bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splice form variant and amino acid changes in MDR49 confers DDT resistance in transgenic Drosophila
Authors: Seong Keon Mook , Sun Weilin , Clark John M. , Pittendrigh Barry R. 
Published: March 2016

AbstractThe ATP-binding cassette (ABC) transporters represent a superfamily of proteins that have important physiological roles in both prokaryotes and eukaryotes. In insects, ABC transporters have previously been implicated in insecticide resistance. The 91-R strain of Drosophila melanogaster has been intensely selected with DDT over six decades. A recent selective sweeps analysis of 91-R implicated the potential role of MDR49, an ABC transporter, in DDT resistance, however, to date the details of how MDR49 may play a role in resistance have not been elucidated. In this study, we investigated the impact of structural changes and an alternative splicing event in MDR49 on DDT-resistance in 91-R, as compared to the DDT susceptible strain 91-C. We observed three amino acid differences in MDR49 when 91-R was compared with 91-C, and only one isoform (MDR49B) was implicated in DDT resistance. A transgenic Drosophila strain containing the 91-R-MDR49B isoform had a significantly higher LD50 value as compared to the 91-C-MDR49B isoform at the early time points (6 h to 12 h) during DDT exposure. Our data support the hypothesis that the MDR49B isoform, with three amino acid mutations, plays a role in the early aspects of DDT resistance in 91-R.
Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo
Authors: Gao Peng , Zhang Haoqiang , Liu Yun , Fan Bo , Li Xiaokang , Xiao Xin , Lan Pingheng , Li Minghui , Geng Lei , Liu Dong , Yuan Yulin , Lian Qin , Lu Jianxi , Guo Zheng , Wang Zhen 
Published: March 2016

AbstractThe drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable β-tricalcium phosphate (β-TCP) granules for bone regeneration and identify an efficient method to establish β-TCP-based osteo-regenerators. β-TCP granules with diameters of 1 mm and 1–2.5 mm were evaluated in vitro. The β-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1–2.5 mm β-TCP compared with 1-mm granules (P < 0.05). In addition, BMSCs incubated with 1–2.5 mm β-TCP expressed significantly higher levels of the genes for runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 and the osteogenesis-related proteins alkaline phosphatase, collagen type-1 and runt-related transcription factor-2 compared with BMSCs incubated with 1 mm β-TCP (P < 0.05). Fluorochrome labelling, micro-computed tomography and histological staining analyses indicated that the osteo-regenerator with two holes perforating the femur promoted significantly greater bone regeneration compared with the osteo-regenerator with a periosteum incision (P < 0.05). This study provides an alternative to biofunctionalized bioreactors that exhibits improved osteogenesis.
Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study
Authors: Tao Xia , Thijssen Stephan , Kotanko Peter , Ho Chih-Hu , Henrie Michael , Stroup Eric , Handelman Garry 
Published: March 2016

AbstractProtein-bound uraemic toxins (PBUTs) cause various deleterious effects in end-stage kidney disease patients, because their removal by conventional haemodialysis (HD) is severely limited by their low free fraction in plasma. Here we provide an experimental validation of the concept that the HD dialytic removal of PBUTs can be significantly increased by extracorporeal infusion of PBUT binding competitors. The binding properties of indoxyl sulfate (IS), indole-3-acetic acid (IAA) and hippuric acid (HIPA) and their binding competitors, ibuprofen (IBU), furosemide (FUR) and tryptophan (TRP) were studied in uraemic plasma. The effect of binding competitor infusion on fractional removal of PBUT was then quantified in an ex vivo single-pass HD model using uraemic human whole blood. The infusion of a combination of IBU and FUR increased the fractional removal of IS from 6.4 ± 0.1 to 18.3 ± 0.4%. IAA removal rose from 16.8 ± 0.3 to 34.5 ± 0.7%. TRP infusion increased the removal of IS and IAA to 10.5 ± 0.1% and 27.1 ± 0.3%, respectively. Moderate effects were observed on HIPA removal. Pre-dialyzer infusion of PBUT binding competitors into the blood stream can increase the HD removal of PBUTs. This approach can potentially be applied in current HD settings.
PSCA rs2294008 polymorphism contributes to the decreased risk for cervical cancer in a Chinese population
Authors: Wang Shizhi , Wu Shenshen , Zhu Haixia , Ding Bo , Cai Yunlang , Ni Jing , Wu Qiang , Meng Qingtao , Zhang Xin , Zhang Chengcheng , Li Xiaobo , Wang Meilin , Chen Rui , Jin Hua , Zhang Zhengdong 
Published: March 2016

AbstractRecently, three genome-wide association studies have identified the PSCA (prostate stem cell antigen) rs2294008 polymorphism (C > T) associated with susceptibility to gastric cancer, bladder cancer, and duodenal ulcers, highlighting its critical role in disease pathogenesis. Given PSCA is reported to be overexpressed in cervical cancer and the rs2294008 can influence PSCA transcription, we aimed to determine the role of rs2294008 in susceptibility to cervical cancer. The genotyping was performed in the 1126 cases and 1237 controls. Our results showed the rs2294008 TT genotype significantly associated with a reduced risk of cervical cancer (adjusted OR = 0.55, 95% CI = 0.38–0.79; recessive model). Stratified analyses revealed that the association was restricted to the subgroups of age > 49 years, parity ≤ 1, abortion and early-stage cervical cancer. Immunohistochemistry assay showed the individuals carrying the TT genotype having lower PSCA expression than those with CC/CT genotypes. In summary, the PSCA rs2294008 polymorphism may serve as a biomarker of cervical cancer, particularly of early-stage cervical cancer.
UniBic: Sequential row-based biclustering algorithm for analysis of gene expression data
Authors: Wang Zhenjia , Li Guojun , Robinson Robert W. , Huang Xiuzhen 
Published: March 2016

AbstractBiclustering algorithms, which aim to provide an effective and efficient way to analyze gene expression data by finding a group of genes with trend-preserving expression patterns under certain conditions, have been widely developed since Morgan et al. pioneered a work about partitioning a data matrix into submatrices with approximately constant values. However, the identification of general trend-preserving biclusters which are the most meaningful substructures hidden in gene expression data remains a highly challenging problem. We found an elementary method by which biologically meaningful trend-preserving biclusters can be readily identified from noisy and complex large data. The basic idea is to apply the longest common subsequence (LCS) framework to selected pairs of rows in an index matrix derived from an input data matrix to locate a seed for each bicluster to be identified. We tested it on synthetic and real datasets and compared its performance with currently competitive biclustering tools. We found that the new algorithm, named UniBic, outperformed all previous biclustering algorithms in terms of commonly used evaluation scenarios except for BicSPAM on narrow biclusters. The latter was somewhat better at finding narrow biclusters, the task for which it was specifically designed.
Solitonic dynamics and excitations of the nonlinear Schrödinger equation with third-order dispersion in non-Hermitian PT-symmetric potentials
Authors: Chen Yong , Yan Zhenya 
Published: March 2016

AbstractSolitons are of the important significant in many fields of nonlinear science such as nonlinear optics, Bose-Einstein condensates, plamas physics, biology, fluid mechanics and etc. The stable solitons have been captured not only theoretically and experimentally in both linear and nonlinear Schrödinger (NLS) equations in the presence of non-Hermitian potentials since the concept of the parity-time "Equation missing"-symmetry was introduced in 1998. In this paper, we present novel bright solitons of the NLS equation with third-order dispersion in some complex "Equation missing"-symmetric potentials (e.g., physically relevant "Equation missing"-symmetric Scarff-II-like and harmonic-Gaussian potentials). We find stable nonlinear modes even if the respective linear "Equation missing"-symmetric phases are broken. Moreover, we also use the adiabatic changes of the control parameters to excite the initial modes related to exact solitons to reach stable nonlinear modes. The elastic interactions of two solitons are exhibited in the third-order NLS equation with "Equation missing"-symmetric potentials. Our results predict the dynamical phenomena of soliton equations in the presence of third-order dispersion and "Equation missing"-symmetric potentials arising in nonlinear fiber optics and other physically relevant fields.
Precipitation shapes communities of arbuscular mycorrhizal fungi in Tibetan alpine steppe
Authors: Zhang Jing , Wang Fang , Che Rongxiao , Wang Ping , Liu Hanke , Ji Baoming , Cui Xiaoyong 
Published: March 2016

AbstractTibetan Plateau is one of the largest and most unique habitats for organisms including arbuscular mycorrhizal fungi (AMF). However, it remains unclear how AMF communities respond to key environmental changes in this harsh environment. To test if precipitation could be a driving force in shaping AMF community structures at regional scale, we examined AMF communities associated with dominant plant species along a precipitation gradient in Tibetan alpine steppe. Rhizosphere soils were collected from five sites with annual precipitation decreasing from 400 to 50 mm. A total of 31 AMF operational taxonomic units (OTUs) were identified. AMF community composition varied significantly among sites, whereas AMF community composition did not vary among plant species. Path analysis revealed that precipitation directly affected AMF hyphal length density, and indirectly influenced AMF species richness likely through the mediation of plant coverage. Our results suggested that water availability could drive the changes of AMF communities at regional scale. Given the important roles AMF could play in the dynamics of plant communities, exploring the changes of AMF communities along key environmental gradients would help us better predict the ecosystem level responses of the Tibetan vegetation to future climate change.
BRE plays an essential role in preventing replicative and DNA damage-induced premature senescence
Authors: Shi Wenting , Tang Mei Kuen , Yao Yao , Tang Chengcheng , Chui Yiu Loon , Lee Kenneth Ka Ho 
Published: March 2016

AbstractThe BRE gene, alias BRCC45, produces a 44 kDa protein that is normally distributed in both cytoplasm and nucleus. In this study, we used adult fibroblasts isolated from wild-type (WT) and BRE knockout (BRE−/−) mice to investigate the functional role of BRE in DNA repair and cellular senescence. We compared WT with BRE−/− fibroblasts at different cell passages and observed that the mutant fibroblasts entered replicative senescence earlier than the WT fibroblasts. With the use of gamma irradiation to induce DNA damage in fibroblasts, the percentage of SA-β-Gal+ cells was significantly higher in BRE−/− fibroblasts compared with WT cells, suggesting that BRE is also associated with DNA damage-induced premature senescence. We also demonstrated that the gamma irradiation induced γ-H2AX foci, a DNA damage marker, persisted significantly longer in BRE−/− fibroblasts than in WT fibroblasts, confirming that the DNA repair process is impaired in the absence of BRE. In addition, the BRCA1-A complex recruitment and homologous recombination (HR)-dependent DNA repair process upon DNA damage were impaired in BRE−/− fibroblasts. Taken together, our results demonstrate a role for BRE in both replicative senescence and DNA damage-induced premature senescence. This can be attributed to BRE being required for BRCA1-A complex-driven HR DNA repair.
DephosSite: a machine learning approach for discovering phosphotase-specific dephosphorylation sites
Authors: Wang Xiaofeng , Yan Renxiang , Song Jiangning 
Published: March 2016

AbstractProtein dephosphorylation, which is an inverse process of phosphorylation, plays a crucial role in a myriad of cellular processes, including mitotic cycle, proliferation, differentiation and cell growth. Compared with tyrosine kinase substrate and phosphorylation site prediction, there is a paucity of studies focusing on computational methods of predicting protein tyrosine phosphatase substrates and dephosphorylation sites. In this work, we developed two elegant models for predicting the substrate dephosphorylation sites of three specific phosphatases, namely, PTP1B, SHP-1 and SHP-2. The first predictor is called MGPS-DEPHOS, which is modified from the GPS (Group-based Prediction System) algorithm with an interpretable capability. The second predictor is called CKSAAP-DEPHOS, which is built through the combination of support vector machine (SVM) and the composition of k-spaced amino acid pairs (CKSAAP) encoding scheme. Benchmarking experiments using jackknife cross validation and 30 repeats of 5-fold cross validation tests show that MGPS-DEPHOS and CKSAAP-DEPHOS achieved AUC values of 0.921, 0.914 and 0.912, for predicting dephosphorylation sites of the three phosphatases PTP1B, SHP-1 and SHP-2, respectively. Both methods outperformed the previously developed kNN-DEPHOS algorithm. In addition, a web server implementing our algorithms is publicly available at http://genomics.fzu.edu.cn/dephossite/ for the research community.
Omnidirectional optical attractor in structured gap-surface plasmon waveguide
Authors: Sheng Chong , Liu Hui , Zhu Shining , Genov Dentcho A. 
Published: March 2016

AbstractAn optical attractor based on a simple and easy to fabricate structured metal-dielectric-metal (SMDM) waveguide is proposed. The structured waveguide has a variable thickness in the vicinity of an embedded microsphere and allow for adiabatic nano-focusing of gap-surface plasmon polaritons (GSPPs). We show that the proposed system acts as an omnidirectional absorber across a broad spectral range. The geometrical optics approximation is used to provide a description of the ray trajectories in the system and identify the singularity of the deflection angle at the photon sphere. The analytical theory is validated by full-wave numerical simulations demonstrating adiabatic, deep sub-wavelength focusing of GSPPs and high local field enhancement. The proposed structured waveguide is an ideal candidate for the demonstration of reflection free omnidirectional absorption of GSPP in the optical and infrared frequency ranges.
Two phases of aging separated by the Smurf transition as a public path to death
Authors: Dambroise E. , Monnier L. , Ruisheng L. , Aguilaniu H. , Joly J.-S. , Tricoire H. , Rera M. 
Published: March 2016

AbstractAging’s most obvious characteristic is the time dependent increase of an individual’s probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined. To identify the very processes driving aging we have developed in the past years an assay to identify physiologically old individuals in a synchronized population of Drosophila melanogaster. Those individuals show an age-dependent increase of intestinal permeability followed by a high risk of death. Here we show that this physiological marker of aging is conserved in 3 invertebrate species Drosophila mojavensis, Drosophila virilis, Caenorhabditis elegans as well as in 1 vertebrate species Danio rerio. Our findings suggest that intestinal barrier dysfunction may be an important event in the aging process conserved across a broad range of species, thus raising the possibility that it may also be the case in Homo sapiens.
NR2A contributes to genesis and propagation of cortical spreading depression in rats
Authors: Bu Fan , Du Ruoxing , Li Yi , Quinn John P , Wang Minyan 
Published: March 2016

AbstractCortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 μM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile.
Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit
Authors: Kenkel W M , Yee J R , Moore K , Madularu D , Kulkarni P , Gamber K , Nedelman M , Ferris C F 
Published: March 2016

AbstractAnxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were ‘odor naive’ to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology.
Simple fault‐tolerant method to balance load in network‐on‐chip
Authors: Xie Ruilian , Cai Jueping , Xin Xin 
Published: March 2016

A fault‐tolerant odd–even (FTOE) turn model and load‐balancing multi‐router fault‐tolerant (LBMF) routing method that do not use virtual channels for mesh network‐on‐chip (NoC) are presented. Applying FTOE rules and routing packets around faulty regions in advance, LBMF balances the load around the faulty regions, and then the fault‐tolerant paths are shortened. Simulation results show that LBMF's network injection rate can be improved than related works by 25, 40% for 16 × 16 mesh and in the presence of 20 faults.
Direction of information flow in large-scale resting-state networks is frequency-dependent
Authors: Hillebrand Arjan , Tewarie Prejaas , van Dellen Edwin , Yu Meichen , Carbo Ellen W. S. , Douw Linda , Gouw Alida A. , van Straaten Elisabeth C. W. , Stam Cornelis J. 
Published: March 2016

SignificanceA description of the structural and functional connections in the human brain is necessary for the understanding of both normal and abnormal brain functioning. Although it has become clear in recent years that stable patterns of functional connectivity can be observed during the resting state, to date, it remains unclear what the dominant patterns of information flow are in this functional connectome and how these relate to the integration of brain function. Our results are the first to describe the large-scale frequency-specific patterns of information flow in the human brain, showing that different subsystems form a loop through which information “reverberates” or “circulates.” These results could be extended to give insights into how such flow optimizes integrative cognitive processing.
Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X
Authors: Wang Jianle , Syrett Camille M. , Kramer Marianne C. , Basu Arindam , Atchison Michael L. , Anguera Montserrat C. 
Published: March 2016

SignificanceFemales have increased immune responsiveness than males, and they are more likely to develop autoimmune disorders. The mechanism underlying these observations is unclear, and hypotheses suggest an important role for the X chromosome. Here, we discover that the inactive X is predisposed to become partially reactivated in mammalian female lymphocytes, resulting in the overexpression of immunity-related genes. We also demonstrate that lymphocytes from systemic lupus erythematosus patients have different epigenetic characteristics on the inactive X that compromises transcriptional silencing. These findings are the first to our knowledge to link the unusual maintenance of X chromosome Inactivation (the female-specific mechanism for dosage compensation) in lymphocytes to the female bias observed with enhanced immunity and autoimmunity susceptibility.
Combgap contributes to recruitment of Polycomb group proteins in
Drosophila
Authors: Ray Payal , De Sandip , Mitra Apratim , Bezstarosti Karel , Demmers Jeroen A. A. , Pfeifer Karl , Kassis Judith A. 
Published: March 2016

Significance
The ability of organisms to regulate gene expression spatially and temporally is a crucial aspect of development and differentiation. Polycomb group proteins (PcG) are a group of transcriptional repressors that mediate silencing of developmental genes in places where they should not be expressed. Mutations in PcG proteins have been implicated in cancer. We aim to understand mechanisms of PcG-mediated repression, and in this study we report the involvement of Combgap, a DNA-binding protein, in PcG recruitment. Combgap binds to GTGT motifs, which are present within the regulatory regions of PcG target genes. Genome-wide analyses suggest that Combgap may directly recruit Polyhomeotic, a PcG protein. Overall, our data help provide a mechanism for PcG recruitment to target genes.