted a database search on regulatory elements in the promoter region of the OPG gene and identified two potential GATA-3 binding sites. Using luciferase assays and site directed mutagenesis, we demonstrate that these two elements are GATA-3 responsive and support GATA-3 transactivation in human HEK and HeLa cells. The expression of wild type GATA-3 activated OPG mRNA and protein expression, while the expression of a dominant negative mutant of GATA-3 or a GATA-3 shRNA construct reduced OPG mRNA and protein levels. GATA-3 deficient cells generated by expressing a GATA-3 shRNA construct were sensitive to apoptosis induced by etoposide and TNF-α. This apoptotic effect could be partly prevented by the co-treatment with exogenous OPG. Our results suggest new approaches to rescue diseases due to GATA-3 deficiency – such as in hypoparathyroidism, sensorineural deafness and renal (HDR) syndrome – by OPG therapy.
Mammalian cochlea as a physics guided evolution-optimized hearing sensor
Authors: Lorimer Tom , Gomez Florian , Stoop Ruedi 
Published: July 2015

AbstractNonlinear physics plays an essential role in hearing. We demonstrate on a mesoscopic description level that during the evolutionary perfection of the hearing sensor, nonlinear physics led to the unique design of the cochlea observed in mammals and that this design requests as a consequence the perception of pitch. Our insight challenges the view that mostly genetics is responsible for the uniformity of the construction of the mammalian hearing sensor. Our analysis also suggests that scaleable and non-scaleable arrangements of nonlinear sound detectors may be at the origin of the differences between hearing sensors in amniotic lineages.
The Hide-and-Seek of Grain Boundaries from Moiré Pattern Fringe of Two-Dimensional Graphene
Authors: Kim Jung Hwa , Kim Kwanpyo , Lee Zonghoon 
Published: July 2015

AbstractGrain boundaries (GBs) commonly exist in crystalline materials and affect various properties of materials. The facile identification of GBs is one of the significant requirements for systematical study of polycrystalline materials including recently emerging two-dimensional materials. Previous observations of GBs have been performed by various tools including high resolution transmission electron microscopy. However, a method to easily identify GBs, especially in the case of low-angle GBs, has not yet been well established. In this paper, we choose graphene bilayers with a GB as a model system and investigate the effects of interlayer rotations to the identification of GBs. We provide a critical condition between adjacent moiré fringe spacings, which determines the possibility of GB recognition. In addition, for monolayer graphene with a grain boundary, we demonstrate that low-angle GBs can be distinguished easily by inducing moiré patterns deliberately with an artificial reference overlay.
Productivity depends more on the rate than the frequency of N addition in a temperate grassland
Authors: Zhang Yunhai , Feng Jinchao , Isbell Forest , Lü Xiaotao , Han Xingguo 
Published: July 2015

AbstractNitrogen (N) is a key limiting resource for aboveground net primary productivity (ANPP) in diverse terrestrial ecosystems. The relative roles of the rate and frequency (additions yr−1) of N application in stimulating ANPP at both the community- and species-levels are largely unknown. By independently manipulating the rate and frequency of N input, with nine rates (from 0 to 50 g N m−2 year−1) crossed with two frequencies (twice year−1 or monthly) in a temperate steppe of northern China across 2008–2013, we found that N addition increased community ANPP and had positive, negative, or neutral effects for individual species. There were similar ANPP responses at the community- or species-level when a particular annual amount of N was added either twice year−1 or monthly. The community ANPP was less sensitive to soil ammonium at lower frequency of N addition. ANPP responses to N addition were positively correlated with annual precipitation. Our results suggest that, over a five-year period, there will be similar ANPP responses to a given annual N input that occurs either frequently in small amounts, as from N deposition, or that occur infrequently in larger amounts, as from application of N fertilizers.
Analysis of IS6110 insertion sites provide a glimpse into genome evolution of Mycobacterium tuberculosis
Authors: Roychowdhury Tanmoy , Mandal Saurav , Bhattacharya Alok 
Published: July 2015

AbstractInsertion sequence (IS) 6110 is found at multiple sites in the Mycobacterium tuberculosis genome and displays a high degree of polymorphism with respect to copy number and insertion sites. Therefore, IS6110 is considered to be a useful molecular marker for diagnosis and strain typing of M. tuberculosis. Generally IS6110 elements are identified using experimental methods, useful for analysis of a limited number of isolates. Since short read genome sequences generated using next-generation sequencing (NGS) platforms are available for a large number of isolates, a computational pipeline for identification of IS6110 elements from these datasets was developed. This study shows results from analysis of NGS data of 1377 M. tuberculosis isolates. These isolates represent all seven major global lineages of M. tuberculosis. Lineage specific copy number patterns and preferential insertion regions were observed. Intra-lineage differences were further analyzed for identifying spoligotype specific variations. Copy number distribution and preferential locations of IS6110 in different lineages imply independent evolution of IS6110, governed mainly through ancestral insertion, fitness (gene truncation, promoter activity) and recombinational loss of some copies. A phylogenetic tree based on IS6110 insertion data of different isolates was constructed in order to understand genome level variations of different markers across different lineages.
Exfoliated MoS2 Sheets and Reduced Graphene Oxide-An Excellent and Fast Anode for Sodium-ion Battery
Authors: Sahu Tuhin Subhra , Mitra Sagar 
Published: July 2015

AbstractThree dimensional (3D) MoS2 nanoflowers are successfully synthesized by hydrothermal method. Further, a composite of as prepared MoS2 nanoflowers and rGO is constructed by simple ultrasonic exfoliation technique. The crystallography and morphological studies have been carried out by XRD, FE-SEM, TEM, HR-TEM and EDS etc. Here, XRD study revealed, a composite of exfoliated MoS2 with expanded spacing of (002) crystal plane and rGO can be prepared by simple 40 minute of ultrasonic treatment. While, FE-SEM and TEM studies depict, individual MoS2 nanoflowers with an average diameter of 200 nm are uniformly distributed throughout the rGO surface. When tested as sodium-ion batteries anode material by applying two different potential windows, the composite demonstrates a high reversible specific capacity of 575 mAhg−1 at 100 mAg−1 in between 0.01 V–2.6 V and 218 mAhg−1 at 50 mAg−1 when discharged in a potential range of 0.4 V–2.6 V. As per our concern, the results are one of the best obtained as compared to the earlier published one on MoS2 based SIB anode material and more importantly this material shows such an excellent reversible Na-storage capacity and good cycling stability without addition of any expensive additive stabilizer, like fluoroethylene carbonate (FEC), in comparison to those in current literature.
A TLR9 agonist enhances the anti-tumor immunity of peptide and lipopeptide vaccines via different mechanisms
Authors: Song Ying-Chyi , Liu Shih-Jen 
Published: July 2015

AbstractThe toll-like receptor 9 (TLR9) agonists CpG oligodeoxynucleotides (CpG ODNs) have been recognized as promising adjuvants for vaccines against infectious diseases and cancer. However, the role of TLR9 signaling in the regulation of antigen uptake and presentation is not well understood. Therefore, to investigate the effects of TLR9 signaling, this study used synthetic peptides (IDG) and lipopeptides (lipoIDG), which are internalized by dendritic cells (DCs) via endocytosis-dependent and endocytosis-independent pathways, respectively. Our data demonstrated that the internalization of lipoIDG and IDG by bone marrow-derived dendritic cells (BMDCs) was not enhanced in the presence of CpG ODNs; however, CpG ODNs prolonged the co-localization of IDG with CpG ODNs in early endosomes. Surprisingly, CpG ODNs enhanced CD8+ T cell responses and the anti-tumor effects of IDG immunization were stronger than those of lipoIDG immunization. LipoIDG admixed with CpG ODNs induced low levels of CD8+ T cells and partially inhibit tumor growth. Our findings suggest that CpG ODNs increase the retention of antigens in early endosomes, which is important for eliciting anti-tumor immunity. These results will facilitate the application of CpG adjuvants in the design of different vaccines.
Anti-angiogenesis therapy and gap junction inhibition reduce MDA-MB-231 breast cancer cell invasion and metastasis in vitro and in vivo
Authors: Zibara Kazem , Awada Zahraa , Dib Leila , El-Saghir Jamal , Al-Ghadban Sara , Ibrik Aida , El-Zein Nabil , El-Sabban Marwan 
Published: July 2015

AbstractCancer cells secrete VEGF, which plays a key role in their growth, invasion, extravasation and metastasis. Direct cancer cell-endothelial cell interaction, mediated by gap junctions, is of critical importance in the extravasation process. In this study, we evaluated avastin (Av), an anti-VEGF antibody; and oleamide (OL), a gap junction inhibitor, using MDA-MB-231 human breast cancer cells in vitro and a xenograft murine model in vivo. Results showed that Av/OL significantly decreased proliferation, induced cell cycle arrest and decreased migration and invasion of MDA-MB-231 cells in vitro. In addition, Av/OL significantly decreased homo and hetero-cellular communication interaction between MDA-MDA and MDA-endothelial cells, respectively. The expression levels of several factors including VEGF, HIF1α, CXCR4, Cx26, Cx43 and MMP9 were attenuated upon Av/OL treatment in vitro. On the other hand, avastin, but not oleamide, reduced tumor size of NSG mice injected subdermally (s.d.) with MDA-MB-231 cells, which was also associated with increased survival. Furthermore, Av but also OL, separately, significantly increased the survival rate and reduced pulmonary and hepatic metastatic foci, of intravenously (i.v.) injected mice. Finally, OL reduced MMP9 protein expression levels, better than Av and in comparisons to control, in the lungs of MDA-MB-231 i.v. injected NSG mice. In conclusion, while avastin has anti-angiogenic, anti-tumor and anti-metastatic activities, oleamide has anti-metastatic activity, presumably at the extravasation level, providing further evidence for the role of gap junction intercellular communication (GJIC) in cancer cell extravasation.
Identification of the miRNA targetome in hippocampal neurons using RIP-seq
Authors: Malmevik Josephine , Petri Rebecca , Klussendorf Thies , Knauff Pina , Åkerblom Malin , Johansson Jenny , Soneji Shamit , Jakobsson Johan 
Published: July 2015

AbstractMicroRNAs (miRNAs) are key players in the regulation of neuronal processes by targeting a large network of target messenger RNAs (mRNAs). However, the identity and function of mRNAs targeted by miRNAs in specific cells of the brain are largely unknown. Here, we established an adeno-associated viral vector (AAV)-based neuron-specific Argonaute2:GFP-RNA immunoprecipitation followed by high-throughput sequencing to analyse the regulatory role of miRNAs in mouse hippocampal neurons. Using this approach, we identified more than two thousand miRNA targets in hippocampal neurons, regulating essential neuronal features such as cell signalling, transcription and axon guidance. Furthermore, we found that stable inhibition of the highly expressed miR-124 and miR-125 in hippocampal neurons led to significant but distinct changes in the AGO2 binding of target mRNAs, resulting in subsequent upregulation of numerous miRNA target genes. These findings greatly enhance our understanding of the miRNA targetome in hippocampal neurons.