bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Alcohol Brand Consumption between Underage Youth and Adults—United States, 2012
Authors: Siegel Michael , Chen Kelsey , DeJong William , Naimi Timothy S. , Ostroff Joshua , Ross Craig S. , Jernigan David H.
Published: February 2014

Background

The alcohol brand preferences of US underage drinkers have recently been identified, but it is not known whether youth are simply mimicking adult brand choices or whether other factors are impacting their preferences. This study is the first to compare the alcohol brand preferences of underage drinkers and adults.

Methods

The authors conducted a cross-sectional assessment of youth and adult alcohol brand preferences. A 2012 Internet-based survey of a nationally representative sample of 1032 underage drinkers, ages 13–20, was used to determine the prevalence of past-30-day consumption for each of 898 alcohol brands, and each brand's youth market share, based on the total number of standard drinks consumed. Data on the brand-specific prevalence of past-30-day or past-7-day consumption among older youth (ages 18–20), adults (ages 21+), and young adults (ages 21–34) was obtained from Gfk MRI's Survey of the Adult Consumer for the years 2010–2012. Overall market shares for each brand, also measured by the total number of standard drinks consumed, were estimated from national data compiled by Impact Databank for the year 2010.

Results

Although most alcohol brands popular among underage drinkers were also popular among adult drinkers, there were several brands that appeared to be disproportionately consumed by youth.

Conclusions

This article provides preliminary evidence that youth do not merely mimic the alcohol brand choices of adults. Further research using data derived from fully comparable data sources is necessary to confirm this finding.
Comparing DNA integration site clusters with scan statistics
Authors: Berry Charles C. , Ocwieja Karen E. , Malani Nirav , Bushman Frederic D.
Published: February 2014

Motivation: Gene therapy with retroviral vectors can induce adverse effects when those vectors integrate in sensitive genomic regions. Retroviral vectors are preferred that target sensitive regions less frequently, motivating the search for localized clusters of integration sites and comparison of the clusters formed by integration of different vectors. Scan statistics allow the discovery of spatial differences in clustering and calculation of false discovery rates providing statistical methods for comparing retroviral vectors.

Results: A scan statistic for comparing two vectors using multiple window widths is proposed with software to detect clustering differentials and compute false discovery rates. Application to several sets of experimentally determined HIV integration sites demonstrates the software. Simulated datasets of various sizes and signal strengths are used to determine the power to discover clusters and evaluate a convenient lower bound. This provides a toolkit for planning evaluations of new gene therapy vectors.

Availability and implementation: The geneRxCluster R package containing a simple tutorial and usage hints is available from http://www.bioconductor.org.

Contact: ccberry@ucsd.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
StochHMM: a flexible hidden Markov model tool and C++ library
Authors: Lott Paul C. , Korf Ian
Published: February 2014

Summary: Hidden Markov models (HMMs) are probabilistic models that are well-suited to solve many different classification problems in computation biology. StochHMM provides a command-line program and C++ library that can implement a traditional HMM from a simple text file. StochHMM provides researchers the flexibility to create higher-order emissions, integrate additional data sources and/or user-defined functions into multiple points within the HMM framework. Additional features include user-defined alphabets, ability to handle ambiguous characters in an emission-dependent manner, user-defined weighting of state paths and ability to tie transition probabilities to sequence.

Availability and implementation: StochHMM is implemented in C++ and is available under the MIT License. Software, source code, documentation and examples can be found at http://github.com/KorfLab/StochHMM.

Contact:  ifkorf@ucdavis.edu
Integrative gene set analysis of multi-platform data with sample heterogeneity
Authors: Hu Jun , Tzeng Jung-Ying
Published: February 2014

Motivation: Gene set analysis is a popular method for large-scale genomic studies. Because genes that have common biological features are analyzed jointly, gene set analysis often achieves better power and generates more biologically informative results. With the advancement of technologies, genomic studies with multi-platform data have become increasingly common. Several strategies have been proposed that integrate genomic data from multiple platforms to perform gene set analysis. To evaluate the performances of existing integrative gene set methods under various scenarios, we conduct a comparative simulation analysis based on The Cancer Genome Atlas breast cancer dataset.

Results: We find that existing methods for gene set analysis are less effective when sample heterogeneity exists. To address this issue, we develop three methods for multi-platform genomic data with heterogeneity: two non-parametric methods, multi-platform Mann–Whitney statistics and multi-platform outlier robust T-statistics, and a parametric method, multi-platform likelihood ratio statistics. Using simulations, we show that the proposed multi-platform Mann–Whitney statistics method has higher power for heterogeneous samples and comparable performance for homogeneous samples when compared with the existing methods. Our real data applications to two datasets of The Cancer Genome Atlas also suggest that the proposed methods are able to identify novel pathways that are missed by other strategies.

Availability and implementation:  http://www4.stat.ncsu.edu/∼jytzeng/Software/Multiplatform_gene_set_analysis/

Contact:  john.hu@omicsoft.com, jhu7@ncsu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Event trigger identification for biomedical events extraction using domain knowledge
Authors: Zhou Deyu , Zhong Dayou , He Yulan
Published: February 2014

Motivation: In molecular biology, molecular events describe observable alterations of biomolecules, such as binding of proteins or RNA production. These events might be responsible for drug reactions or development of certain diseases. As such, biomedical event extraction, the process of automatically detecting description of molecular interactions in research articles, attracted substantial research interest recently. Event trigger identification, detecting the words describing the event types, is a crucial and prerequisite step in the pipeline process of biomedical event extraction. Taking the event types as classes, event trigger identification can be viewed as a classification task. For each word in a sentence, a trained classifier predicts whether the word corresponds to an event type and which event type based on the context features. Therefore, a well-designed feature set with a good level of discrimination and generalization is crucial for the performance of event trigger identification.

Results: In this article, we propose a novel framework for event trigger identification. In particular, we learn biomedical domain knowledge from a large text corpus built from Medline and embed it into word features using neural language modeling. The embedded features are then combined with the syntactic and semantic context features using the multiple kernel learning method. The combined feature set is used for training the event trigger classifier. Experimental results on the golden standard corpus show that >2.5% improvement on F-score is achieved by the proposed framework when compared with the state-of-the-art approach, demonstrating the effectiveness of the proposed framework.

Availability and implementation: The source code for the proposed framework is freely available and can be downloaded at http://cse.seu.edu.cn/people/zhoudeyu/ETI_Sourcecode.zip.

Contact:  d.zhou@seu.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
The TIM-3 pathway ameliorates Theiler’s murine encephalomyelitis virus-induced demyelinating disease
Authors: Kaneyama Tomoki , Tomiki Hiroki , Tsugane Sayaka , Inaba Yuji , Ichikawa Motoki , Akiba Hisaya , Yagita Hideo , Kim Byung S. , Koh Chang-Sung
Published: February 2014

Infection by Theiler’s murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis. T-cell immunoglobulin and mucin domain-3 (TIM-3) has been demonstrated to play a crucial role in the maintenance of peripheral tolerance. In this study, we examined the regulatory role of the TIM-3 pathway in the development of TMEV-induced demyelinating disease (TMEV-IDD). The expression of TIM-3 was increased at both protein and mRNA levels in the spinal cords of mice with TMEV-IDD compared with naive controls. In addition, by utilizing a blocking mAb, we demonstrate that TIM-3 negatively regulates TMEV-specific ex vivo production of IFN-γ and IL-10 by CD4+ T cells and IFN-γ by CD8+ T cells from the CNS of mice with TMEV-IDD at 36 days post-infection (dpi). In vivo blockade of TIM-3 by using the anti-TIM-3 mAb resulted in significant exacerbation of the development of TMEV-IDD both clinically and histologically. The number of infiltrating mononuclear cells in the CNS was also increased in mice administered with anti-TIM-3 mAb both at the induction phase (10 dpi) and at the effector phase (36 dpi). Flow cytometric analysis of intracellular cytokines revealed that the number of CD4+ T cells producing TNF, IL-4, IL-10 and IL-17 was significantly increased at the effector phase in the CNS of anti-TIM-3 mAb-treated mice. These results suggest that the TIM-3 pathway plays a critical role in the regulation of TMEV-IDD.
Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation
Authors: Aik WeiShen , Scotti John S. , Choi Hwanho , Gong Lingzhi , Demetriades Marina , Schofield Christopher J. , McDonough Michael A.
Published: February 2014

ALKBH5 is a 2-oxoglutarate (2OG) and ferrous iron-dependent nucleic acid oxygenase (NAOX) that catalyzes the demethylation of N6-methyladenine in RNA. ALKBH5 is upregulated under hypoxia and plays a role in spermatogenesis. We describe a crystal structure of human ALKBH5 (residues 66–292) to 2.0 Å resolution. ALKBH566–292 has a double-stranded β-helix core fold as observed in other 2OG and iron-dependent oxygenase family members. The active site metal is octahedrally coordinated by an HXD…H motif (comprising residues His204, Asp206 and His266) and three water molecules. ALKBH5 shares a nucleotide recognition lid and conserved active site residues with other NAOXs. A large loop (βIV–V) in ALKBH5 occupies a similar region as the L1 loop of the fat mass and obesity-associated protein that is proposed to confer single-stranded RNA selectivity. Unexpectedly, a small molecule inhibitor, IOX3, was observed covalently attached to the side chain of Cys200 located outside of the active site. Modelling substrate into the active site based on other NAOX–nucleic acid complexes reveals conserved residues important for recognition and demethylation mechanisms. The structural insights will aid in the development of inhibitors selective for NAOXs, for use as functional probes and for therapeutic benefit.
Coordinated repressive chromatin-remodeling of Oct4 and Nanog genes in RA-induced differentiation of embryonic stem cells involves RIP140
Authors: Wu Cheng-Ying , Feng Xudong , Wei Li-Na
Published: February 2014

Maintaining pluripotency and indefinite self-renewal of embryonic stem cells requires a tight control of the expression of several key stemness factors, particularly Nanog and Oct4 transcription factors. The mammalian SWItch/Sucrose NonFermentable (SWI/SNF) complex contains Brg1 or Brm as its core subunit, along with Brg1-associated factors. Our previous studies have addressed chromatin-remodeling of the Oct4 gene locus in retinoic acid (RA)-treated embryonal carcinoma cell line P19, which involves receptor-interacting protein 140 (RIP140) for heterochromatinization on the proximal promoter region of this gene locus. However, the mechanism of RIP140 action in RA-triggered repressive chromatin-remodeling is unclear. The current study examines RA repression of the Nanog gene and compares the results with RA repression of the Oct4 gene on the chromatin level. The results show a loose nucleosome array on the Nanog gene promoter in undifferentiated embryonic stem cells. On RA treatment, the Nanog gene locus remodels specifically in the CR1 region of its proximal promoter, with the insertion of a nucleosome and compaction of this region. Further, RA induces coordinated chromatin-remodeling of both Nanog and Oct4 gene loci, which requires RA receptor-α, RIP140 and Brm. Finally, in these RA-triggered repressive chromatin-remodeling processes, lysine acetylation of RIP140 is critical for its recruiting Brm.
Thermotunica guangxiensis gen. nov., sp. nov., isolated from mushroom residue compost
Authors: Wu Hao , Lian Yunpeng , Liu Bin , Ren Yanling , Qin Peisheng , Huang Fuchang
Published: February 2014

A novel thermophilic actinomycete, designated AG2-7T, was isolated from mushroom residue compost in Guangxi University, Nanning, China. The strain grew optimally at 45–60 °C, at pH 7.0 and with 0–3.0 % (w/v) NaCl. Vegetative mycelia were branched and whitish to pale yellow without fragmentation. Aerial mycelium was abundant, whitish and differentiated into long chains of spores, with a membranous structure or tunica partially covering the surface of aerial hyphae. The non-motile spores were oval in shape with a ridged surface. Strain AG-27T contained meso-diaminopimelic acid as the diagnostic diamino acid, and the whole-cell sugars were galactose and ribose. Major fatty acids were iso-C16 : 0 (27.51 %), iso-C17 : 0 (10.47 %) and anteiso-C17 : 0 (12.01 %). MK-9(H4) was the predominant menaquinone. The polar phospholipids were diphosphatidylglycerol, ninhydrin-positive glycophospholipid, phosphatidylinositol, phosphatidylinositol mannoside, phosphatidylethanolamine, phosphatidylmethylethanolamine, an unknown phospholipid and unknown glucosamine-containing phospholipids. The G+C content of the genomic DNA was 63.6 mol%. 16S rRNA gene sequence analysis showed that the organism belonged to the family

Pseudonocardiaceae

, suborder

Pseudonocardineae

and showed more than 5 % divergence from other members of the family. Based on the phenotypic and phylogenetic data, strain AG2-7T represents a novel species of a new genus in the family

Pseudonocardiaceae

, for which the name Thermotunica guangxiensis gen. nov., sp. nov. is proposed. The type strain of the type species is AG2-7T ( = ATCC BAA-2499T = CGMCC 4.7099T).
Bacillus solimangrovi sp. nov., isolated from mangrove soil
Authors: Lee Geun-Hye , Rhee Moon-Soo , Chang Dong-Ho , Kwon Kae Kyoung , Bae Kyung Sook , Yang Seong-Hyun , Kim Byoung-Chan
Published: February 2014

Two novel bacterial strains, GH2-4T and GH2-5, were isolated from mangrove soil near the seashore of Weno island in Chuuk state, Micronesia, and were characterized by a polyphasic approach. The two strains were strictly aerobic, Gram-staining-positive, motile, endospore-forming rods that were catalase- and oxidase-positive. Colonies were circular, convex, stringy and transparent yellowish (GH2-4T) or opaque whitish (GH2-5). The 16S rRNA gene sequences of the two isolates were identical. The most closely related strains in terms of 16S rRNA gene sequence similarity were

Bacillus kochii

WCC 4582T,

B. horneckiae

DSM 23495T,

B. azotoformans

LMG 9581T,

B. cohnii

DSM 6307T and

B. halmapalus

DSM 8723T (95.6, 95.4, 95.4, 95.2 and 95.2 % similarity, respectively). The partial groEL sequence of strain GH2-4T was identical to that of strain GH2-5 and showed <85 % similarity to those of the most closely related strains. The isolates grew at pH 5–12 (optimal growth at pH 9), at 10–40 °C (optimum 30–35 °C) and at 0–9 % (w/v) NaCl (optimum 1–3 % NaCl). The cell-wall peptidoglycan of strains GH2-4T and GH2-5 contained meso-diaminopimelic acid and cell-wall hydrolysates contained ribose as a major sugar. The DNA G+C content was 36 mol%, and DNA–DNA relatedness between the isolates and five related reference strains was 20–24 %. Strain GH2-4T exhibited 81 % DNA–DNA relatedness with strain GH2-5. The major cellular fatty acids of both strains were iso-C15 : 0, iso-C16 : 0, iso-C14 : 0 and anteiso-C15 : 0 and the predominant menaquinone was MK-7. On the basis of the evidence from this polyphasic study, strains GH2-4T and GH2-5 ( = KCTC 33143 = JCM 18995 = DSM 27084) represent a novel species of the genus

Bacillus

, for which the name Bacillus solimangrovi sp. nov. is proposed; the type strain is GH2-4T ( = KCTC 33142T = JCM 18994T = DSM 27083T).
Flavivirus RNA methylation
Authors: Dong Hongping , Fink Katja , Züst Roland , Lim Siew Pheng , Qin Cheng-Feng , Shi Pei-Yong
Published: February 2014

The 5′ end of eukaryotic mRNA contains the type-1 (m7GpppNm) or type-2 (m7GpppNmNm) cap structure. Many viruses have evolved various mechanisms to develop their own capping enzymes (e.g. flavivirus and coronavirus) or to ‘steal’ caps from host mRNAs (e.g. influenza virus). Other viruses have developed ‘cap-mimicking’ mechanisms by attaching a peptide to the 5′ end of viral RNA (e.g. picornavirus and calicivirus) or by having a complex 5′ RNA structure (internal ribosome entry site) for translation initiation (e.g. picornavirus, pestivirus and hepacivirus). Here we review the diverse viral RNA capping mechanisms. Using flavivirus as a model, we summarize how a single methyltransferase catalyses two distinct N-7 and 2′-O methylations of viral RNA cap in a sequential manner. For antiviral development, a structural feature unique to the flavivirus methyltransferase was successfully used to design selective inhibitors that block viral methyltransferase without affecting host methyltransferases. Functionally, capping is essential for prevention of triphosphate-triggered innate immune activation; N-7 methylation is critical for enhancement of viral translation; and 2′-O methylation is important for subversion of innate immune response during viral infection. Flaviviruses defective in 2′-O methyltransferase are replicative, but their viral RNAs lack 2′-O methylation and are recognized and eliminated by the host immune response. Such mutant viruses could be rationally designed as live attenuated vaccines. This concept has recently been proved with Japanese encephalitis virus and dengue virus. The findings obtained with flavivirus should be applicable to other RNA viruses.
FALDO: A semantic standard for describing the location of nucleotide and protein feature annotation
Authors: Bolleman Jerven , Mungall Christopher J. , Strozzi Francesco , Baran Joachim , Dumontier Michel , Bonnal Raoul J. P. , Buels Robert , Hoehndorf Robert , Fujisawa Takatomo , Katayama Toshi-aki , Cock Peter J. A.
Published: February 2014

BackgroundNucleotide and protein sequence feature annotations are essential to understand biology on the genomic, transcriptomic, and proteomic level. Using Semantic Web technologies to query biological annotations, there was no standard that described this potentially complex location information as subject-predicate-object triples.

DescriptionWe have developed an ontology, the Feature Annotation Location Description Ontology (FALDO), to describe the positions of annotated features on linear and circular sequences. FALDO can be used to describe nucleotide features in sequence records, protein annotations, and glycan binding sites, among other features in coordinate systems of the aforementioned “omics” areas. Using the same data format to represent sequence positions that are independent of file formats allows us to integrate sequence data from multiple sources and data types. The genome browser JBrowse is used to demonstrate accessing multiple SPARQL endpoints to display genomic feature annotations, as well as protein annotations from UniProt mapped to genomic locations.

ConclusionsOur ontology allows users to uniformly describe – and potentially merge – sequence annotations from multiple sources. Data sources using FALDO can prospectively be retrieved using federalised SPARQL queries against public SPARQL endpoints and/or local private triple stores.
Predicting growth conditions from internal metabolic fluxes in anin-Silicomodel ofE. Coli
Authors: Sridhara Viswanadham , Meyer Austin G. , Rai Piyush , Barrick Jeffrey E. , Ravikumar Pradeep , Segrè Daniel , Wilke Claus O.
Published: February 2014

A widely studied problem in systems biology is to predict bacterial phenotype from growth conditions, using mechanistic models such as flux balance analysis (FBA). However, the inverse prediction of growth conditions from phenotype is rarely considered. Here we develop a computational framework to carry out this inverse prediction on a computational model of bacterial metabolism. We use FBA to calculate bacterial phenotypes from growth conditions inE. coli, and then we assess how accurately we can predict the original growth conditions from the phenotypes. Prediction is carried out via regularized multinomial regression. Our analysis provides several important physiological and statistical insights. First, we show that by analyzing metabolic end products we can consistently predict growth conditions. Second, prediction is reliable even in the presence of small amounts of impurities. Third, flux through a relatively small number of reactions per growth source (~10) is sufficient for accurate prediction. Fourth, combining the predictions from two separate models, one trained only on carbon sources and one only on nitrogen sources, performs better than models trained to perform joint prediction. Finally, that separate predictions perform better than a more sophisticated joint prediction scheme suggests that carbon and nitrogen utilization pathways, despite jointly affecting cellular growth, may be fairly decoupled in terms of their dependence on specific assortments of molecular precursors.
Stress, heritability, tissue type and human methylome variation in mother-newborn dyads
Authors: Hughes David A. , Rodney Nicole C. , Mulligan Connie J.
Published: February 2014

DNA methylation variation has been implicated as a factor that influences inter-individual and inter-tissue phenotypic variation in numerous organisms and under various conditions. Here, using a unique collection of three tissues, derived from 24 mother-newborn dyads from war-torn Democratic Republic of Congo, we estimate how stress, heritability, tissue type and genomic/regulatory context influence genome-wide DNA methylation. We also evaluate if stress-associated variation may mediate an observed phenotype - newborn birthweight. On average, a minimal influence of stress and heritability are observed, while in contrast extensive among tissues and context dependency is evident. However, a notable overlap in heritable and stress-associated variation is observed and that variation is commonly correlated with birthweight variation. Finally, we observe that variation outside of promoter regions, particularly in enhancers, is far more dynamic across tissues and across conditions than in promoters, suggesting that variation outside of promoters may play a larger role in expression variation than variation found within promoter regions.
Separating Active and Passive Influences on Stomatal Control of Transpiration
Authors: McAdam Scott A.M. , Brodribb Timothy J.
Published: February 2014

Motivated by studies suggesting that the stomata of ferns and lycophytes do not conform to the standard active abscisic acid (ABA) -mediated stomatal control model, we examined stomatal behavior in a conifer species (Metasequoia glyptostroboides) that is phylogenetically midway between the fern and angiosperm clades. Similar to ferns, daytime stomatal closure in response to moderate water stress seemed to be a passive hydraulic process in M. glyptostroboides immediately alleviated by rehydrating excised shoots. Only after prolonged exposure to more extreme water stress did active ABA-mediated stomatal closure become important, because foliar ABA production was triggered after leaf turgor loss. The influence of foliar ABA on stomatal conductance and stomatal aperture was highly predictable and additive with the passive hydraulic influence. M. glyptostroboides thus occupies a stomatal behavior type intermediate between the passively controlled ferns and the characteristic ABA-dependent stomatal closure described in angiosperm herbs. These results highlight the importance of considering phylogeny as a major determinant of stomatal behavior.
The Rice TAL Effector–Dependent Resistance Protein XA10 Triggers Cell Death and Calcium Depletion in the Endoplasmic Reticulum
Authors: Tian Dongsheng , Wang Junxia , Zeng Xuan , Gu Keyu , Qiu Chengxiang , Yang Xiaobei , Zhou Zhiyun , Goh Meiling , Luo Yanchang , Murata-Hori Maki , White Frank F. , Yin Zhongchao
Published: February 2014

The recognition between disease resistance (R) genes in plants and their cognate avirulence (Avr) genes in pathogens can produce a hypersensitive response of localized programmed cell death. However, our knowledge of the early signaling events of the R gene–mediated hypersensitive response in plants remains limited. Here, we report the cloning and characterization of Xa10, a transcription activator–like (TAL) effector-dependent R gene for resistance to bacterial blight in rice (Oryza sativa). Xa10 contains a binding element for the TAL effector AvrXa10 (EBE  AvrXa10) in its promoter, and AvrXa10 specifically induces Xa10 expression. Expression of Xa10 induces programmed cell death in rice, Nicotiana benthamiana, and mammalian HeLa cells. The Xa10 gene product XA10 localizes as hexamers in the endoplasmic reticulum (ER) and is associated with ER Ca2+ depletion in plant and HeLa cells. XA10 variants that abolish programmed cell death and ER Ca2+ depletion in N. benthamiana and HeLa cells also abolish disease resistance in rice. We propose that XA10 is an inducible, intrinsic terminator protein that triggers programmed cell death by a conserved mechanism involving disruption of the ER and cellular Ca2+ homeostasis.
Cumulative Prospect Theory and Managerial Incentives for Fraudulent Financial Reporting
Authors: Fung Michael K.
Published: February 2014

Using samples of restating and nonrestating U.S. firms, the study empirically investigates the relationship between the incidence of fraudulent financial reporting and accounting‐based performance outcomes. The outcomes are framed as gains and losses relative to a reference point, defined as the mean performance of industry peers. Consistent with cumulative prospect theory (CPT), the findings show that fraud incidence is positively (negatively) related to the probability of a loss (gain); more (less) sensitive to the probability of a loss (gain) (i.e., loss‐aversion); and more (less) sensitive to an extra unit of the probability at a high‐ or low‐ (medium‐) probability level (i.e., nonlinear probability weighting function). The study extends the fraudulent financial reporting literature by formulating fraud incidence as a function of performance outcomes using peer performance as a reference point. By testing CPT's individual‐level behavioral implications on firm‐level archival data, the study reconceptualizes the investigation of fraudulent financial reporting in terms of risk attitude and extends prior investigations of CPT from laboratory experiments to a real‐world setting of fraudulent financial reporting.
Hedge Fund Intervention and Accounting Conservatism
Authors: Cheng C.S. Agnes , Huang Henry He , Li Yinghua
Published: February 2014

Hedge fund intervention has been associated with many positive corporate changes and is an important vehicle for informed shareholder monitoring. Effective monitoring has also been positively associated with accounting conservatism. Building upon these prior results, we predict an increase in accounting conservatism after hedge fund intervention. We use a large sample of hedge fund activist events and identify control firms with similar likelihoods of being targeted using the propensity score matching method to apply difference‐in‐difference tests. We find that when hedge fund activists have relatively large ownership and sufficient time to exert their monitoring power, target firms experience significant increases in conditional conservatism. CFO turnovers, upward/lateral auditor switches, and improvements in audit committee independence after intervention are accompanied by greater increases in conditional conservatism. Finally, we find greater increases in conditional conservatism when there is a lack of monitoring by dedicated institutional investors before the intervention. Our study suggests that hedge fund activists improve accounting monitoring tools and thus adds important new evidence on the effectiveness of shareholder monitoring on accounting practices.
Manganese superoxide dismutase plays an important role in the inflammatory process and predicts disease severity and activity in patients with ulcerative colitis
Authors: Ikumoto Taro , Hayashi Shinichi , Tomita Shigeki , Miwa Shigeharu , Mitomi Hiroyuki , Fujimori Takahiro , Imura Johji
Published: February 2014

The aim of this study was to investigate the expression pattern of manganese superoxide dismutase (MnSOD) in relation to inflammatory factors in ulcerative colitis (UC) and characterize this enzyme as a newly identified biomarker potentially linked to disease pathogenesis of UC. MnSOD expression was analyzed immunohistochemically in 48 formalin‐fixed and paraffin‐embedded specimens from patients with UC who had undergone endoscopical biopsy. MnSOD expression was observed in vascular endothelium, macrophages, and polymorphonuclear leukocytes within lamina propria of inflamed mucosa. The patients who did not express MnSOD tended to have stabilization of symptoms, but accompanied with status of inflammation. The MnSOD expression pattern was strongly correlated with disease type. MnSOD was expressed in polymorphonuclear leukocytes of all disease types, but cases of chronically counting and exacerbation type had particularly high frequency of immunopositive cells. MnSOD expression in macrophages was frequently observed in cases of symptom remaining type. The cases with MnSOD expression in the vascular endothelium showed a tendency to express in relapse‐remission and exacerbation of symptoms. Immunohistochemical evaluation for MnSOD expression may be useful for predicting disease severity and activity in patients with UC.
Mutational and expressional analysis of SMC2 gene in gastric and colorectal cancers with microsatellite instability
Authors: Je Eun Mi , Yoo Nam Jin , Lee Sug Hyung
Published: February 2014

Structural maintenance of chromosomes 2 (SMC2) gene encodes condensin complexes that are required for proper chromosome segregation and maintenance of chromosomal stability. Although cells with defective chromosome segregation become aneuploid and are prone to harbor chromosome instability, pathologic implications of SMC2 gene alterations are largely unknown. In a public database, we found that SMC2 gene had mononucleotide repeats that could be mutated in cancers with microsatellite instability (MSI). In this study, we analyzed these repeats in 32 gastric cancers (GC) with high MSI (MSI‐H), 59 GC with low MSI (MSI‐L)/stable MSI (MSS), 43 colorectal cancers (CRC) with MSI‐H and 60 CRC with MSI‐L/MSS by single‐strand conformation polymorphism (SSCP) and DNA sequencing. We also analyzed SMC2 protein expression in GC and CRC tissues using immunohistochemistry. We found SMC2 frameshift mutations in two GC and two CRC that would result in truncation of SMC2. The mutations were detected exclusively in MSI‐H cancers, but not in MSI‐L/MSS cancers. Loss of SMC2 expression was observed in 22% of GC and 25% of CRC. Of note, all of the cancers with SMC2 frameshift mutations displayed loss of SMC2 expression. Also, both GC and CRC with MSI‐H had significantly higher incidences in SMC2 frameshift mutations and loss of SMC2 expression than those with MSI‐L/MSS. Our data indicate that SMC2 gene is altered by both frameshift mutation and loss of expression in GC and CRC with MSI‐H, and suggest that SMC2 gene alterations might be involved in pathogenesis of these cancers.
Improving effect of Sivelestat on lipopolysaccharide‐induced lung injury in rats
Authors: Yuan Qing , Jiang Yan‐Wen , Fang Qiu‐Hong
Published: February 2014

Sepsis causes neutrophil sequestration in the lung, which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play an important role in the pathogenesis of ALI. This study investigated whether Sivelestat, a specific NE inhibitor, can attenuate ALI induced by lipopolysaccharide (LPS). In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Sivelestat treatments to induce ALI model. Lung injury was assessed by pulmonary histology, lung wet‐weight to dry‐weight (W/D) ratio, immunohistochemical analysis of intercellular adhesion molecule‐1 (ICAM‐1), the number of myeloperoxidase (MPO)‐positive cells, and gene expression of ICAM‐1. In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Sivelestat; nuclear factor‐κB (NF‐κB) p65 was measured by immunocytochemistry staining and Western blotting. Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, the number of MPO‐positive cells and enhanced expression of ICAM‐1 and ICAM‐1 gene. In vitro, the significant increased release of NF‐κB p65 and its subsequent translocation into the nucleus in PMVECs. In contrast, Sivelestat treatment significantly ameliorated the LPS‐induced lung injury, as judged by the marked improvement in all these indices. These results indicated that inhibition of NE attenuated LPS‐induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on NE.
Time until first dental caries for young children first seen in Federally Qualified Health Centers: a retrospective cohort study
Authors: Kuthy Raymond A. , Jones Michael , Kavand Golnaz , Momany Elizabeth , Askelson Natoshia , Chi Donald , Wehby George , Damiano Peter
Published: February 2014

Objectives

The study assessed the time until first dental caries for young children seen at five Federally Qualified Health Centers (FQHC) in Iowa and the relationship with the frequency and gaps (in months) of dental episodes, the number of topical fluoride treatments, and the number of dentists caring for the subject.

Methods

Forty children were randomly selected at each FQHC (n = 200). All children were continuously enrolled in the Medicaid program and had their first dental visit prior to age 6. Dental chart findings, claims data for the child and family, and birth certificate information were merged into one dataset. Dental visits were followed for a minimum of 36 months, including dental visits external to the FQHCs. Using time until first caries as the dependent variable, the data were subject to left, interval, and right censoring and were analyzed via Weibull regression.

Results

Slightly more than half of the 200 children experienced caries. Regression analysis indicated that the hazard of first dental caries increased by approximately 2% with each additional month that transpired between preventive recall examinations. In addition, children with older siblings who had a dental visit at the same center during the previous year prior to the subject's first visit were more likely to have a longer time until first dental caries.

Conclusions

Timing of dental care episodes was associated with caries experience in young children from low income families. Dental professionals should focus on regularity of dental care to prevent or delay caries experience in young children.
AJAP1 is Dysregulated at an Early Stage of Gliomagenesis and Suppresses Invasion Through Cytoskeleton Reorganization
Authors: Han Lei , Zhang Kai‐Liang , Zhang Jun‐Xia , Zeng Liang , Di Chun‐Hui , Fee Brian E. , Rivas Miriam , Bao Zhao‐Shi , Jiang Tao , Bigner Darrell , Kang Chun‐Sheng , Adamson David Cory
Published: February 2014

Aims

Down‐regulation of AJAP1 in glioblastoma multiforme (GBM) has been reported. However, the expression profiles of AJAP1 in gliomas and the underlying mechanisms of AJAP1 function on invasion are still poorly understood.

Methods

The gene profiles of AJAP1 in glioma patients were studied among four independent cohorts. Confocal imaging was used to analyze the AJAP1 localization. After AJAP1 overexpression in GBM cell lines, cellular polarity, cytoskeleton distribution, and antitumor effect were investigated in vitro and in vivo.

Results

AJAP1 expression was significantly decreased in gliomas compared with normal brain in REMBRANDT and CGCA cohorts. Additionally, low AJAP1 expression was associated with worse survival in GBMs in REMBRANDT and TCGA U133A cohorts and was significantly associated with classical and mesenchymal subtypes of GBMs among four cohorts. Confocal imaging indicated AJAP1 localized in cell membranes in low‐grade gliomas and AJAP1‐overexpressing GBM cells, but difficult to assess in high‐grade gliomas due to its absence. AJAP1 overexpression altered the cytoskeleton and cellular polarity in vitro and inhibited the tumor growth in vivo.

Conclusions

AJAP1 is dysregulated at an early stage of gliomagenesis and may suppress glioma cell invasion and proliferation, which suggests that AJAP1 may be a potential diagnostic and prognostic marker for gliomas.
Critically endangered island endemic or peripheral population of a widespread species? Conservation genetics ofKikuchi's gecko and the global challenge of protecting peripheral oceanic island endemic vertebrates
Authors: Siler Cameron D. , Oaks Jamie R. , Cobb Kerry , Ota Hidetoshi , Brown Rafe M.
Published: February 2014

Aim

To highlight the significant conservation challenge of evaluating peripheral endemic vertebrates in island archipelago systems and to assess empirically the complexities of approaches to conservation genetic studies across political and biogeographic boundaries. To demonstrate the poignant need for international collaboration and coordination when species delimitation problems with high conservation concern involve island endemics with biogeographically peripheral ranges.

Location

SoutheastAsia,LanyuIsland,Taiwan, and thePhilippines.

Methods

Genetic samples were collected and sequenced for one mitochondrial gene and five nuclear loci for species of theGekko mindorensis‐G. kikuchiispecies complex in Southeast Asia. We used maximum likelihood andBayesian phylogenetic methods and coalescent‐based species delimitation analyses to estimate phylogeographic relationships, construct multilocus haplotype networks and test putative species boundaries.

Results

Phylogenetic and population genetic analyses suggest thatKikuchi'sGecko may represent a peripheral population of a widespread species distributed from the northern Philippines to Taiwan. However, we identify a discrepancy between inferences of species boundaries resulting from methods based on allele frequencies versus coalescent‐based methods that incorporate evolutionary history. Coalescent‐based analyses suggest thatG. kikuchiimay be a distinct evolutionary lineage. Our study underscores the need for coalescent‐based methods in conjunction with population genetic approaches for conservation genetic assessments of widespread species.

Main conclusions

This study joins a few recent works suggesting thatPhilippine‐derived anomalies in the fauna ofLanyu (and possibly greaterTaiwan) are worthy of careful reconsideration. Determining whether each is the result of recent human‐mediated introduction or (possibly more ancient) natural dispersal should be the goal of future studies on this seldom‐conceived biogeographic relationship. Isolated species endemic to islands on the outer periphery of biogeographic and political regions represent particular conservation challenges. This is especially true if a species occurs on an isolated island that is allied biogeographically with one nation, but politically administered by another.
Predicting distribution changes of a mire ecosystem under future climates
Authors: Keith David A. , Elith Jane , Simpson Christopher C.
Published: February 2014

Aim

Mire ecosystems are threatened by global climate change but have important roles in biodiversity conservation, carbon storage, landscape‐scale hydrological function and in providing ecosystem services. We aimed to: (1) estimate change in areas environmentally suitable for mires under future climates; (2) evaluate the sensitivities of projected change to uncertainties in future climate and model structure; (3) evaluate the effect of global mitigation actions on distribution change; (4) identify potential climate refuges for future adaptation actions.

Methods

We developed and evaluated correlative bioclimatic models for an Australian mire ecosystem by: (1) selecting environmental predictors representing ecological processes that mediate ecosystem occurrence and dynamics; (2) using a high‐performance modelling algorithm; (3) quantifying predictive performance by cross‐validation; (4) cross‐checking responses to predictor variables between different algorithms; (5) comparing the modelled responses with expected mechanistic responses; (6) evaluating extrapolation risks by quantifying the deviation between future and current environmental domains of the study area and by assessing the temporal constancy of correlations between variables; (7) using a geographically stratified cross‐validation to verify spatial consistency of the model; and (8) quantifying the robustness of predictions of climate change impacts to uncertainty in both climate and ecological models.

Results

All combinations of global circulation models and distribution model projected declines of at least 30% in both area and suitability of environments for the mire ecosystem and in projecting a contraction of range to the southwest. We identified a likely refuge in the south of the distribution and two less certain, emerging areas of suitable environment west and south of the current distribution.

Main Conclusions

We conclude that southern mire ecosystems are highly susceptible to climate change. Our approach will be useful for the prediction of climate impacts on other ecosystems for which there is enough knowledge to map distributions and develop plausible hypotheses about environmental factors that influence them.
Implant dentistry in postgraduate university education. Present conditions, potential, limitations and future trends
Authors: Mattheos N. , Wismeijer D. , Shapira L.
Published: February 2014

Introduction

In recent years, opportunities for postgraduate university education in implant dentistry have increased significantly, with an increase in both the number but also the complexity of available postgraduate programmes. However, there appears to be a lack of standards directing the learning outcomes of such programmes.

Methods

A scientific literature search was conducted for publications reporting on university programmes within implant dentistry, including description of programmes and evaluation of learning outcomes. A separate Internet search was conducted to collect information on existing university programmes as presented on university websites.

Results

Implant dentistry has reached a critical mass of an independent, multidisciplinary and vibrant domain of science, which combines knowledge and discovery from many clinical and basic sciences. Many university programmes conclude with a master's or equivalent degree, but there appears to be a great diversity with regard to duration and learning objectives, as well as targeted skills and competences. The importance of implant dentistry has also increased within established specialist training programmes. There was little indication, however, that the comprehensive aspects of implant dentistry are present in all specialist training programmes where implants are being covered.

Conclusions

Although universities should maintain the options of designing academic programmes as they best see fit, it is imperative for them to introduce some form of transparent and comparable criteria, which will allow the profession and the public to relate the degree and academic credentials to the actual skills and competences of the degree holder. With regard to established specialist training programmes, the interdisciplinary and comprehensive nature of implant dentistry needs to be emphasised, covering both surgical and restorative aspects. Finally, implant dentistry is not, at present, a dental specialty. The profession has not reached a consensus as to whether the introduction of a new recognised specialist field is either necessary or desired.
Developing implant dentistry education in Europe: the continuum from undergraduate to postgraduate education and continuing professional development
Authors: Mattheos N. , de Bruyn H. , Hultin M. , Jepsen S. , Klinge B. , Koole S. , Sanz M. , Ucer C. , Lang N. P.
Published: February 2014

Introduction

Implant dentistry is a treatment modality which has mainstream clinical practice of comprehensive care, which however is not adequately represented in the undergraduate dental curricula. A consensus workshop organised by ADEE in 2008, set the benchmarks for the knowledge and competences a modern dental practitioner must possess with regard to implant dentistry, as well as defined undergraduate and postgraduate pathways for the acquisition of these competences. Today, 5 years later, there exist several challenges for the implementation of these benchmarks in both undergraduate curricula but also post‐graduation educational pathways.

Methods

A consensus workshop was organised by ADEE, bringing together 48 opinion leaders, including academic teachers of all disciplines related to implant dentistry, specialists, representatives of relevant scientific and professional associations, as well as industry delegates. The objectives of the workshop were to evaluate the existing scientific literature, reported experience and best practices in order to identify potential and limitations for the implementation of implant dentistry in the undergraduate curriculum, as well produce recommendations for the optimal educational structures for postgraduate programmes and continuing professional development.

Results

The scientific committee conducted two European‐wide questionnaire surveys to better document the current state of education in implant dentistry. Upon completion of the surveys, reviewers were appointed to produce three scientific review papers, identifying current achievements and future challenges. Finally, during the 3 days of the workshop, all the evidence was reviewed and the main conclusions and recommendations that were adopted by all participants are reported in the present Consensus Paper.

Conclusions

Implementation of implant dentistry in the undergraduate curriculum has improved significantly, but still lags behind the benchmarks set in 2008 and the diversity between institutions remains big. At the post‐graduation level, there is currently a wide diversity of courses and pathways towards competences related to implant dentistry and there is at present a great need for quality assurance, as well as standardisation and transparency of the learning outcomes.