bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibiting Interactions of Lysine Demethylase LSD1 with Snail/Slug Blocks Cancer Cell Invasion
Authors: Ferrari-Amorotti Giovanna , Fragliasso Valentina , Esteki Roza , Prudente Zelia , Soliera Angela Rachele , Cattelani Sara , Manzotti Gloria , Grisendi Giulia , Dominici Massimo , Pieraccioli Marco , Raschellà Giuseppe , Chiodoni Claudia , Colombo Mario Paolo , Calabretta Bruno
Published: October 2012

The process of epithelial–mesenchymal transition (EMT) which is required for cancer cell invasion is regulated by a family of E-box–binding transcription repressors, which include Snail (SNAIL1) and Slug (SNAI2). Snail appears to repress the expression of the EMT marker E-cadherin by epigenetic mechanisms dependent on the interaction of its N-terminal SNAG domain with chromatin-modifying proteins including lysine-specific demethylase 1 (LSD1/KDM1A). We assessed whether blocking Snail/Slug-LSD1 interaction by treatment with Parnate, an enzymatic inhibitor of LSD1, or TAT-SNAG, a cell-permeable peptide corresponding to the SNAG domain of Slug, suppresses the motility and invasiveness of cancer cells of different origin and genetic background. We show here that either treatment blocked Slug-dependent repression of the E-cadherin promoter and inhibited the motility and invasion of tumor cell lines without any effect on their proliferation. These effects correlated with induction of epithelial and repression of mesenchymal markers and were phenocopied by LSD1 or Slug downregulation. Parnate treatment also inhibited bone marrow homing/engraftment of Slug-expressing K562 cells. Together, these studies support the concept that targeting Snail/Slug-dependent transcription repression complexes may lead to the development of novel drugs selectively inhibiting the invasive potential of cancer cells. Cancer Res; 73(1); 235–45. ©2012 AACR.
Impact of Tumor Progression on Cancer Incidence Curves
Authors: Luebeck E. Georg , Curtius Kit , Jeon Jihyoun , Hazelton William D.
Published: October 2012

Cancer arises through a multistage process, but it is not fully clear how this process influences the age-specific incidence curve. Studies of colorectal and pancreatic cancer using the multistage clonal expansion (MSCE) model have identified two phases of the incidence curves. One phase is linear, beginning about age of 60 years, suggesting that at least two rare rate-limiting mutations occur before clonal expansion of premalignant cells. A second phase is exponential, seen in early-onset cancers occurring before the age of 60 years that are associated with premalignant clonal expansion. Here, we extend the MSCE model to include clonal expansion of malignant cells, an advance that permits study of the effects of tumor growth and extinction on the incidence of colorectal, gastric, pancreatic, and esophageal adenocarcinomas in the digestive tract. After adjusting the age-specific incidence for birth-cohort and calendar-year trends, we found that initiating mutations and premalignant cell kinetics can explain the primary features of the incidence curve. However, we also found that the incidence data of these cancers harbored information on the kinetics of malignant clonal expansion before clinical detection, including tumor growth rates and extinction probabilities on three characteristic time scales for tumor progression. In addition, the data harbored information on the mean sojourn times for premalignant clones until occurrence of either the first malignant cell or the first persistent (surviving) malignant clone. Finally, the data also harbored information on the mean sojourn time of persistent malignant clones to the time of diagnosis. In conclusion, cancer incidence curves can harbor significant information about hidden processes of tumor initiation, premalignant clonal expansion, and malignant transformation, and even some limited information on tumor growth before clinical detection. Cancer Res; 73(3); 1086–96. ©2012 AACR.
Epithelial-to-Mesenchymal Transition Induced by TGF-β1 Is Mediated by Blimp-1–Dependent Repression of BMP-5
Authors: Romagnoli Mathilde , Belguise Karine , Yu Ziyang , Wang Xiaobo , Landesman-Bollag Esther , Seldin David C. , Chalbos Dany , Barillé-Nion Sophie , Jézéquel Pascal , Seldin Margaret L. , Sonenshein Gail E.
Published: October 2012

Induction of epithelial-to-mesenchymal transition (EMT) by TGF-β1 requires Ras signaling. We recently identified the transcriptional repressor Blimp-1 (PRDM1) as a downstream effector of the NF-κB, RelB/Bcl-2/Ras-driven pathway that promotes breast cancer cell migration. As the RelB/Blimp-1 pathway similarly required Ras signaling activation, we tested whether Blimp-1 plays a role in TGF-β1–mediated EMT. Here, TGF-β1 treatment of untransformed NMuMG mammary epithelial and MDA-MB-231 breast cancer cells was shown to induce Blimp-1 expression, which promoted an EMT signature and cell migration. TGFB1 and BLIMP1 RNA levels were correlated in patient breast tumors. BLIMP1 gene transcription was activated by TGF-β1 via a c-Raf (RAF1) to AP-1 pathway. Blimp-1 induced expression of the EMT master regulator Snail (SNAI1) via repressing BMP-5, which inhibited Snail expression upon TGF-β1 treatment. Interestingly, a similar cascade was observed during postnatal mouse mammary gland development. RelB expression was detected early in pregnancy followed progressively by Blimp-1 and then Snail; whereas, BMP-5 levels were high in nulliparous and regressing glands. Finally, lower BMP5 RNA levels were detected in patient breast tumors versus normal tissues, and correlated with cancer recurrence. Thus, the Ras effector Blimp-1 plays an essential role in TGF-β1–induced EMT via repression of BMP-5 in breast cancer. Cancer Res; 72(23); 6268–78. ©2012 AACR.
Plasma factor Xa inhibition can predict antithrombotic effects of oral direct factor Xa inhibitors in rabbit atherothrombosis models
Authors: Yamashita Atsushi , Kaku Seiji , Iwatsuki Yoshiyuki , Asada Yujiro , Funatsu Toshiyuki
Published: October 2012

We evaluated the relationship between antithrombotic effects and pharmacodynamic (PD) marker changes produced by the novel factor (F)Xa inhibitors darexaban (YM150) and rivaroxaban in a rabbit model of plaque disruption-induced arterial thrombosis. Animals were subjected to catheter-induced endothelial denudation via the femoral artery followed by a two-week high-cholesterol diet. Plaque disruption was induced by balloon angioplasty, and then stasis was achieved by ligation at the distal side of the injured segment. Darexaban and rivaroxaban were administered orally 1 hour (h) before and 9 h after plaque disruption, and their antithrombotic effects were evaluated 24 h after the initiation of ligation. Prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma FXa activity were measured using blood samples collected before and 1 h after administration. Darexaban and rivaroxaban significantly reduced thrombus formation. The thrombus weight obtained in the 30 mg/kg darexaban group was comparable to that in the 1 mg/kg rivaroxaban group (2.17 ± 0.63 and 3.23 ± 1.64 mg, respectively, vs. 8.01 ± 1.08 mg in the control group). Plasma FXa activity correlated with the antithrombotic effects of darexaban and rivaroxaban, while PT only correlated with those of darexaban. Our findings suggest that the degree of plasma FXa inhibition may be useful for predicting antithrombotic effects of darexaban and rivaroxaban in arterial thrombosis. PT may also be useful in evaluating antithrombotic effects of darexaban in particular.
The Retrieval of Profiles of Particulate Extinction from Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) Data: Uncertainty and Error Sensitivity Analyses
Authors: Young Stuart A. , Vaughan Mark A. , Kuehn Ralph E. , Winker David M.
Published: October 2012

Profiles of atmospheric cloud and aerosol extinction coefficients are retrieved on a global scale from measurements made by the lidar on board the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) mission since mid-June 2006. This paper presents an analysis of how the uncertainties in the inputs to the extinction retrieval algorithm propagate as the retrieval proceeds downward to lower levels of the atmosphere. The mathematical analyses, which are being used to calculate the uncertainties reported in the current (version 3) data release, are supported by figures illustrating the retrieval uncertainties in both simulated and actual data. Equations are also derived that describe the sensitivity of the extinction retrieval algorithm to errors in profile calibration and in the lidar ratios used in the retrievals. Biases that could potentially result from low signal-to-noise ratios in the data are also examined. Using simulated data, the propagation of bias errors resulting from errors in profile calibration and lidar ratios is illustrated.
Data Assimilation with Gaussian Mixture Models Using the Dynamically Orthogonal Field Equations. Part I: Theory and Scheme
Authors: Sondergaard Thomas , Lermusiaux Pierre F. J.
Published: October 2012

This work introduces and derives an efficient, data-driven assimilation scheme, focused on a time-dependent stochastic subspace that respects nonlinear dynamics and captures non-Gaussian statistics as it occurs. The motivation is to obtain a filter that is applicable to realistic geophysical applications, but that also rigorously utilizes the governing dynamical equations with information theory and learning theory for efficient Bayesian data assimilation. Building on the foundations of classical filters, the underlying theory and algorithmic implementation of the new filter are developed and derived. The stochastic Dynamically Orthogonal (DO) field equations and their adaptive stochastic subspace are employed to predict prior probabilities for the full dynamical state, effectively approximating the Fokker–Planck equation. At assimilation times, the DO realizations are fit to semiparametric Gaussian Mixture Models (GMMs) using the Expectation-Maximization algorithm and the Bayesian Information Criterion. Bayes’s law is then efficiently carried out analytically within the evolving stochastic subspace. The resulting GMM-DO filter is illustrated in a very simple example. Variations of the GMM-DO filter are also provided along with comparisons with related schemes.
Data Assimilation with Gaussian Mixture Models Using the Dynamically Orthogonal Field Equations. Part II: Applications
Authors: Sondergaard Thomas , Lermusiaux Pierre F. J.
Published: October 2012

The properties and capabilities of the Gaussian Mixture Model–Dynamically Orthogonal filter (GMM-DO) are assessed and exemplified by applications to two dynamical systems: 1) the double well diffusion and 2) sudden expansion flows; both of which admit far-from-Gaussian statistics. The former test case, or twin experiment, validates the use of the Expectation-Maximization (EM) algorithm and Bayesian Information Criterion with GMMs in a filtering context; the latter further exemplifies its ability to efficiently handle state vectors of nontrivial dimensionality and dynamics with jets and eddies. For each test case, qualitative and quantitative comparisons are made with contemporary filters. The sensitivity to input parameters is illustrated and discussed. Properties of the filter are examined and its estimates are described, including the equation-based and adaptive prediction of the probability densities; the evolution of the mean field, stochastic subspace modes, and stochastic coefficients; the fitting of GMMs; and the efficient and analytical Bayesian updates at assimilation times and the corresponding data impacts. The advantages of respecting nonlinear dynamics and preserving non-Gaussian statistics are brought to light. For realistic test cases admitting complex distributions and with sparse or noisy measurements, the GMM-DO filter is shown to fundamentally improve the filtering skill, outperforming simpler schemes invoking the Gaussian parametric distribution.
Perceptions of Racialized Opportunities and Hispanics’ Political Attitudes
Authors: Samson Frank L.
Published: October 2012

In an attempt to understand Hispanics’ political incorporation as the United States becomes a “majority-minority” nation, I explore some of the social-psychological processes that shape Hispanics’ political attitudes. Specifically, I draw on the segmented-assimilation literature’s notion of “modes of incorporation” to argue that immigrants develop perceptions of racialized opportunities (PROPs) as they confront America’s segmented opportunity structure. Because of the durability of these racialized mobility trajectories, I propose that PROPs play an important part in the formation of Hispanics’ political attitudes. I test the PROPs mechanism using the 2006 Latino National Survey with a sample of 8,634 Hispanic respondents. Ordinal logistic regression models, estimating Hispanics’ support for school vouchers and government intervention in health care, indicate that PROPs are related to Hispanics’ political attitudes, especially in regard to support for school vouchers. Moreover, this social-psychological mechanism informs the political attitudes of both U.S.-born and foreign-born Hispanics.
Is Ethnicity Identifiable?
Authors: Harris Adam S. , Findley Michael G.
Published: October 2012

Ethnicity is frequently posited as an important factor in civil violence and other political contexts. Despite the attention that ethnicity receives, its effects depend on an important, but mostly ignored, assumption that ethnicity is identifiable within and across groups. There is likely considerable variation in peoples’ abilities to identify each other. Certain individuals within groups might be better at identifying others’ ethnicities; further, different types of information might aid identification better. We contend that the strength of an individual’s ethnic identity influences her ability to identify others correctly. We test this argument using an experiment in the Eastern Cape of South Africa in which individuals attempted to identify members of the major black ethnic groups. We find that the average individual struggles to identify ethnicity correctly in many conditions. Individuals with a stronger identity, however, are often better at correctly identifying the ethnicity of others relative to the average individual. When receiving contradictory information, individuals with stronger identities were sometimes deceived more easily than others. These results have implications for a diverse set of studies relying on the identifiability assumption.
The Women’s Movement in India: A Hundred Year History
Authors: Krishnaraj Maithreyi
Published: October 2012

The women’s movement in India goes back to more than a hundred years but its composition, its agenda, its form and style, its outreach, its inclusiveness have been changing over the years. The social reform movement before independence first addressed the woman’s condition within Hindu society but this was restricted to the women in the upper castes and exposed illiberal traditions such as that of treatment of widows and child marriage and was largely sponsored by men who saw threats to Hindu society by colonial powers’ criticisms and hence wished to safeguard their cultural edifices by reforming what they thought were mere aberrations but left the patriarchal social structure un touched. Subsequent events were induction of women in the nationalist movement, the Constitution’s promise of gender equality; 1974’s Towards Equality Report prepared by the Committee on the Status of Women; international women’s movements and The Convention on the Abolition of all Forms of Discrimination Against Women (CEDAW). Have these instruments been successful in liberating Indian women from patriarchy?
Computerized Adaptive Testing Using a Class of High-Order Item Response Theory Models
Authors: Huang Hung-Yu , Chen Po-Hsi , Wang Wen-Chung
Published: October 2012

In the human sciences, a common assumption is that latent traits have a hierarchical structure. Higher order item response theory models have been developed to account for this hierarchy. In this study, computerized adaptive testing (CAT) algorithms based on these kinds of models were implemented, and their performance under a variety of situations was examined using simulations. The results showed that the CAT algorithms were very effective. The progressive method for item selection, the Sympson and Hetter method with online and freeze procedure for item exposure control, and the multinomial model for content balancing can simultaneously maintain good measurement precision, item exposure control, content balance, test security, and pool usage.
Cortical response to somatosensory stimulation in medication overuse headache patients is influenced by angiotensin converting enzyme (ACE) I/D genetic polymorphism
Authors: Lorenzo Cherubino Di , Coppola Gianluca , Currà Antonio , Grieco Gaetano , Santorelli Filippo M , Lepre Chiara , Porretta Elisa , Pascale Esterina , Pierelli Francesco
Published: October 2012

Background

Medication overuse headache (MOH) is a disabling health problem. Convincing evidence attributes a pathophysiologic role to central sensitization. By recording somatosensory evoked potentials (SSEPs) in patients with MOH, we observed increased sensitization and deficient habituation to repetitive sensory stimuli consistent with drug overuse. The renin–angiotensin system in the brain seems to play a relevant role in neural plasticity and dependence behavior. We therefore sought differences in SSEP sensitization and habituation in patients with MOH who underwent angiotensin converting enzyme (ACE) I/D polymorphism analysis.

Methods

We recorded median-nerve SSEPs (two blocks of 100 sweeps) in 43 patients with MOH. We measured N20–P25 amplitudes, and assessed sensitization using the first block amplitudes, and habituation using amplitude changes between the two sequential blocks. According to their genotype, subjects were divided into three groups: “D/D”, “D/I” and “I/I” carriers.

Results

The habituation slope of the two SSEP block amplitudes was significantly increased in the D/D subgroup ( n = 16) with respect to that of the I/I subgroup ( n = 6), with the D/I subgroup ( n = 21) falling in between. In D/D carriers, the habituation slope correlated positively with the duration of the overuse headache, and the first SSEP block amplitudes, a measure of sensitization, increased in strict relationship with the type of overused medication in the MOH patients overall and in the D/D subgroup; this was not so in the D/I and I/I subgroups.

Conclusion

In patients with MOH, the homozygote D/D ACE polymorphism influences habituation and sensitization to repeated sensory stimuli in strict relationship with medication overuse. We suggest that angiotensin peptides influence neuronal mechanisms of plasticity by interacting with central monoaminergic synaptic transmission.
Detection of Avian coronavirus infectious bronchitis virus type QX infection in Switzerland
Authors: Sigrist Brigitte , Tobler Kurt , Schybli Martina , Konrad Leonie , Stöckli René , Cattoli Giovanni , Lüschow Dörte , Hafez Hafez M. , Britton Paul , Hoop Richard K. , Vögtlin Andrea
Published: October 2012

Infectious bronchitis, a disease of chickens caused by Avian coronavirus infectious bronchitis virus (IBV), leads to severe economic losses for the poultry industry worldwide. Various attempts to control the virus based on vaccination strategies are performed. However, due to the emergence of novel genotypes, an effective control of the virus is hindered. In 1996, a novel viral genotype named IBV-QX was reported for the first time in Qingdao, Shandong province, China. The first appearance of an IBV-QX isolate in Europe was reported between 2003 and 2004 in The Netherlands. Subsequently, infections with this genotype were found in several other European countries such as France, Italy, Germany, United Kingdom, Slovenia, and Sweden. The present report describes the use of a new set of degenerate primers that amplify a 636-bp fragment within the S1 gene by reverse transcription polymerase chain reaction to detect the occurrence of IBV-QX infection in Switzerland.
Toward a Model of Scientists’ Public Communication Activity
Authors: Dudo Anthony
Published: October 2012

This study aims to contribute to our empirical understanding of the factors and processes that lead scientists to engage in public communication. Using a national sample, this study identifies key factors that contribute to scientists’ public communication activity, including a scientist’s status, communication autonomy, use of print and online media, intrinsic rewards, communication training, perceived behavioral controls, normative beliefs, and perceived level of medialization. In addition to these findings, this study aims to extend our understanding of the popularization process by injecting theoretical rationale, accounting for indirect pathways of influence, and proposing a baseline model that can be refined over time.
HCV glycoprotein E2 is a novel BDCA-2 ligand and acts as an inhibitor of IFN production by plasmacytoid dendritic cells
Authors: Florentin Jonathan , Aouar Besma , Dental Clélia , Thumann Christine , Firaguay Guylène , Gondois-Rey Francoise , Soumelis Vassili , Baumert Thomas F. , Nunès Jacques A. , Olive Daniel , Hirsch Ivan , Stranska Ruzena
Published: October 2012

The elimination of hepatitis C virus (HCV) in > 50% of chronically infected patients by treatment with IFN-α suggests that plasmacytoid dendritic cells (pDCs), major producers of IFN-α, play an important role in the control of HCV infection. However, despite large amounts of Toll-like receptor 7-mediated IFN-α, produced by pDCs exposed to HCV-infected hepatocytes, HCV still replicates in infected liver. Here we show that HCV envelope glycoprotein E2 is a novel ligand of pDC C-type lectin immunoreceptors (CLRs), blood DC antigen 2 (BDCA-2) and DC-immunoreceptor (DCIR). HCV particles inhibit, via binding of E2 glycoprotein to CLRs, production of IFN-α and IFN-λ in pDCs exposed to HCV-infected hepatocytes, and induce in pDCs a rapid phosphorylation of Akt and Erk1/2, in a manner similar to the crosslinking of BDCA-2 or DCIR. Blocking of BDCA-2 and DCIR with Fab fragments of monoclonal antibodies preserves the capacity of pDCs to produce type I and III IFNs in the presence of HCV particles. Thus, negative interference of CLR signaling triggered by cell-free HCV particles with Toll-like receptor signaling triggered by cell-associated HCV results in the inhibition of the principal pDC function, production of IFN.
A detailed proteomic analysis of rhodocytin-activated platelets reveals novel clues on the CLEC-2 signalosome: implications for CLEC-2 signaling regulation
Authors: Parguiña Andrés F. , Alonso Jana , Rosa Isaac , Vélez Paula , González-López María J. , Guitián Esteban , Eble Johannes A. , Loza María I. , García Ángel
Published: October 2012

C-type lectin-like receptor 2 (CLEC-2) is an essential platelet-activating receptor in hemostasis and thrombosis that is activated by the snake venom rhodocytin. We present here a differential proteomic analysis of basal and rhodocytin-activated platelets with the aim of providing novel clues on CLEC-2 signaling regulation. Proteome analysis was based on 2D-DIGE, phosphotyrosine immunoprecipitations followed by 1D SDS-PAGE and mass spectrometry. Protein-protein interactions were studied by coimmunoprecipitations and a systems biology approach. Overall, we identified 132 proteins differentially regulated after CLEC-2 platelet activation, including most of the major players reported so far in the signaling cascade. In addition, we identified various proteins not previously known to participate in CLEC-2 signaling, such as the adapters Dok-2 and ADAP, tyrosine kinase Fer, and tyrosine phosphatase SHIP-1. We also report an increased association between Dok-2 and SHIP-1 in rhodocytin-stimulated platelets, which might negatively regulate CLEC-2 signaling. Moreover, we also present a comparative analysis of proteomic data for CLEC-2 and glycoprotein VI signaling. We think that our data provide thrombosis-relevant information on CLEC-2 signaling regulation, contributing to a better understanding of this important signaling cascade.
Genome of Epinotia aporema granulovirus (EpapGV), a polyorganotropic fast killing betabaculovirus with a novel thymidylate kinase gene
Authors: Ferrelli María Leticia , Salvador Ricardo , Biedma Marina Elizabeth , Berretta Marcelo Facundo , Haase Santiago , Sciocco-Cap Alicia , Ghiringhelli Pablo Daniel , Romanowski Víctor
Published: October 2012

Background

Epinotia aporema (Lepidoptera: Tortricidae) is an important pest of legume crops in South America. Epinotia aporema granulovirus (EpapGV) is a baculovirus that causes a polyorganotropic infection in the host larva. Its high pathogenicity and host specificity make EpapGV an excellent candidate to be used as a biological control agent.

Results

The genome of Epinotia aporema granulovirus (EpapGV) was sequenced and analyzed. Its circular double-stranded DNA genome is 119,082 bp in length and codes for 133 putative genes. It contains the 31 baculovirus core genes and a set of 19 genes that are GV exclusive. Seventeen ORFs were unique to EpapGV in comparison with other baculoviruses. Of these, 16 found no homologues in GenBank, and one encoded a thymidylate kinase. Analysis of nucleotide sequence repeats revealed the presence of 16 homologous regions (hrs) interspersed throughout the genome. Each hr was characterized by the presence of 1 to 3 clustered imperfect palindromes which are similar to previously described palindromes of tortricid-specific GVs. Also, one of the hrs (hr4) has flanking sequences suggestive of a putative non-hr ori. Interestingly, two more complex hrs were found in opposite loci, dividing the circular dsDNA genome in two halves. Gene synteny maps showed the great colinearity of sequenced GVs, being EpapGV the most dissimilar as it has a 20 kb-long gene block inversion. Phylogenetic study performed with 31 core genes of 58 baculoviral genomes suggests that EpapGV is the baculovirus isolate closest to the putative common ancestor of tortricid specific betabaculoviruses.

Conclusions

This study, along with previous characterization of EpapGV infection, is useful for the better understanding of the pathology caused by this virus and its potential utilization as a bioinsecticide.
Effect of environmental stress factors on the uptake and survival of Campylobacter jejuni in Acanthamoeba castellanii
Authors: Bui Xuan Thanh , Qvortrup Klaus , Wolff Anders , Bang Dang Duong , Creuzenet Carole
Published: October 2012

Background

Campylobacter jejuni is a major cause of bacterial food-borne illness in Europe and North America. The mechanisms allowing survival in the environment and transmission to new hosts are not well understood. Environmental free-living protozoa may facilitate both processes. Pre-exposure to heat, starvation, oxidative or osmotic stresses encountered in the environment may affect the subsequent interaction of C. jejuni with free-living protozoa. To test this hypothesis, we examined the impact of environmental stress on expression of virulence-associated genes (ciaB, dnaJ, and htrA) of C. jejuni and on its uptake by and intracellular survival within Acanthamoeba castellanii.

Results

Heat, starvation and osmotic stress reduced the survival of C. jejuni significantly, whereas oxidative stress had no effect. Quantitative RT-PCR experiments showed that the transcription of virulence genes was slightly up-regulated under heat and oxidative stresses but down-regulated under starvation and osmotic stresses, the htrA gene showing the largest down-regulation in response to osmotic stress. Pre-exposure of bacteria to low nutrient or osmotic stress reduced bacterial uptake by amoeba, but no effect of heat or oxidative stress was observed. Finally, C. jejuni rapidly lost viability within amoeba cells and pre-exposure to oxidative stress had no significant effect on intracellular survival. However, the numbers of intracellular bacteria recovered 5 h post-gentamicin treatment were lower with starved, heat treated or osmotically stressed bacteria than with control bacteria. Also, while ~1.5 × 103 colony forming unit/ml internalized bacteria could typically be recovered 24 h post-gentamicin treatment with control bacteria, no starved, heat treated or osmotically stressed bacteria could be recovered at this time point. Overall, pre-exposure of C. jejuni to environmental stresses did not promote intracellular survival in A. castellanii.

Conclusions

Together, these findings suggest that the stress response in C. jejuni and its interaction with A. castellanii are complex and multifactorial, but that pre-exposure to various stresses does not prime C. jejuni for survival within A. castellanii.
Endoscopically observable white nodule caused by distal intramural lymphatic spread of rectal cancer: a case report
Authors: Tsumura Ayako , Yokoyama Shozo , Takifuji Katsunari , Hotta Tsukasa , Matsuda Kenji , Watanabe Takashi , Mitani Yasuyuki , Yamaue Hiroki
Published: October 2012

This report describes a case of rectal cancer with endoscopically observable white nodules caused by distal intramural lymphatic spread. A 57-year-old female presented to our hospital with frequent diarrhea and hemorrhoids. Computed tomography showed bilateral ovarian masses and three hepatic tumors diagnosed as rectal cancer metastases, and also showed multiple lymph node involvement. The patient was preoperatively diagnosed with stage IV rectal cancer. Colonoscopy demonstrated that primary rectal cancer existed 15 cm from the anal verge and that there were multiple white small nodules on the anal side of the primary tumor extending to the dentate line. Biopsies of the white spots were performed, and they were identified as adenocarcinoma. The patient underwent Hartmann’s procedure because of the locally advanced primary tumor. The white nodules were ultimately diagnosed as being caused by intramural lymphatic spreading because lymphatic permeation was strongly positive at the surrounding area. Small white nodules near a primary rectal cancer should be suspected of being intramural spreading. Endoscopic detection of white nodules may be useful for the diagnosis of distal intramural spread.
Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas
Authors: Wang Zhaohui , Li Lili , Su Xianwei , Gao Zifen , Srivastava Gopesh , Murray Paul G , Ambinder Richard , Tao Qian
Published: October 2012

Background

Inactivaion of tumor suppressor genes (TSGs) by promoter CpG methylation frequently occurs in tumorigenesis, even in the early stages, contributing to the initiation and progression of human cancers. Deleted in lung and esophageal cancer 1 (DLEC1), located at the 3p22-21.3 TSG cluster, has been identified frequently silenced by promoter CpG methylation in multiple carcinomas, however, no study has been performed for lymphomas yet.

Methods

We examined the expression of DLEC1 by semi-quantitative reverse transcription (RT)-PCR, and evaluated the promoter methylation of DLEC1 by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) in common lymphoma cell lines and tumors.

Results

Here we report that DLEC1 is readily expressed in normal lymphoid tissues including lymph nodes and PBMCs, but reduced or silenced in 70% (16/23) of non-Hodgkin and Hodgkin lymphoma cell lines, including 2/6 diffuse large B-cell (DLBCL), 1/2 peripheral T cell lymphomas, 5/5 Burkitt, 6/7 Hodgkin and 2/3 nasal killer (NK)/T-cell lymphoma cell lines. Promoter CpG methylation was frequently detected in 80% (20/25) of lymphoma cell lines and correlated with DLEC1 downregulation/silencing. Pharmacologic demethylation reversed DLEC1 expression in lymphoma cell lines along with concomitant promoter demethylation. DLEC1 methylation was also frequently detected in 32 out of 58 (55%) different types of lymphoma tissues, but not in normal lymph nodes. Furthermore, DLEC1 was specifically methylated in the sera of 3/13 (23%) Hodgkin lymphoma patients.

Conclusions

Thus, methylation-mediated silencing of DLEC1 plays an important role in multiple lymphomagenesis, and may serve as a non-invasive tumor marker for lymphoma diagnosis.
Full genomic analysis of an influenza A (H1N2) virus identified during 2009 pandemic in Eastern India: evidence of reassortment event between co-circulating A(H1N1)pdm09 and A/Brisbane/10/2007-like H3N2 strains
Authors: Mukherjee Tapasi Roy , Agrawal Anurodh S , Chakrabarti Sekhar , Chawla-Sarkar Mamta
Published: October 2012

Background

During the pandemic [Influenza A(H1N1)pdm09] period in 2009-2010, an influenza A (Inf-A) virus with H1N2 subtype (designated as A/Eastern India/N-1289/2009) was detected from a 25 years old male from Mizoram (North-eastern India).

Objective

To characterize full genome of the H1N2 influenza virus.

Methods

For initial detection of Influenza viruses, amplification of matrix protein (M) gene of Inf-A and B viruses was carried out by real time RT-PCR. Influenza A positive viruses are then further subtyped with HA and NA gene specific primers. Sequencing and the phylogenetic analysis was performed for the H1N2 strain to understand its origin.

Results

The outcome of this full genome study revealed a unique reassortment event where the N-1289 virus acquired it’s HA gene from a 2009 pandemic H1N1 virus with swine origin and the other genes from H3N2-like viruses of human origin.

Conclusions

This study provides information on possibility of occurrence of reassortment events during influenza season when infectivity is high and two different subtypes of Inf-A viruses co-circulate in same geographical location.
Analysis of the humoral immune responses among cynomolgus macaque naturally infected with Reston virus during the 1996 outbreak in the Philippines
Authors: Taniguchi Satoshi , Sayama Yusuke , Nagata Noriyo , Ikegami Tetsuro , Miranda Mary E , Watanabe Shumpei , Iizuka Itoe , Fukushi Shuetsu , Mizutani Tetsuya , Ishii Yoshiyuki , Saijo Masayuki , Akashi Hiroomi , Yoshikawa Yasuhiro , Kyuwa Shigeru , Morikawa Shigeru
Published: October 2012

Background

Ebolaviruses induce lethal viral hemorrhagic fevers (VHFs) in humans and non-human primates, with the exceptions of Reston virus (RESTV), which is not pathogenic for humans. In human VHF cases, extensive analyses of the humoral immune responses in survivors and non-survivors have shown that the IgG responses to nucleoprotein (NP) and other viral proteins are associated with asymptomatic and survival outcomes, and that the neutralizing antibody responses targeting ebolaviruses glycoprotein (GP1,2) are the major indicator of protective immunity. On the other hand, the immune responses in non-human primates, especially naturally infected ones, have not yet been elucidated in detail, and the significance of the antibody responses against NP and GP1,2 in RESTV-infected cynomolgus macaques is still unclear. In this study, we analyzed the humoral immune responses of cynomolgus macaque by using serum specimens obtained from the RESTV epizootic in 1996 in the Philippines to expand our knowledge on the immune responses in naturally RESTV-infected non-human primates.

Results

The antibody responses were analyzed using IgG-ELISA, an indirect immunofluorescent antibody assay (IFA), and a pseudotyped VSV-based neutralizing (NT) assay. Antigen-capture (Ag)-ELISA was also performed to detect viral antigens in the serum specimens. We found that the anti-GP1,2 responses, but not the anti-NP responses, closely were correlated with the neutralization responses, as well as the clearance of viremia in the sera of the RESTV-infected cynomolgus macaques. Additionally, by analyzing the cytokine/chemokine concentrations of these serum specimens, we found high concentrations of proinflammatory cytokines/chemokines, such as IFNγ, IL8, IL-12, and MIP1α, in the convalescent phase sera.

Conclusions

These results imply that both the antibody response to GP1,2 and the proinflammatory innate responses play significant roles in the recovery from RESTV infection in cynomolgus macaques.
An overview of the contribution of fatness and fitness factors, and the role of exercise, in the formation of health status for individuals who are overweight
Authors: Clark James E
Published: October 2012

Over the last half century there has been an epidemic of diminished health status induced by what seems as a concurrent rise in a population of individuals that are overfat. During the past few decades, the use of exercise has become a staple in the prevention and treatment options for the retarding the development of health issues pertaining to individuals who are overweight, overfatness or experience obesity. However, there are few studies and reviews look at the global issues surrounding the metabolic and hormone consequences of overfatness and the interaction of exercise with adiposity in humans developing the health status for the individual. This review offers an insight into our current understanding of health issues pertaining to metabolic and hormonal disruption related to overfatness and the treatment effect that exercise, especially resistance exercise, can have on impacting the health status, and overall well-being, for individuals who are overfat, regardless of body compositional changes leading toward a lessening of diseased state, and eventually a return to a normal health status for the individual.
Pregnancy Ambivalence and Contraceptive Use Among Young Adults in the United States
Authors: Higgins Jenny A. , Popkin Ronna A. , Santelli John S.
Published: October 2012

CONTEXT

Pregnancy ambivalence, or conflicted desire about having a baby, has been associated with decreased contraceptive use and unintended pregnancy. However, prior studies have neither included men nor focused on young adults, even though people in their 20s have the highest rates of unintended pregnancy.

METHODS

Nationally representative data from 2008–2009 were used to examine pregnancy ambivalence and its association with contraceptive practices among 774 respondents who were 18–29 years old and in current sexual relationships. Bivariate and multivariate analyses assessed relationships between pregnancy ambivalence, contraceptive use, gender and other social, demographic and psychosocial variables.

RESULTS

Forty‐five percent of respondents exhibited pregnancy ambivalence. The proportion was higher among men than among women (53% vs. 36%), and the difference remained significant in the multivariate analysis (odds ratio, 2.9). Ambivalence was associated with lowered likelihood of contraceptive use, but this relationship was statistically significant only for men: Compared with men with clear intentions to avoid pregnancy, ambivalent men were less likely to have used any method of contraception in the last month (0.4).

CONCLUSIONS

The association between men's pregnancy ambivalence and contraceptive practices suggests that women should not remain the sole targets of pregnancy prevention programs. Further research should explore whether clinical interventions that assess and address pregnancy ambivalence for both women and men could lead to improved contraceptive counseling and use.
Development of PCL-PEG nanofibrous mats as alternative carriers for recombinant Chinese hamster ovary cells
Authors: Shakibaie Mehdi , Rahbar Marieh Ghafari , Tabandeh Fatemeh , Tavanai Hossein , Zomorodipour Alireza , Ebrahimi Sirous , Morshed Mohammad , Ataie Fariba
Published: October 2012

In this study, six polyblended nanofiber mats, composed of poly ε-caprolactone (PCL)-polyethylene glycol (PEG) mixed at different proportions in an electrospinning solution were fabricated, and then utilized alongside commercial polyester microcarriers for the mass cultivation of recombinant Chinese hamster ovary (rCHO) cells. The SEM micrographs showed that the rCHO cells were attached to the nanofiber mats with significant differences in their affinities, which can be related to the chemical structure and hydrophilicity of the nanofiber mats. The cell densities of the rCHO cells grown on the polyblended PCL-PEG nanofiber mat (80:20)14% were much higher when compared with the commercial polyester microcarrier. Moreover, recombinant protein production increased by approximately 20% when cells were grown on the PCL-PEG nanofiber mat (80:20)14%. The results of this research indicated a potential for the replacement of the commercial polyester microcarrier with the PCL-PEG polyblended nanofiber mats, in order to achieve mass cultivation of recombinant animal cells in industrial bioreactors.
Computational Intelligence: Muster ihrer Entstehung
Authors: Kiendl Harro
Published: October 2012

Dieser Beitrag beschreibt die Geschichte der Computational Intelligence von ihren ersten Anfängen bis zu Künstlichen Neuronalen Netzen, über Evolutionäre Algorithmen bis hin zu Fuzzysystemen. Diese Geschichte ist von vielen Kontroversen geprägt und führt zu offenen Fragen. Einige davon werden hier diskutiert.
CloudMap: A Cloud-Based Pipeline for Analysis of Mutant Genome Sequences
Authors: Minevich Gregory , Park Danny S , Blankenberg Daniel , Poole Richard J , Hobert Oliver
Published: October 2012

Whole genome sequencing (WGS) allows researchers to pinpoint genetic differences between individuals and significantly shortcuts the costly and time-consuming part of forward genetic analysis in model organism systems. Currently, the most effort-intensive part of WGS is the bioinformatic analysis of the relatively short reads generated by second generation sequencing platforms. We describe here a novel, easily accessible and cloud-based pipeline, called CloudMap, which greatly simplifies the analysis of mutant genome sequences. Available on the Galaxy web platform, CloudMap requires no software installation when run on the cloud, but it can also be run locally or via Amazon's Elastic Compute Cloud (EC2) service. CloudMap uses a series of predefined workflows to pinpoint sequence variations in animal genomes, such as those of premutagenized and mutagenized Caenorhabditis elegans strains. In combination with a variant-based mapping procedure, CloudMap allows users to sharply define genetic map intervals graphically and to retrieve very short lists of candidate variants with a few simple clicks. Automated workflows and extensive video user guides are available to detail the individual analysis steps performed (http://usegalaxy.org/cloudmap). We demonstrate the utility of CloudMap for WGS analysis of C. elegans and Arabidopsis genomes and describe how other organisms (e.g., Zebrafish and Drosophila) can easily be accommodated by this software platform. To accommodate rapid analysis of many mutants from large-scale genetic screens, CloudMap contains an in silico complementation testing tool that allows users to rapidly identify instances where multiple alleles of the same gene are present in the mutant collection. Lastly, we describe the application of a novel mapping/WGS method (“Variant Discovery Mapping”) that does not rely on a defined polymorphic mapping strain, and we integrate the application of this method into CloudMap. CloudMap tools and documentation are continually updated at http://usegalaxy.org/cloudmap.
Genomic Tests of Variation in Inbreeding Among Individuals and Among Chromosomes
Authors: Schraiber Joshua G , Shih Stephannie , Slatkin Montgomery
Published: October 2012

We examine the distribution of heterozygous sites in nine European and nine Yoruban individuals whose genomic sequences were made publicly available by Complete Genomics. We show that it is possible to obtain detailed information about inbreeding when a relatively small set of whole-genome sequences is available. Rather than focus on testing for deviations from Hardy–Weinberg genotype frequencies at each site, we analyze the entire distribution of heterozygotes conditioned on the number of copies of the derived (non-chimpanzee) allele. Using Levene’s exact test, we reject Hardy–Weinberg in both populations. We generalized Levene’s distribution to obtain the exact distribution of the number of heterozygous individuals given that every individual has the same inbreeding coefficient, F. We estimated F to be 0.0026 in Europeans and 0.0005 in Yorubans, but we could also reject the hypothesis that F was the same in each individual. We used a composite-likelihood method to estimate F in each individual and within each chromosome. Variation in F across chromosomes within individuals was too large to be consistent with sampling effects alone. Furthermore, estimates of F for each chromosome in different populations were not correlated. Our results show how detailed comparisons of population genomic data can be made to theoretical predictions. The application of methods to the Complete Genomics data set shows that the extent of apparent inbreeding varies across chromosomes and across individuals, and estimates of inbreeding coefficients are subject to unexpected levels of variation, which might be partly accounted for by selection.
Validation of a Short Measure of Effort‐Reward Imbalance in the Workplace: Evidence from China
Authors: Li Jian , Loerbroks Adrian , Shang Li , Wege Natalia , Wahrendorf Morten , Siegrist Johannes
Published: October 2012

Validation of a Short Measure of Effort‐Reward Imbalance in the Workplace: Evidence from China: Jian LI, et al. Mannheim Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, Heidelberg University, Germany—

Objectives

Work stress is an emergent risk in occupational health in China, and its measurement is still a critical issue. The aim of this study was to examine the reliability and validity of a short version of the effort‐reward imbalance (ERI) questionnaire in a sample of Chinese workers.

Methods

A community‐based survey was conducted in 1,916 subjects aged 30−65 years with paid employment (971 men and 945 women).

Results

Acceptable internal consistencies of the three scales, effort, reward and overcommitment, were obtained. Confirmatory factor analysis showed a good model fit of the data with the theoretical structure (goodness‐of‐fit index=0.95). Evidence of criterion validity was demonstrated, as all three scales were independently associated with elevated odds ratios of both poor physical and mental health.

Conclusions

Based on the findings of our study, this short version of the ERI questionnaire is considered to be a reliable and valid tool for measuring psychosocial work environment in Chinese working populations.