bluuebunny/crossref_metadata_2025 huggingface dataset:
Remarkable Decline in Ischemic Stroke Mortality is Not Matched by Changes in Incidence
Authors: Vaartjes Ilonca , O’Flaherty Martin , Capewell Simon , Kappelle Jaap , Bots Michiel
Published: December 2012

Background and Purpose—

In Western Europe, mortality from ischemic stroke (IS) has declined over several decades. Age–sex-specific IS mortality, IS incidence, 30-day case fatality, and 1-year mortality after hospital admission are essential for explaining recent trends in IS mortality in the new millennium.

Methods—

Data for all IS deaths (1980–2010) in the Netherlands were grouped by year, sex, and age. A joinpoint regression was fitted to detect points in time at which significant changes in the trends occur. By linking nationwide registers, a cohort of patients first admitted for IS between 1997 and 2005 was constructed and age–sex-specific 30-day case fatality and 1-year mortality were computed. IS incidence (admitted IS patients and out-of-hospital IS deaths) was computed by age and sex. Mann–Kendall tests were used for trend evaluation.

Results—

IS mortality declined continuously between1980 and 2000 with an attenuation of decline in the 1990s in some of the age–sex groups. A remarkable decline in IS mortality after 2000 was observed in all age–sex groups, except for young men. An improved decline in 30-day case fatality and in 1-year mortality was also observed in almost all age–sex groups. In contrast, IS incidence remained stable between 1997 and 2005 or even increased slightly.

Conclusions—

The recent remarkable decline in IS mortality was not matched by a decline in the number of incident nonfatal IS events. This is worrying, because IS is already a leading cause of adult disability, claiming a heavy human and economic burden. Prevention of IS is therefore now of the greatest importance.
A Modeling Study of Stratospheric Waves over the Southern Andes and Drake Passage
Authors: Jiang Qingfang , Doyle James D. , Reinecke Alex , Smith Ronald B. , Eckermann Stephen D.
Published: December 2012

Large-amplitude stratospheric gravity waves over the southern Andes and Drake Passage, as observed by the Atmospheric Infrared Sounder (AIRS) on 8–9 August 2010, are modeled and studied using a deep (0–70 km) version of the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) model. The simulated tropospheric waves are generated by flow over the high central Andes ridge and the Patagonian peaks in the southern Andes. Some waves emanating from Patagonia propagate southeastward across Drake Passage into the stratosphere over a horizontal distance of more than 1000 km. The wave momentum flux is characterized by a tropospheric maximum over Patagonia that splits into two comparable maxima in the stratosphere: one located directly over the terrain and the other tilting southward with altitude.

Using spatial ray-tracing techniques and flow conditions derived from the numerical simulation, the authors find that waves that originate from the high ridge in the Central Andes are absorbed by a critical level in the lower stratosphere. The three-dimensional waves originating from Patagonia could be separated into three families—namely, a northeast-propagating family, which is absorbed by a critical level between 15 and 20 km; a localized family, which breaks down in the stratosphere and lower mesosphere directly above Patagonia; and a southeast-propagating family, which forms the observed linear stratospheric wave patterns oriented across Drake Passage. The southward group propagation, assisted by lateral wave refraction due to persistent meridional shear of the zonal winds, leads to stratospheric wave breaking and drag near 60°S, well south of the parent orography.
Challenges in Forecasting the 2011 Runoff Season in the Colorado Basin
Authors: Werner Kevin , Yeager Kristen
Published: December 2012

Historically large snowpack across the upper Colorado basin and the Great Basin in 2011 presented the potential for widespread and severe flooding. While widespread flooding did occur, its impacts were largely moderated through a combination of sustained cool weather during the melt season and mitigation measures based on forecasts. The potential for more severe flooding persisted from April through the first part of July as record-high snowpacks slowly melted. NOAA's Colorado Basin River Forecast Center (CBRFC) is the primary office responsible for generating river forecasts in support of emergency and water management within the Colorado River basin. This paper describes the 2011 runoff season in the basin and examines the skill of CBRFC forecasts for that season. The primary goal of this paper is to raise awareness of the research and development areas that could, if successfully integrated into the CBRFC river forecasting system, improve forecasts in similar situations in the future. The authors identify three areas of potential forecast improvement: 1) improving week two to seasonal weather and climate predictions, 2) incorporation of remotely sensed snow-covered area, and 3) improving coordination between reservoir operations and forecasts.
Real-Time Hazard Approximation of Long-Lasting Convective Storms Using Emergency Data
Authors: Rossi Pekka J. , Hasu Vesa , Halmevaara Kalle , Mäkelä Antti , Koistinen Jarmo , Pohjola Heikki
Published: December 2012

Convective storms cause several types of damage, including economic and ecological losses, every year. This paper focuses on an automatic hazard-level determination of convective storms based on a largely unused information source: real-time emergency report data. In addition to the location of the report, the emergency response centers classify cases into different emergency types and deliver a free-form verbal description of the incident for online use. This study uses archived weather-related emergency reports to determine hazard levels for convective storms detected by the weather radar. To develop an algorithm for estimating the hazard level of convective storms, a weather radar–databased convective storm-tracking algorithm was applied with a method that links reported emergency events to individually tracked convective storms. Based on the relationship between each convective storm track and an emergency report, the algorithm determines the hazard level of the storms automatically. Moreover, the developed algorithm takes into account the population density at the location of the report because, in densely populated areas, the flow of emergency reports is more intense. The proposed algorithm with case studies shows the potential use of real-time emergency call data in operational severe weather nowcasting and warning tools. This study demonstrates that supplementing storms with emergency information is advantageous, especially with long-lasting storms such as supercell storms or mesoscale convective systems.
Sensitivity of Simulated Climate to Two Atmospheric Models: Interpretation of Differences between Dry Models and Moist Models
Authors: Zhang He , Zhang Minghua , Zeng Qing-cun
Published: December 2012

The dynamical core of the Institute of Atmospheric Physics of the Chinese Academy of Sciences Atmospheric General Circulation Model (IAP AGCM) and the Eulerian spectral transform dynamical core of the Community Atmosphere Model, version 3.1 (CAM3.1), developed at the National Center for Atmospheric Research (NCAR) are used to study the sensitivity of simulated climate. The authors report that when the dynamical cores are used with the same CAM3.1 physical parameterizations of comparable resolutions, the model with the IAP dynamical core simulated a colder troposphere than that from the CAM3.1 core, reducing the CAM3.1 warm bias in the tropical and midlatitude troposphere. However, when the two dynamical cores are used in the idealized Held–Suarez tests without moisture physics, the IAP AGCM core simulated a warmer troposphere than that in CAM3.1. The causes of the differences in the full models and in the dry models are then investigated.

The authors show that the IAP dynamical core simulated weaker eddies in both the full physics and the dry models than those in the CAM due to different numerical approximations. In the dry IAP model, the weaker eddies cause smaller heat loss from poleward dynamical transport and thus warmer troposphere in the tropics and midlatitudes. When moist physics is included, however, weaker eddies also lead to weaker transport of water vapor and reduction of high clouds in the IAP model, which then causes a colder troposphere due to reduced greenhouse warming of these clouds. These results show how interactive physical processes can change the effect of a dynamical core on climate simulations between two models.
Using Electronic Storybooks to Support Word Learning in Children With Severe Language Impairments
Authors: Smeets Daisy J. H. , van Dijken Marianne J. , Bus Adriana G.
Published: December 2012

Novel word learning is reported to be problematic for children with severe language impairments (SLI). In this study, we tested electronic storybooks as a tool to support vocabulary acquisition in SLI children. In Experiment 1, 29 kindergarten SLI children heard four e-books each four times: (a) two stories were presented as video books with motion pictures, music, and sounds, and (b) two stories included only static illustrations without music or sounds. Two other stories served as the control condition. Both static and video books were effective in increasing knowledge of unknown words, but static books were most effective. Experiment 2 was designed to examine which elements in video books interfere with word learning: video images or music or sounds. A total of 23 kindergarten SLI children heard 8 storybooks each four times: (a) two static stories without music or sounds, (b) two static stories with music or sounds, (c) two video stories without music or sounds, and (d) two video books with music or sounds. Video images and static illustrations were equally effective, but the presence of music or sounds moderated word learning. In children with severe SLI, background music interfered with learning. Problems with speech perception in noisy conditions may be an underlying factor of SLI and should be considered in selecting teaching aids and learning environments.
Cry1−/− Circadian Rhythmicity Depends on SCN Intercellular Coupling
Authors: Evans Jennifer A. , Pan Haiyun , Liu Andrew C. , Welsh David K.
Published: December 2012

In mammals, the suprachiasmatic nucleus (SCN) is the central pacemaker organizing circadian rhythms of behavior and physiology. At the cellular level, the mammalian clock consists of autoregulatory feedback loops involving a set of “clock genes,” including the Cryptochrome ( Cry) genes, Cry1 and Cry2. Experimental evidence suggests that Cry1 and Cry2 play distinct roles in circadian clock function. In mice, Cry1 is required for sustained circadian rhythms in dissociated SCN neurons or fibroblasts but not in organotypic SCN slices or at the behavioral level, whereas Cry2 is not required at any of these levels. It has been argued that coupling among SCN cellular oscillators compensates for clock gene defects to preserve oscillatory function. Here we test this hypothesis in Cry1−/− mice by first disrupting intercellular coupling in vivo using constant light (resulting in behavioral arrhythmicity) and then examining circadian clock gene expression in SCN slices at the single cell level. In this manner, we were able to test the role of intercellular coupling without drugs and while preserving tissue organization, avoiding the confounding influences of more invasive manipulations. Cry1−/− mice (as well as control Cry2−/− mice) bearing the PER2::LUC knock-in reporter were transferred from a standard light:dark cycle to constant bright light (~650 lux) to induce arrhythmic locomotor patterns. In SCN slices from these animals, we used bioluminescence imaging to monitor PER2::LUC expression in single cells. We show that SCN slices from rhythmic Cry1−/− and Cry2−/− mice had similarly high percentages of functional single-cell oscillators. In contrast, SCN slices from arrhythmic Cry1−/− mice had significantly fewer rhythmic cells than SCN slices from arrhythmic Cry2−/− mice. Thus, constant light in vivo disrupted intercellular SCN coupling to reveal a cell-autonomous circadian defect in Cry1−/− cells that is normally compensated by intercellular coupling in vivo.
Pigment-Dispersing Factor Is Involved in Age-Dependent Rhythm Changes in Drosophila melanogaster
Authors: Umezaki Yujiro , Yoshii Taishi , Kawaguchi Tomoaki , Helfrich-Förster Charlotte , Tomioka Kenji
Published: December 2012

Most animals show rest/activity rhythms that are regulated by an endogenous timing mechanism, the so-called circadian system. The rhythm becomes weaker with age, but the mechanism underlying the age-associated rhythm change remains to be elucidated. Here we employed Drosophila melanogaster as a model organism to study the aging effects on the rhythm. We first investigated activity rhythms under light-dark (LD) cycles and constant darkness (DD) in young (1-day-old) and middle-aged (30-, 40-, and 50-day-old) wild-type male flies. The middle-aged flies showed a reduced activity level in comparison with young flies. Additionally, the free-running period significantly lengthened in DD, and the rhythm strength was diminished. Immunohistochemistry against pigment-dispersing factor (PDF), a principal neurotransmitter of the Drosophila clock, revealed that PDF levels declined with age. We also found an attenuation of TIMELESS (TIM) oscillation in the cerebral clock neurons in elder flies. Intriguingly, overexpression of PDF suppressed age-associated changes not only in the period and strength of free-running locomotor rhythms but also in the amplitude of TIM oscillations in many pacemaker neurons in the elder flies, suggesting that the age-dependent PDF decline is responsible for the rhythm attenuation. These results suggest that the age-associated reduction of PDF may cause attenuation of intercellular communication in the circadian neuronal network and of TIM cycling, which may result in the age-related rhythm decay.
Design and analysis of bubble-injected water ramjets with discrete injection configurations by computational fluid dynamics method
Authors: Hayati Arash Nemati , Hashemi Seyed Mohammad , Shams Mehrzad
Published: December 2012

In this study, the performance of a typical bubbly water ramjet was investigated by the application of computational fluid dynamics method at different vessel velocities up to 80 knots for a range of air mass flow rates up to 0.9 kg/s. For this purpose, the validity of presented method was preliminarily examined for a converging–diverging nozzle. Then, a designed ramjet with discrete injection configuration was studied at different operating conditions. It was proved that the injection process significantly increases the amount of generated thrust up to 10 times more than the thrust of a single-phase water ramjet. The results suggest that for optimum operation of the ramjet, specific values should be assigned for both inlet and mixing chamber diameters with respect to outlet diameter. Furthermore, it seems that the modification of mixing chamber profile can effectively improve the performance, as the generated thrust of model with throat-like chamber surpasses that for conventional model up to more than two times. Finally, in order to rectify the contradiction of results obtained in previous literatures on the dependency of thrust on vessel velocity, a meaningful relation was derived between the generated thrust of the ramjet with the advance velocity at different air mass flow rates.
The Development of an Experimental Model of Contaminated Muscle Injury in Rabbits
Authors: Eardley Will G. P. , Martin Kevin R. , Taylor Chris , Kirkman Emrys , Clasper Jon C. , Watts Sarah A.
Published: December 2012

Extent of tissue trauma and contamination determine outcome in extremity injury. In contrast to fracture, osteomyelitis, and closed muscle injury studies, there are limited small animal models of extremity muscle trauma and contamination. To address this we developed a model of contaminated muscle injury in rabbits. Twenty-eight anesthetized New Zealand White rabbits underwent open controlled injury of the flexor carpi ulnaris (FCU). Twenty-two animals had subsequent contamination of the injured muscle with Staphylococcus aureus. All animals were sacrificed at 48 hours and the level of muscle injury and contamination determined by quantitative histological and microbiological analysis. A 1-kg mass dropped 300 mm onto the mobilized FCU resulted in localized necrosis of the muscle belly. Delivery of a mean challenge of 3.71 × 106 cfu/100 µL S aureus by droplet spread onto the injured muscle produced a muscle contamination of 8.79 × 106 cfu/g at 48 hours. Ipsilateral axillary lymph nodes demonstrated clinically significant activation. All animals had normal body temperature and hematological parameters throughout and blood and urinalysis culture at autopsy were negative for organisms. This model allows reproducible muscle injury and contamination with the organism ubiquitous to extremity wound infection at a level sufficient to allow quantitative assessment of subsequent wound care interventions without incurring systemic involvement.
The discursive reproduction of ideologies and national identities in the Chinese and Japanese English-language press
Authors: Chan Michael
Published: December 2012

Using critical discourse analysis this study analyzes how ideologies and national identities are discursively constructed through editorial and opinion commentaries in two English-language newspapers from China and Japan on an international incident involving the two countries. The first four editorials/opinions on the East China Sea trawler collision incident from the China Daily and Daily Yomiuri are analyzed. Findings show that a variety of discursive strategies are adopted by the newspapers to construct national identity and intergroup relations, including: 1) the discursive categorization of group identity, 2) the discursive re-categorization of intergroup relations, and 3) the discursive re-categorization of intragroup relations. Even though both newspapers are products of globalization, and purport to target international and cosmopolitan audiences, the reporting of the East China Sea incident closely adheres to official narratives and discourses of the respective governments.
Discourses of silence: The construction of ‘otherness’ in family planning pamphlets
Authors: Makoni Busi
Published: December 2012

This article explores verbal and visual language use in Zimbabwean contraceptive promotional brochures distributed from the early to mid-1980s. Drawing on recent work in critical discourse analysis of text and visual design, the article uses multimodal discourse analysis and draws from Halliday’s Systemic Functional Grammar’s transitivity analysis to analyze family planning pamphlets, focusing on the discursive construction of women as contraceptive users. The article argues that the salience of the language of risk and vulnerability, which is textually and visually deployed throughout the pamphlets, discursively constructs risk as a feature of unequal power relations. The article further argues that underlying the overarching discourse on risk are multiple ‘silences’ that discursively construct an ideological difference consisting of oppositional binaries between ‘us’ and ‘them’ in terms of power relations. The differentiation of social groups reflects ‘hidden’ social inequalities in the text and visual images.
Cultural Differences in the Link Between Supportive Relationships and Proinflammatory Cytokines
Authors: Chiang Jessica J. , Saphire-Bernstein Shimon , Kim Heejung S. , Sherman David K. , Taylor Shelley E.
Published: December 2012

Research suggests that inflammation may partially mediate the link between supportiveness of social relationships and physical health. However, cultural differences between Asians and European Americans in the nature of relationships and in seeking social support suggest that there may be cultural differences in the relation between supportive relationships and proinflammatory activity. One hundred and twenty-one young adult participants completed assessments of support from their close relationships (parents, romantic partner, and close friends) and provided oral mucosal transudate samples for assessment of the proinflammatory cytokines interleukin-6 (IL-6) and the type II soluble receptor for tumor necrosis factor-α (sTNFαRII). As predicted, more supportive relationships were related to lower levels of IL-6 among European Americans, but not among Asian Americans. There were no relations to sTNFαRII in either group. We conclude that associations between supportive relationships and inflammatory activity may differ in ways that reflect cultural differences in the construal of relationships and social support.
PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells
Authors: Yuki Hiromichi , Ueno Shikiko , Tatetsu Hiro , Niiro Hiroaki , Iino Tadafumi , Endo Shinya , Kawano Yawara , Komohara Yoshihiro , Takeya Motohiro , Hata Hiroyuki , Okada Seiji , Watanabe Toshiki , Akashi Koichi , Mitsuya Hiroaki , Okuno Yutaka
Published: December 2012

Key Points

PU.1 is a potent tumor suppressor in cHL cells and the induction of PU.1 is a possible therapeutic option for patients with cHL.
q-analogue of a new sequence of linear positive operators
Authors: Gupta Vijay , Kim Taekyun , Lee Sang-Hun
Published: December 2012

This paper deals with Durrmeyer type generalization of q-Baskakov type operators using the concept of q-integral, which introduces a new sequence of positive q-integral operators. We show that this sequence is an approximation process in the polynomial weighted space of continuous functions defined on the interval

[
0
,
∞
)

. An estimate for the rate of convergence and weighted approximation properties are also obtained.

MSC:41A25, 41A36.
Efficient error correction algorithms for gene tree reconciliation based on duplication, duplication and loss, and deep coalescence
Authors: Chaudhary Ruchi , Burleigh J Gordon , Eulenstein Oliver
Published: December 2012

Background

Gene tree - species tree reconciliation problems infer the patterns and processes of gene evolution within a species tree. Gene tree parsimony approaches seek the evolutionary scenario that implies the fewest gene duplications, duplications and losses, or deep coalescence (incomplete lineage sorting) events needed to reconcile a gene tree and a species tree. While a gene tree parsimony approach can be informative about genome evolution and phylogenetics, error in gene trees can profoundly bias the results.

Results

We introduce efficient algorithms that rapidly search local Subtree Prune and Regraft (SPR) or Tree Bisection and Reconnection (TBR) neighborhoods of a given gene tree to identify a topology that implies the fewest duplications, duplication and losses, or deep coalescence events. These algorithms improve on the current solutions by a factor of n for searching SPR neighborhoods and n
2 for searching TBR neighborhoods, where n is the number of taxa in the given gene tree. They provide a fast error correction protocol for ameliorating the effects of gene tree error by allowing small rearrangements in the topology to improve the reconciliation cost. We also demonstrate a simple protocol to use the gene rearrangement algorithm to improve gene tree parsimony phylogenetic analyses.

Conclusions

The new gene tree rearrangement algorithms provide a fast method to address gene tree error. They do not make assumptions about the underlying processes of genome evolution, and they are amenable to analyses of large-scale genomic data sets. These algorithms are also easily incorporated into gene tree parsimony phylogenetic analyses, potentially producing more credible estimates of reconciliation cost.
Transcriptome profile of a bovine respiratory disease pathogen: Mannheimia haemolytica PHL213
Authors: Reddy Joseph S , Kumar Ranjit , Watt James M , Lawrence Mark L , Burgess Shane C , Nanduri Bindu
Published: December 2012

Background

Computational methods for structural gene annotation have propelled gene discovery but face certain drawbacks with regards to prokaryotic genome annotation. Identification of transcriptional start sites, demarcating overlapping gene boundaries, and identifying regulatory elements such as small RNA are not accurate using these approaches. In this study, we re-visit the structural annotation of Mannheimia haemolytica PHL213, a bovine respiratory disease pathogen. M. haemolytica is one of the causative agents of bovine respiratory disease that results in about $3 billion annual losses to the cattle industry. We used RNA-Seq and analyzed the data using freely-available computational methods and resources. The aim was to identify previously unannotated regions of the genome using RNA-Seq based expression profile to complement the existing annotation of this pathogen.

Results

Using the Illumina Genome Analyzer, we generated 9,055,826 reads (average length ~76 bp) and aligned them to the reference genome using Bowtie. The transcribed regions were analyzed using SAMTOOLS and custom Perl scripts in conjunction with BLAST searches and available gene annotation information. The single nucleotide resolution map enabled the identification of 14 novel protein coding regions as well as 44 potential novel sRNA. The basal transcription profile revealed that 2,506 of the 2,837 annotated regions were expressed in vitro, at 95.25% coverage, representing all broad functional gene categories in the genome. The expression profile also helped identify 518 potential operon structures involving 1,086 co-expressed pairs. We also identified 11 proteins with mutated/alternate start codons.

Conclusions

The application of RNA-Seq based transcriptome profiling to structural gene annotation helped correct existing annotation errors and identify potential novel protein coding regions and sRNA. We used computational tools to predict regulatory elements such as promoters and terminators associated with the novel expressed regions for further characterization of these novel functional elements. Our study complements the existing structural annotation of Mannheimia haemolytica PHL213 based on experimental evidence. Given the role of sRNA in virulence gene regulation and stress response, potential novel sRNA described in this study can form the framework for future studies to determine the role of sRNA, if any, in M. haemolytica pathogenesis.
A statistical model-building perspective to identification of MS/MS spectra with PeptideProphet
Authors: Ma Kelvin , Vitek Olga , Nesvizhskii Alexey I
Published: December 2012

PeptideProphet is a post-processing algorithm designed to evaluate the confidence in identifications of MS/MS spectra returned by a database search. In this manuscript we describe the "what and how" of PeptideProphet in a manner aimed at statisticians and life scientists who would like to gain a more in-depth understanding of the underlying statistical modeling. The theory and rationale behind the mixture-modeling approach taken by PeptideProphet is discussed from a statistical model-building perspective followed by a description of how a model can be used to express confidence in the identification of individual peptides or sets of peptides. We also demonstrate how to evaluate the quality of model fit and select an appropriate model from several available alternatives. We illustrate the use of PeptideProphet in association with the Trans-Proteomic Pipeline, a free suite of software used for protein identification.
Modeling and mining term association for improving biomedical information retrieval performance
Authors: Hu Qinmin , Huang Jimmy Xiangji , Hu Xiaohua
Published: December 2012

Background

The growth of the biomedical information requires most information retrieval systems to provide short and specific answers in response to complex user queries. Semantic information in the form of free text that is structured in a way makes it straightforward for humans to read but more difficult for computers to interpret automatically and search efficiently. One of the reasons is that most traditional information retrieval models assume terms are conditionally independent given a document/passage. Therefore, we are motivated to consider term associations within different contexts to help the models understand semantic information and use it for improving biomedical information retrieval performance.

Results

We propose a term association approach to discover term associations among the keywords from a query. The experiments are conducted on the TREC 2004-2007 Genomics data sets and the TREC 2004 HARD data set. The proposed approach is promising and achieves superiority over the baselines and the GSP results. The parameter settings and different indices are investigated that the sentence-based index produces the best results in terms of the document-level, the word-based index for the best results in terms of the passage-level and the paragraph-based index for the best results in terms of the passage2-level. Furthermore, the best term association results always come from the best baseline. The tuning number k in the proposed recursive re-ranking algorithm is discussed and locally optimized to be 10.

Conclusions

First, modelling term association for improving biomedical information retrieval using factor analysis, is one of the major contributions in our work. Second, the experiments confirm that term association considering co-occurrence and dependency among the keywords can produce better results than the baselines treating the keywords independently. Third, the baselines are re-ranked according to the importance and reliance of latent factors behind term associations. These latent factors are decided by the proposed model and their term appearances in the first round retrieved passages.
Identification of novel MiRNAs and MiRNA expression profiling during grain development in indica rice
Authors: Lan Ying , Su Ning , Shen Yi , Zhang Rongzhi , Wu Fuqing , Cheng Zhijun , Wang Jiulin , Zhang Xin , Guo Xiupin , Lei Cailin , Wang Jie , Jiang Ling , Mao Long , Wan Jianmin
Published: December 2012

Background

MicroRNAs (miRNAs) modulate gene expression in different tissues and at diverse developmental stages, including grain development in japonica rice. To identify novel miRNAs in indica rice and to study their expression patterns during the entire grain filling process, small RNAs from all stages of grain development were sequenced and their expression patterns were studied using customized miRNA chips.

Results

A total of 21 conserved and 91 non-conserved miRNA families were found in developing indica grains. We also discovered 11 potential novel miRNAs based on the presence of their miRNA*s. Expression patterns of these identified miRNAs were analyzed using customized miRNA chips. The results showed that during the filling phase about half of the detected miRNAs were up-regulated, whereas the remainder were down-regulated. Predicted targets of differentially expressed miRNAs may participate in carbohydrate metabolism, hormone signaling and pathways associated with seed maturity, suggesting potentially important roles in rice grain development.

Conclusions

This study is the first genome-wide investigation of miRNAs during the grain-filling phase of an indica variety of rice. The novel miRNAs identified might be involved in new miRNA regulatory pathways for grain development. The complexity of these miRNAs and their targets and interactions require further study to obtain a better understanding of the molecular mechanisms underlying grain development.
The complete swine olfactory subgenome: expansion of the olfactory gene repertoire in the pig genome
Authors: Nguyen Dinh Truong , Lee Kyooyeol , Choi Hojun , Choi Min-kyeung , Le Minh Thong , Song Ning , Kim Jin-Hoi , Seo Han Geuk , Oh Jae-Wook , Lee Kyungtae , Kim Tae-Hun , Park Chankyu
Published: December 2012

Background

Insects and animals can recognize surrounding environments by detecting thousands of chemical odorants. Olfaction is a complicated process that begins in the olfactory epithelium with the specific binding of volatile odorant molecules to dedicated olfactory receptors (ORs). OR proteins are encoded by the largest gene superfamily in the mammalian genome.

Results

We report here the whole genome analysis of the olfactory receptor genes of S. scrofa using conserved OR gene specific motifs and known OR protein sequences from diverse species. We identified 1,301 OR related sequences from the S. scrofa genome assembly, Sscrofa10.2, including 1,113 functional OR genes and 188 pseudogenes. OR genes were located in 46 different regions on 16 pig chromosomes. We classified the ORs into 17 families, three Class I and 14 Class II families, and further grouped them into 349 subfamilies. We also identified inter- and intra-chromosomal duplications of OR genes residing on 11 chromosomes. A significant number of pig OR genes (n = 212) showed less than 60% amino acid sequence similarity to known OR genes of other species.

Conclusion

As the genome assembly Sscrofa10.2 covers 99.9% of the pig genome, our analysis represents an almost complete OR gene repertoire from an individual pig genome. We show that S. scrofa has one of the largest OR repertoires, suggesting an expansion of OR genes in the swine genome. A significant number of unique OR genes in the pig genome may suggest the presence of swine specific olfactory stimulation.
Boolean modeling and fault diagnosis in oxidative stress response
Authors: Sridharan Sriram , Layek Ritwik , Datta Aniruddha , Venkatraj Jijayanagaram
Published: December 2012

Background

Oxidative stress is a consequence of normal and abnormal cellular metabolism and is linked to the development of human diseases. The effective functioning of the pathway responding to oxidative stress protects the cellular DNA against oxidative damage; conversely the failure of the oxidative stress response mechanism can induce aberrant cellular behavior leading to diseases such as neurodegenerative disorders and cancer. Thus, understanding the normal signaling present in oxidative stress response pathways and determining possible signaling alterations leading to disease could provide us with useful pointers for therapeutic purposes. Using knowledge of oxidative stress response pathways from the literature, we developed a Boolean network model whose simulated behavior is consistent with earlier experimental observations from the literature. Concatenating the oxidative stress response pathways with thePI3-Kinase-Aktpathway, the oxidative stress is linked to the phenotype of apoptosis, once again through a Boolean network model. Furthermore, we present an approach for pinpointing possible fault locations by using temporal variations in the oxidative stress input and observing the resulting deviations in the apoptotic signature from the normally predicted pathway. Such an approach could potentially form the basis for designing more effective combination therapies against complex diseases such as cancer.

Results

In this paper, we have developed a Boolean network model for the oxidative stress response. This model was developed based on pathway information from the current literature pertaining to oxidative stress. Where applicable, the behaviour predicted by the model is in agreement with experimental observations from the published literature. We have also linked the oxidative stress response to the phenomenon of apoptosis via thePI3k/Aktpathway.

Conclusions

It is our hope that some of the additional predictions here, such as those pertaining to the oscillatory behaviour of certain genes in the presence of oxidative stress, will be experimentally validated in the near future. Of course, it should be pointed out that the theoretical procedure presented here for pinpointing fault locations in a biological network with feedback will need to be further simplified before it can be even considered for practical biological validation.
SPRR2A enhances p53 deacetylation through HDAC1 and down regulates p21 promoter activity
Authors: Mizuguchi Yoshiaki , Specht Susan , Lunz John G , Isse Kumiko , Corbitt Natasha , Takizawa Toshihiro , Demetris Anthony J
Published: December 2012

Background

Small proline rich protein (SPRR) 2A is one of 14 SPRR genes that encodes for a skin cross-linking protein, which confers structural integrity to the cornified keratinocyte cell envelope. New evidence, however, shows that SPRR2A is also a critical stress and wound repair modulator: it enables a variety of barrier epithelia to transiently acquire mesenchymal characteristics (EMT) and simultaneously quench reactive oxygen species during wound repair responses. p53 is also widely recognized as the node in cellular stress responses that inhibits EMT and triggers cell-cycle arrest, apoptosis, and cellular senescence. Since some p53-directed processes would seem to impede wound repair of barrier epithelia, we hypothesized that SPRR2A up regulation might counteract these effects and enable/promote wound repair under stressful environmental conditions.

Results

Using a well characterized cholangiocarcinoma cell line we show that levels of SPRR2A expression, similar to that seen during stressful biliary wound repair responses, disrupts acetylation and subsequent p53 transcriptional activity. p53 deacetylation is accomplished via two distinct, but possibly related, mechanisms: 1) a reduction of p300 acetylation, thereby interfering with p300-p53 binding and subsequent p300 acetylation of K382 in p53; and 2) an increase in histone deacetylase 1 (HDAC1) mRNA and protein expression. The p300 CH3 domain is essential for both the autoacetylation of p300 and transference of the acetyl group to p53 and HDAC1 is a component of several non-p300 complexes that enhance p53 deacetylation, ubiquitination, and proteosomal degradation. HDAC1 can also bind the p300-CH3 domain, regulating p300 acetylation and interfering with p300 mediated p53 acetylation. The importance of this pathway is illustrated by showing complete restoration of p53 acetylation and partial restoration of p300 acetylation by treating SPRR2A expressing cells with HDAC1 siRNA.

Conclusion

Up-regulation of SPRR2A, similar to that seen during barrier epithelia wound repair responses reduces p53 acetylation by interfering with p300-p53 interactions and by increasing HDAC1 expression. SPRR2A, therefore, functions as a suppressor of p53-dependent transcriptional activity, which otherwise might impede cellular processes needed for epithelial wound repair responses such as EMT.
Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection
Authors: Moriichi Kentaro , Fujiya Mikihiro , Sato Ryu , Watari Jiro , Nomura Yoshiki , Nata Toshie , Ueno Nobuhiro , Maeda Shigeaki , Kashima Shin , Itabashi Kentaro , Ishikawa Chisato , Inaba Yuhei , Ito Takahiro , Okamoto Kotaro , Tanabe Hiroki , Mizukami Yusuke , Saitoh Yusuke , Kohgo Yutaka
Published: December 2012

Background

Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma.

Methods

This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner.

Results

The detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI.

Conclusions

AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.
Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours
Authors: Ho Karyn S , Poon Peter C , Owen Shawn C , Shoichet Molly S
Published: December 2012

Background

Human tumour xenografts in immune compromised mice are widely used as cancer models because they are easy to reproduce and simple to use in a variety of pre-clinical assessments. Developments in nanomedicine have led to the use of tumour xenografts in testing nanoscale delivery devices, such as nanoparticles and polymer-drug conjugates, for targeting and efficacy via the enhanced permeability and retention (EPR) effect. For these results to be meaningful, the hyperpermeable vasculature and reduced lymphatic drainage associated with tumour pathophysiology must be replicated in the model. In pre-clinical breast cancer xenograft models, cells are commonly introduced via injection either orthotopically (mammary fat pad, MFP) or ectopically (subcutaneous, SC), and the organ environment experienced by the tumour cells has been shown to influence their behaviour.

Methods

To evaluate xenograft models of breast cancer in the context of EPR, both orthotopic MFP and ectopic SC injections of MDA-MB-231-H2N cells were given to NOD scid gamma (NSG) mice. Animals with matched tumours in two size categories were tested by injection of a high molecular weight dextran as a model nanocarrier. Tumours were collected and sectioned to assess dextran accumulation compared to liver tissue as a positive control. To understand the cellular basis of these observations, tumour sections were also immunostained for endothelial cells, basement membranes, pericytes, and lymphatic vessels.

Results

SC tumours required longer development times to become size matched to MFP tumours, and also presented wide size variability and ulcerated skin lesions 6 weeks after cell injection. The 3 week MFP tumour model demonstrated greater dextran accumulation than the size matched 5 week SC tumour model (forP < 0.10). Immunostaining revealed greater vascular density and thinner basement membranes in the MFP tumour model 3 weeks after cell injection. Both the MFP and SC tumours showed evidence of insufficient lymphatic drainage, as many fluid-filled and collagen IV-lined spaces were observed, which likely contain excess interstitial fluid.

Conclusions

Dextran accumulation and immunostaining results suggest that small MFP tumours best replicate the vascular permeability required to observe the EPR effect in vivo. A more predictable growth profile and the absence of ulcerated skin lesions further point to the MFP model as a strong choice for long term treatment studies that initiate after a target tumour size has been reached.
RETRACTED ARTICLE: Observational study:
daily treatment with a new compound “tradamixina” plus serenoa repens for two months
improved the lower urinary tract symptoms
Authors: Iacono Fabrizio , Prezioso Domenico , Illiano Ester , Ruffo Antonio , Romeo Giuseppe , Amato Bruno
Published: December 2012

Background

Lower urinary tract symptoms (LUTS) are associated with great emotional costs
to individuals and substantial economic costs to society. This study seeks to
evaluate the effect of a new natural compound “Tradamixina plus Serenoa Repens” in
order to improve lower urinary tract symptoms.

Methods

100 patients (≥45years) who had had LUTS/BPH for >6 mo at screening and
with IPSS -The international Prostate symptom scores- ≥13 and maximum urinary flow
rate (Qmax) ≥4 to ≤15 ml/s. were recruited. The compound “Tradamixina plus Serenoa
Repens” (80 mg of Alga Ecklonia Bicyclis, 100 mg of Tribulus Terrestris and 100 mg
of D-Glucosamine and N-Acetyl-D-Glucosamine plus 320 mg of Serenoa Repens) was
administered daily for 2 months. At visit and after 60 days of treatment patients
were evaluated by means of detailed medical urological history, clinical
examination, laboratory investigations (total PSA), and instrumental examination
like urolfowmetry. Efficacy measures included IPSS-International Prostate Sympto,
BPH Impact Index (BII), Quality-of-Life (QoL) Index. Measures were assessed at
baseline and end point (12 wk or end of therapy) and also at screening, 1 and 4 wk
for IPSS, and 4 wk for BII. Statistical significance was interpreted only if the
results of the preceding analysis were significant at the 0.05 level.

Results

After 2 months of treatment the change from baseline to week 12 relative to
“Tradamixina plus Seronea Repens” in total IPSS and Qol was statistically
significant. Differences from baseline in BII were statistically significant for
“Tradamixina plus Seronea Repens” above all differences in BII were also
significant at 4 wk (LSmean ± SE: -0.8 ± 0.2). In the distribution of subjects
over the PGI-I and CGI-I response categories were significant for”Tradamixina plus
Seronea Repens” (PGI-I: p = 0.001; CGI-I). We also observed a decrease of total
PSA.

Conclusion

The daily treatment with a new compound “Tradamixina plus Serenoa Repens” for
2 months improved the male sexual function , it improved the bother symptoms which
affect the patient’s quality of life , improved uroflowmetric parameters, and we
also observed a decrease of serum PSA level.