bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional biomarkers for chronic periodontitis and insights into the roles of Prevotella nigrescens and Fusobacterium nucleatum; a metatranscriptome analysis
Authors: Szafrański Szymon P , Deng Zhi-Luo , Tomasch Jürgen , Jarek Michael , Bhuju Sabin , Meisinger Christa , Kühnisch Jan , Sztajer Helena , Wagner-Döbler Irene 
Published: September 2015

Abstract
Background/Objectives:
Periodontitis is the most prevalent inflammatory disease worldwide and is caused by a dysbiotic subgingival biofilm. Here we used metatranscriptomics to determine the functional shift from health to periodontitis, the response of individual species to dysbiosis and to discover biomarkers.

Methods:
Sixteen individuals were studied, from which six were diagnosed with chronic periodontitis. Illumina sequencing of the total messenger RNA (mRNA) yielded ~42 million reads per sample. A total of 324 human oral taxon phylotypes and 366,055 open reading frames from the HOMD database reference genomes were detected.

Results:
The transcriptionally active community shifted from Bacilli and Actinobacteria in health to Bacteroidia, Deltaproteobacteria, Spirochaetes and Synergistetes in periodontitis. Clusters of orthologous groups (COGs) related to carbohydrate transport and catabolism dominated in health, whereas protein degradation and amino acid catabolism dominated in disease. The LEfSe, random forest and support vector machine methods were applied to the 2,000 most highly expressed genes and discovered the three best functional biomarkers, namely haem binding protein HmuY from Porphyromonas gingivalis, flagellar filament core protein FlaB3 from Treponema denticola, and repeat protein of unknown function from Filifactor alocis. They predicted the diagnosis correctly for 14 from 16 individuals, and when applied to an independent study misclassified one out of six subjects only. Prevotella nigrescens shifted from commensalism to virulence by upregulating the expression of metalloproteases and the haem transporter. Expression of genes for the synthesis of the cytotoxic short-chain fatty acid butyrate was observed by Fusobacterium nucleatum under all conditions. Four additional species contributed to butyrate synthesis in periodontitis and they used an additional pathway.

Conclusion:
Gene biomarkers of periodontitis are highly predictive. The pro-inflammatory role of F. nucelatum is not related to butyrate synthesis.
Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes
Authors: Chi Chongwei , Zhang Qian , Mao Yamin , Kou Deqiang , Qiu Jingdan , Ye Jinzuo , Wang Jiandong , Wang Zhongliang , Du Yang , Tian Jie 
Published: September 2015

AbstractAdvanced medical imaging technology has allowed the use of fluorescence molecular imaging-guided breast cancer surgery (FMI-guided BCS) to specifically label tumour cells and to precisely distinguish tumour margins from normal tissues intra-operatively, a major challenge in the medical field. Here, we developed a surgical navigation system for real-time FMI-guided BCS. Tumours derived from highly metastatic 4T1-luc breast cancer cells, which exhibit high expression of matrix metalloproteinase (MMP) and human epidermal growth factor receptor 2 (HER2), were established in nude mice; these mice were injected with smart MMP-targeting and “always-on” HER2-targeting near-infrared (NIR) fluorescent probes. The fluorescence signal was imaged to assess in vivo binding of the probes to the tumour and metastatic sites. Then, orthotopic and metastatic breast tumours were precisely removed under the guidance of our system. The post-operative survival rate of mice was improved by 50% with the new method. Hematoxylin and eosin staining and immunohistochemical staining for MMP2 and CD11b further confirmed the precision of tumour dissection. Our method facilitated the accurate detection and complete removal of breast cancer tumours and provided a method for defining the molecular classification of breast cancer during surgery, thereby improving prognoses and survival rates.
The effects of inhibitory control training for preschoolers on reasoning ability and neural activity
Authors: Liu Qian , Zhu Xinyi , Ziegler Albert , Shi Jiannong 
Published: September 2015

AbstractInhibitory control (including response inhibition and interference control) develops rapidly during the preschool period and is important for early cognitive development. This study aimed to determine the training and transfer effects on response inhibition in young children. Children in the training group (N = 20; 12 boys, mean age 4.87 ± 0.26 years) played “Fruit Ninja” on a tablet computer for 15 min/day, 4 days/week, for 3 weeks. Children in the active control group (N = 20; 10 boys, mean age 4.88 ± 0.20 years) played a coloring game on a tablet computer for 10 min/day, 1–2 days/week, for 3 weeks. Several cognitive tasks (involving inhibitory control, working memory and fluid intelligence) were used to evaluate the transfer effects and electroencephalography (EEG) was performed during a go/no-go task. Progress on the trained game was significant, while performance on a reasoning task (Raven’s Progressive Matrices) revealed a trend-level improvement from pre- to post-test. EEG indicated that the N2 effect of the go/no-go task was enhanced after training for girls. This study is the first to show that pure response inhibition training can potentially improve reasoning ability. Furthermore, gender differences in the training-induced changes in neural activity were found in preschoolers.
Zinc inhibits the reproductive toxicity of Zearalenone in immortalized murine ovarian granular KK-1 cells
Authors: Li Yijia , He Xiaoyun , Yang Xuan , Huang Kunlun , Luo Yunbo , Zhu Liye , Li Yuzhe , Xu Wentao 
Published: September 2015

AbstractZearalenone (ZEA) mainly injures the reproductive system of mammals. In the present study, we aimed to explore the mechanism by which zinc inhibits ZEA-induced reproductive damage in KK-1 cells for the first time. The results shown that both zinc sulfate and zinc gluconate addition increased the intracellular zinc concentration and influenced the expression of zinc transporters (Slc30a1 and Slc39a1) in a time-dependent manner. Co-incubation of zinc with ZEA significantly reduced the ZEA-induced reactive oxygen species and malondialdehyde elevation by promoting the transcription of Mtf1 and Mt2. Meanwhile, two different zincs inhibited the ZEA-induced loss of mitochondrial membrane potential and elevation of late-stage apoptosis via activating the mitochondrial apoptotic pathway by recovering the mRNA and protein expression of pro-apoptotic genes (Bax, Casp3, Casp9). Zinc also recovered cells from S-phase cell cycle arrest. In addition, both of them promoted the ZEA-induced estrogen production but regulated the expression of steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp17a1) in different way. All these results indicated that zinc could inhibit the reproductive toxicity of ZEA.
Identification and Characterization of a Novel Gentisate 1,2-Dioxygenase Gene from a Halophilic Martelella Strain
Authors: Huang Ling , Hu Haiyang , Tang Hongzhi , Liu Yongdi , Xu Ping , Shi Jie , Lin Kuangfei , Luo Qishi , Cui Changzheng 
Published: September 2015

AbstractHalophilic Martelella strain AD-3, isolated from highly saline petroleum-contaminated soil, can efficiently degrade polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene and anthracene, in 3–5% salinity. Gentisic acid is a key intermediate in the microbial degradation of PAH compounds. However, there is little information on PAH degradation by moderately halophilic bacteria. In this study, a 1,077-bp long gene encoding gentisate 1,2-dioxygenase (GDO) from a halophilic Martelella strain AD-3 was cloned, sequenced and expressed in Escherichia coli. The recombinant enzyme GDO was purified and characterized in detail. By using the 18O isotope experiment and LC-MS analysis, the sources of the two oxygen atoms added onto maleylpyruvate were identified as H2O and O2, respectively. The Km and kcat values for gentisic acid were determined to be 26.64 μM and 161.29 s−1, respectively. In addition, optimal GDO activity was observed at 30 °C, pH 7.0 and at 12% salinity. Site-directed mutagenesis demonstrated the importance of four highly conserved His residues at positions 155, 157, 167 and 169 for enzyme activity. This finding provides new insights into mechanism and variety of gentisate 1,2-dioxygenase for PAH degradation in high saline conditions.
Nanoparticles modulate autophagic effect in a dispersity-dependent manner
Authors: Huang Dengtong , Zhou Hualu , Gao Jinhao 
Published: September 2015

AbstractAutophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse nanomaterials have been reported to induce autophagy. However, the underlying mechanisms and universal rules remain unclear. Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate autophagy via tuning their dispersity. Various well-designed univariate experiments demonstrate that nanomaterials induce autophagy in a dispersity-dependent manner. Aggregated nanoparticles induce significant autophagic effect in comparison with well-dispersed nanoparticles. As the highly stable nanoparticles may block autophagic degradation in autolysosomes, endocytosis and intracellular accumulation of nanoparticles can be responsible for this interesting phenomenon. Our results suggest dispersity-dependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy and offer a new alternative way to modulate autophagy.
A Molecular Toolkit to Visualize Native Protein Assemblies in the Context of Human Disease
Authors: Gilmore Brian L. , Winton Carly E. , Demmert Andrew C. , Tanner Justin R. , Bowman Sam , Karageorge Vasilea , Patel Kaya , Sheng Zhi , Kelly Deborah F. 
Published: September 2015

AbstractWe present a new molecular toolkit to investigate protein assemblies natively formed in the context of human disease. The system employs tunable microchips that can be decorated with switchable adaptor molecules to select for target proteins of interest and analyze them using molecular microscopy. Implementing our new streamlined microchip approach, we could directly visualize BRCA1 gene regulatory complexes from patient-derived cancer cells for the first time.
Active mixing of complex fluids at the microscale
Authors: Ober Thomas J. , Foresti Daniele , Lewis Jennifer A. 
Published: September 2015

Significance
The ability to continuously mix complex fluids at the microscale depends on their flow rate, rheology, and mixing rate. New scaling relationships between mixer dimensions and operating conditions are derived and experimentally verified to create a framework for designing active microfluidic mixers that can efficiently homogenize a wide range of materials. Based on this understanding, active mixing printheads are designed and implemented for multimaterial printing of 3D architectures whose local composition and properties can be programmably tailored.
APTANI: a computational tool to select aptamers through sequence-structure motif analysis of HT-SELEX data
Authors: Caroli J. , Taccioli C. , De La Fuente A. , Serafini P. , Bicciato S. 
Published: September 2015

Abstract
Motivation: Aptamers are synthetic nucleic acid molecules that can bind biological targets in virtue of both their sequence and three-dimensional structure. Aptamers are selected using SELEX, Systematic Evolution of Ligands by EXponential enrichment, a technique that exploits aptamer-target binding affinity. The SELEX procedure, coupled with high-throughput sequencing (HT-SELEX), creates billions of random sequences capable of binding different epitopes on specific targets. Since this technique produces enormous amounts of data, computational analysis represents a critical step to screen and select the most biologically relevant sequences.
Results: Here, we present APTANI, a computational tool to identify target-specific aptamers from HT-SELEX data and secondary structure information. APTANI builds on AptaMotif algorithm, originally implemented to analyze SELEX data; extends the applicability of AptaMotif to HT-SELEX data and introduces new functionalities, as the possibility to identify binding motifs, to cluster aptamer families or to compare output results from different HT-SELEX cycles. Tabular and graphical representations facilitate the downstream biological interpretation of results.
Availability and implementation: APTANI is available at http://aptani.unimore.it.
Contact: silvio.bicciato@unimore.it
Supplementary information: Supplementary data are available at Bioinformatics online.
Novel Associations Between Major Histocompatibility Complex and Pediatric‐onset Inflammatory Bowel Disease
Authors: Kolho Kaija‐Leena , Paakkanen Riitta , Lepistö Anna , Wennerstöm Annika , Meri Seppo , Lokki Marja‐Liisa 
Published: September 2015

ABSTRACTPurpose:Major histocompatibility complex (MHC) genes have been widely studied in adult inflammatory bowel disease (IBD), but data on MHC genes are scarce in pediatric IBD. This study focused on MHC association of genes with pediatric‐onset IBD and its different phenotypes.Methods:Blood samples of 103 patients with pediatric IBD (Crohn disease or ulcerative colitis) were collected at Children's Hospital, University of Helsinki, Finland. HLA‐A, ‐B, ‐DRB1 alleles and complement C4A and C4B gene copy numbers were determined and constructed into haplotypes by a Bayesian algorithm (PHASE). A general population cohort (n = 149) served as a control. HLA‐alleles and C4 deficiency frequencies were compared between patients and controls with χ2‐squared and Fisher exact test with Bonferroni correction (Pcorr).Results:One MHC haplotype HLA‐A*03; HLA‐B*07; 1 C4A gene; 1 C4B gene; HLA‐DRB1*15 was more common in Crohn disease and ulcerative colitis than in controls (7/61, 11.5%, 6/42, 14.3% and 1/149, 0.7%, respectively, odds ratio (OR) = 19.19, 95% CI 2.31–159.57, Pcorr = 0.004 for Crohn disease vs controls and OR = 24.67, 95% CI 2.88–211.36, Pcorr = 0.002 for ulcerative colitis vs controls). Two MHC markers were associated with clinical characteristics. HLA‐DRB1*01 was more common in patients with milder disease course, that is, no need for anti–tumor necrosis factor (TNF)‐α medication (18/32, 56.2% vs 19/71, 26.8% without and with anti–TNF‐α medication, respectively, OR = 0.28, 95% CI 0.12–0.68, Pcorr = 0.032). C4B deficiency (<2 C4B genes) was associated with complicated recovery after surgery (12/16, 75.0% vs 4/16, 25.0%, respectively, OR = 9.00, 95% CI 1.82–44.59, Pcorr = 0.025).Conclusions:One MHC haplotype is strongly linked with pediatric‐onset IBD, whereas the need for immunomodulatory therapy and surgery outcome associates with other distinct MHC gene markers.
Histochemical Study of Heparin‐positive Mast Cells in the Terminal Part of Porcine Ductus Choledochus and Papilla Duodeni Major
Authors: Stefanov I. S. , Vodenicharov A. P. , Tsandev N. S. , Sevrieva D. 
Published: September 2015

SummaryThe study presented in detail the localization and density of mast cells (MCs) in the intramural part of the common bile duct (CBD) and in the major duodenal papilla (MDP) of domestic swine. MCs' density (number/mm2) in different layers of both of the duct and papilla was evaluated after toluidine blue staining. Their number was higher in the lamina propria mucosae than in the tunica muscularis of the studied structures. The localization of berberine‐positive, (heparin containing) MCs and the ratio between them and toluidine blue‐positive MCs with γ‐ma metachromasia was also established. Ratios of heparin‐containing MCs in comparison with all toluidine blue‐positive MCs were found as follows: ductus choledochus – 32% in the subglandular connective tissue of lamina propria mucosae in the intramural part of the duct; m. sphincter ductus choledochus – 31% in the circular and 0.06% in the longitudinal muscle layer; subserosa – 59%; papilla duodeni major – 0.03% in the subepithelial connective tissue and 34% in the subglandular connective tissue of lamina propria mucosae, respectively. The established large difference in heparin‐positive MCs in both the subepithelial and subglandular connective tissues of CBD and MDP, respectively, is an evidence for the existence of mucosal and connective tissue MCs.
A Significance Test for Graph-Constrained Estimation
Authors: Zhao Sen , Shojaie Ali 
Published: September 2015

Summary
Graph-constrained estimation methods encourage similarities among neighboring covariates presented as nodes of a graph, and can result in more accurate estimates, especially in high-dimensional settings. Variable selection approaches can then be utilized to select a subset of variables that are associated with the response. However, existing procedures do not provide measures of uncertainty of estimates. Further, the vast majority of existing approaches assume that available graph accurately captures the association among covariates; violations to this assumption could severely hurt the reliability of the resulting estimates. In this article, we present a new inference framework, called the Grace test, which produces coefficient estimates and corresponding p-values by incorporating the external graph information. We show, both theoretically and via numerical studies, that the proposed method asymptotically controls the type-I error rate regardless of the choice of the graph. We also show that when the underlying graph is informative, the Grace test is asymptotically more powerful than similar tests that ignore the external information. We study the power properties of the proposed test when the graph is not fully informative and develop a more powerful Grace-ridge test for such settings. Our numerical studies show that as long as the graph is reasonably informative, the proposed inference procedures deliver improved statistical power over existing methods that ignore external information.
Using the Whole Cohort in the Analysis of Countermatched Samples
Authors: Rivera C. , Lumley T. 
Published: September 2015

Summary
We present a technique for using calibrated weights to incorporate whole-cohort information in the analysis of a countermatched sample. Following Samuelsen's approach for matched case-control sampling, we derive expressions for the marginal sampling probabilities, so that the data can be treated as an unequally-sampled case-cohort design. Pseudolikelihood estimating equations are used to find the estimates. The sampling weights can be calibrated, allowing all whole-cohort variables to be used in estimation; in contrast, the partial likelihood analysis makes use only of a single discrete surrogate for exposure. Using a survey-sampling approach rather than a martingale approach simplifies the theory; in particular, the sampling weights need not be a predictable process. Our simulation results show that pseudolikelihood estimation gives lower efficiency than partial likelihood estimation, but that the gain from calibration of weights can more than compensate for this loss. If there is a good surrogate for exposure, countermatched sampling still outperforms case-cohort and two-phase case-control sampling even when calibrated weights are used. Findings are illustrated with data from the National Wilms’ Tumour Study and the Welsh nickel refinery workers study.
An orthogonal experimental study of phytolith size of Phragmites communis in northeast China
Authors: Liu Lidan , Jie Dongmei , Liu Hongyan , Gao Zhuo , Gao Guizai , Li Nannan , Guo Jixun , Qiao Zhihe 
Published: September 2015

Based on the widespread distribution and abundant phytoliths produced by Phragmites communis, phytoliths of P. communis in northeast China were investigated to identify the primary influencing factors on phytolith size using an orthogonal experimental method. Temperature and precipitation were found to be the prominent factors influencing the sizes of short‐cell phytoliths including the saddle and the rondel morphotypes, whereas there were no obvious variations in the width‐to‐length ratios of short‐cell phytoliths in response to environmental factors. These results indicate that short‐cell phytoliths are genetically stable, confirming that they can be used for the classification of grasses. Moreover, precipitation was the main factor influencing the sizes of the lanceolate phytoliths and silicified stomata, and their width‐to‐length ratios changed significantly in response to precipitation and habitat differences. These findings reveal that lanceolate and silicified stomata phytoliths are sensitive to environmental changes, indicating their usefulness for palaeoenvironment reconstruction. Moreover, variations in their width‐to‐length ratios and their sizes may provide some information for plant classification, even at species level. Finally, the results of a principal component analysis of the sizes of P. communis phytoliths further verify the reliability of the orthogonal experiment results, in that temperature and precipitation were the prominent factors influencing the size of all P. communis phytoliths except for the length of saddle and width of the saddle morphotypes. This research into the primary environmental significance of the sizes of P. communis phytoliths may contribute to improving the precision of plant classification and the model for quantitative reconstruction of the palaeoenvironment to aid in reconstructions of palaeovegetation and palaeoclimate.
The chronostratigraphy of the latest Middle Pleistocene aeolian and alluvial activity on the Island of Hvar, eastern Adriatic, Croatia
Authors: Wacha Lara , Vlahović Igor , Tsukamoto Sumiko , Kovačić Marijan , Hasan Ozren , Pavelić Davor 
Published: September 2015

Pleistocene aeolian sands and alluvial deposits can frequently be traced along the Mediterranean coast. Such deposits also exist along the eastern Adriatic coast and the nearby islands. Four stratigraphical sections of these deposits were studied on the Island of Hvar with the purpose of establishing a chronological framework of the aeolian–alluvial depositional system, using luminescence dating and magnetic susceptibility stratigraphy. Luminescence dating was applied on coarse‐grained feldspar and quartz grains separated from the sands. Both quartz optically stimulated luminescence (OSL) and feldspar post‐IR infrared stimulated luminescence (pIRIR) age estimates are in good agreement, with values ranging between 167±24 to 120±12 ka (OSL) and 179±18 to 131±18 ka (pIRIR measured at 290 °C) after a fading correction for the pIRIR signal. The results can be clearly correlated to around the end of oxygen isotope stage (OIS) 6 and the beginning of OSI 5, indicating that the aeolian accumulation of sands was a result of the Penultimate Glacial and climate fluctuations at the beginning of the Last Interglacial. Variations in magnetic susceptibility (MS) data can be interpreted alongside these dating results; several stronger peaks detected at the very end of the Penultimate Glacial and the initial stage of the Last Interglacial cycle most probably indicates more intensive pedogenesis resulting from a more favourable climate, probably because of climate changes. Breccias related to major bounding surfaces in association with evidence of soil formation and bioturbation could be the result of more favourable climate conditions and changes during the transition from OIS 6 to OIS 5 (Penultimate Glacial–Last Interglacial). These results are in agreement with similar data from the wider Mediterranean area.