bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD1d, a Sentinel Molecule Bridging Innate and Adaptive Immunity, Is Downregulated by the Human Papillomavirus (HPV) E5 Protein: a Possible Mechanism for Immune Evasion by HPV
Authors: Miura Shiho , Kawana Kei , Schust Danny J. , Fujii Tomoyuki , Yokoyama Terufumi , Iwasawa Yuki , Nagamatsu Takeshi , Adachi Katsuyuki , Tomio Ayako , Tomio Kensuke , Kojima Satoko , Yasugi Toshiharu , Kozuma Shiro , Taketani Yuji 
Published: September 2010

ABSTRACTCD1d and CD1d-restricted natural killer T (NKT) cells serve as a natural bridge between innate and adaptive immune responses to microbes. CD1d downregulation is utilized by a variety of microbes to evade immune detection. We demonstrate here that CD1d is downregulated in human papillomavirus (HPV)-positive cellsin vivoandin vitro. CD1d immunoreactivity was strong in HPV-negative normal cervical epithelium but absent in HPV16-positive CIN1 and HPV6-positive condyloma lesions. We used two cell lines forin vitroassay; one was stably CD1d-transfected cells established from an HPV-negative cervical cancer cell line, C33A (C33A/CD1d), and the other was normal human vaginal keratinocyte bearing endogenous CD1d (Vag). Flow cytometry revealed that cell surface CD1d was downregulated in both C33A/CD1d and Vag cells stably transfected with HPV6 E5 and HPV16 E5. Although the steady-state levels of CD1d protein decreased in both E5-expressing cell lines compared to empty retrovirus-infected cells, CD1d mRNA levels were not affected. Confocal microscopy demonstrated that residual CD1d was not trafficked to the E5-expressing cell surface but colocalized with E5 near the endoplasmic reticulum (ER). In the ER, E5 interacted with calnexin, an ER chaperone known to mediate folding of CD1d. CD1d protein levels were rescued by the proteasome inhibitor, MG132, indicating a role for proteasome-mediated degradation in HPV-associated CD1d downregulation. Taken together, our data suggest that E5 targets CD1d to the cytosolic proteolytic pathway by inhibiting calnexin-related CD1d trafficking. Finally, CD1d-mediated production of interleukin-12 from the C33A/CD1d cells was abrogated in both E5-expressing cell lines. Decreased CD1d expression in the presence of HPV E5 may help HPV-infected cells evade protective immunological surveillance.
Conserved and Variable Features of Gag Structure and Arrangement in Immature Retrovirus Particles
Authors: de Marco Alex , Davey Norman E. , Ulbrich Pavel , Phillips Judith M. , Lux Vanda , Riches James D. , Fuzik Tibor , Ruml Tomas , Kräusslich Hans-Georg , Vogt Volker M. , Briggs John A. G. 
Published: September 2010

ABSTRACT

The assembly of retroviruses is driven by oligomerization of the Gag polyprotein. We have used cryo-electron tomography together with subtomogram averaging to describe the three-dimensional structure of
in vitro
-assembled Gag particles from human immunodeficiency virus, Mason-Pfizer monkey virus, and Rous sarcoma virus. These represent three different retroviral genera: the lentiviruses, betaretroviruses and alpharetroviruses. Comparison of the three structures reveals the features of the supramolecular organization of Gag that are conserved between genera and therefore reflect general principles of Gag-Gag interactions and the features that are specific to certain genera. All three Gag proteins assemble to form approximately spherical hexameric lattices with irregular defects. In all three genera, the N-terminal domain of CA is arranged in hexameric rings around large holes. Where the rings meet, 2-fold densities, assigned to the C-terminal domain of CA, extend between adjacent rings, and link together at the 6-fold symmetry axis with a density, which extends toward the center of the particle into the nucleic acid layer. Although this general arrangement is conserved, differences can be seen throughout the CA and spacer peptide regions. These differences can be related to sequence differences among the genera. We conclude that the arrangement of the structural domains of CA is well conserved across genera, whereas the relationship between CA, the spacer peptide region, and the nucleic acid is more specific to each genus.
On distributing symmetric streaming computations
Authors: Feldman Jon , Muthukrishnan S. , Sidiropoulos Anastasios , Stein Cliff , Svitkina Zoya 
Published: September 2010

A common approach for dealing with large datasets is to stream over the input in one pass, and perform computations using sublinear resources. For truly massive datasets, however, even making a single pass over the data is prohibitive. Therefore, streaming computations must be distributed over many machines. In practice, obtaining significant speedups using distributed computation has numerous challenges including synchronization, load balancing, overcoming processor failures, and data distribution. Successful systems in practice such as Google's MapReduce and Apache's Hadoop address these problems by only allowing acertain classof highly distributable tasks defined by local computations that can be applied in any order to the input.The fundamental question that arises is: How does the class of computational tasks supported by these systems differ from the class for which streaming solutions exist?We introduce a simple algorithmic model for massive, unordered, distributed (mud) computation, as implemented by these systems. We show that in principle, mud algorithms are equivalent in power to symmetric streaming algorithms. More precisely, we show that any symmetric (order-invariant) function that can be computed by a streaming algorithm can also be computed by a mud algorithm, with comparable space and communication complexity. Our simulation uses Savitch's theorem and therefore has superpolynomial time complexity. We extend our simulation result to some natural classes of approximate and randomized streaming algorithms. We also give negative results, using communication complexity arguments to prove that extensions to private randomness, promise problems, and indeterminate functions are impossible. We also introduce an extension of the mud model to multiple keys and multiple rounds.
Metformin Prevents Tobacco Carcinogen–Induced Lung Tumorigenesis
Authors: Memmott Regan M. , Mercado Jose R. , Maier Colleen R. , Kawabata Shigeru , Fox Stephen D. , Dennis Phillip A. 
Published: September 2010

Abstract
Activation of the mammalian target of rapamycin (mTOR) pathway is an important and early event in tobacco carcinogen–induced lung tumorigenesis, and therapies that target mTOR could be effective in the prevention or treatment of lung cancer. The biguanide metformin, which is widely prescribed for the treatment of type II diabetes, might be a good candidate for lung cancer chemoprevention because it activates AMP-activated protein kinase (AMPK), which can inhibit the mTOR pathway. To test this, A/J mice were treated with oral metformin after exposure to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that are achievable in humans. mTOR was inhibited in lung tumors but only modestly. To test whether intraperitoneal administration of metformin might improve mTOR inhibition, we injected mice and assessed biomarkers in liver and lung tissues. Plasma levels of metformin were significantly higher after injection than oral administration. In liver tissue, metformin activated AMPK and inhibited mTOR. In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal–regulated kinase (ERK), and mTOR. This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of insulin-like growth factor-I receptor/insulin receptor and Akt upstream of mTOR. Based on these data, we repeated the NNK–induced lung tumorigenesis study using intraperitoneal administration of metformin. Metformin decreased tumor burden by 72%, which correlated with decreased cellular proliferation and marked inhibition of mTOR in tumors. These studies show that metformin prevents tobacco carcinogen–induced lung tumorigenesis and support clinical testing of metformin as a chemopreventive agent. Cancer Prev Res; 3(9); 1066–76. ©2010 AACR.
Quantitative Assessment of Mitral Regurgitation
Authors: Shanks Miriam , Siebelink Hans-Marc J. , Delgado Victoria , van de Veire Nico R.L. , Ng Arnold C.T. , Sieders Allard , Schuijf Joanne D. , Lamb Hildo J. , Ajmone Marsan Nina , Westenberg Jos J.M. , Kroft Lucia J. , de Roos Albert , Bax Jeroen J. 
Published: September 2010

Background—
Quantification of mitral regurgitation severity with 2-dimensional (2D) imaging techniques remains challenging. The present study compared the accuracy of 2D transesophageal echocardiography (TEE) and 3-dimensional (3D) TEE for quantification of mitral regurgitation, using MRI as the reference method.

Methods and Results—

Two-dimensional and 3D TEE and cardiac MRI were performed in 30 patients with mitral regurgitation. Mitral effective regurgitant orifice area (EROA) and regurgitant volume (Rvol) were estimated with 2D and 3D TEE. With 3D TEE, EROA was calculated using planimetry of the color Doppler flow from en face views and Rvol was derived by multiplying the EROA by the velocity time integral of the regurgitant jet. Finally, using MRI, mitral Rvol was quantified by subtracting the aortic flow volume from left ventricular stroke volume. Compared with 3D TEE, 2D TEE underestimated the EROA by a mean of 0.13 cm
2
. In addition, 2D TEE underestimated the Rvol by 21.6% when compared with 3D TEE and by 21.3% when compared with MRI. In contrast, 3D TEE underestimated the Rvol by only 1.2% when compared with MRI. Finally, one third of the patients in grade 1 and ≥50% of the patients in grade 2 and 3, as assessed with 2D TEE, would have been upgraded to a more severe grade, based on the 3D TEE and MRI measurements.

Conclusions—
Quantification of mitral EROA and Rvol with 3D TEE is feasible and accurate as compared with MRI and results in less underestimation of the Rvol as compared with 2D TEE.
Cortical Networks Representing Object Categories and High-level Attributes of Familiar Real-world Action Sounds
Authors: Lewis James W. , Talkington William J. , Puce Aina , Engel Lauren R. , Frum Chris 
Published: September 2010

AbstractIn contrast to visual object processing, relatively little is known about how the human brain processes everyday real-world sounds, transforming highly complex acoustic signals into representations of meaningful events or auditory objects. We recently reported a fourfold cortical dissociation for representing action (nonvocalization) sounds correctly categorized as having been produced by human, animal, mechanical, or environmental sources. However, it was unclear how consistent those network representations were across individuals, given potential differences between each participant's degree of familiarity with the studied sounds. Moreover, it was unclear what, if any, auditory perceptual attributes might further distinguish the four conceptual sound-source categories, potentially revealing what might drive the cortical network organization for representing acoustic knowledge. Here, we used functional magnetic resonance imaging to test participants before and after extensive listening experience with action sounds, and tested for cortices that might be sensitive to each of three different high-level perceptual attributes relating to how a listener associates or interacts with the sound source. These included the sound's perceived concreteness, effectuality (ability to be affected by the listener), and spatial scale. Despite some variation of networks for environmental sounds, our results verified the stability of a fourfold dissociation of category-specific networks for real-world action sounds both before and after familiarity training. Additionally, we identified cortical regions parametrically modulated by each of the three high-level perceptual sound attributes. We propose that these attributes contribute to the network-level encoding of category-specific acoustic knowledge representations.
Demographic and lifestyle variables associated with obesity
Authors: Worthy Sheri L , Lokken Kristine , Pilcher Kenneth , Boeka Abbe 
Published: September 2010

Objective: Overweight and obesity rates are associated with chronic diseases and higher rates of disability and continue to rise in the United States and worldwide. The purpose of this study was to build on past research and further investigate demographic and lifestyle variables associated with increased body mass index (BMI: kg/m 2). Methods: Personal Information Worksheets were completed by 125 bariatric surgery candidates and 213 community dwelling individuals providing a sample size of 338. Hierarchical regression analysis was performed on three sets of independent variables (demographic characteristics, lifestyle variables and consumer response) and one dependent variable (BMI). Results: Lower levels of education and physical activity, higher levels of diet soda consumption and number of dieting attempts, and likelihood of starting a diet programme based on advertising testimonials were predictive of higher BMI. Conclusion: This research highlights the need for more education emphasizing the importance of increased healthy behaviours versus use of diet products and fad diets to improve success of weight loss efforts.
Are incentive schemes effective in changing young people’s behaviour? A systematic review
Authors: Kavanagh Josephine , Oakley Ann , Harden Angela , Trouton Alex , Powell Chloe 
Published: September 2010

Objective: To examine the impact of single or dual component incentive schemes on health and social behaviours, in young people. Design: A systematic review. Method: Systematic and comprehensive cross-disciplinary searches were conducted to identify research. Following screening for relevance, included studies were quality assessed and data extracted. Both outcome and process evaluation studies were included in either a statistical meta-analysis or narrative synthesis. Results: Sixteen trials and seven process evaluations were included in the review. There is some evidence to show that incentives are effective in improving single health behaviours, but not complex health behaviours. Incentives had no impact on levels of reported effort, or attendance in education studies. Whilst viewed favourably by young people, incentives did not necessarily translate into improvements in targeted behaviours. Conclusion: Evidence suggests that incentives schemes do not provide policy makers or practitioners with a simple route to improving young people’s health or other behaviours. However, there is evidence that incentives can be useful in encouraging positive health behaviour change where a simple or single action is required.
The impact of additional weekdays of active commuting to school on children achieving a criterion of 300+ minutes of moderate-to-vigorous physical activity
Authors: Daly-Smith Andy JW , McKenna Jim , Radley Duncan , Long Jonathan 
Published: September 2010

Objective: To investigate the value of additional days of active commuting for meeting a criterion of 300+ minutes of moderate-to-vigorous physical activity (MVPA; 60+ mins/day x 5) during the school week. Methods: Based on seven-day diaries supported by teachers, binary logistic regression analyses were used to predict achievement of MVPA criteria according to days of active commuting to and from school. MVPA was recorded across five time points: (a) before school, (b) walking/cycling to and from school, (c) during school, (d) in school-based clubs and (e) during leisure time. The study was conducted in Derby, UK, in June 2006. Results: Active commuting was reported by 4218 (78 per cent of 5422) children for an average daily commuting time of 18.4 ± 16.4 minutes. Children who commuted on more days in the week were most likely to achieve the MVPA criterion. Every day of active commuting doubled the chances of meeting the MVPA criterion; in Year 10 girls this effect was stronger (odds ratio 6.45). Conclusion: Results confirm the ubiquity of active commuting among young people. Even one additional day of active commuting helps to meet established criteria. In older girls active commuting is uniquely powerful in contributing to attainment of public health targets of MVPA.
Visual impairment and self-esteem
Authors: Bowen Jayne 
Published: September 2010

This account follows on from the research report ‘Visual impairment and its impact on self-esteem’ (Bowen, 2010) published in this journal. The original article reported the results of an investigation of self-esteem levels amongst a sample group of 60 children with visual impairment. Four children, whose self-esteem was measured as ‘low’ or ‘very low’ on the B/G STEEM (1993) at the outset of the study were provided with educational programmes in school designed to enhance self-esteem, and their self-esteem was subsequently re-tested on two further occasions. The strategic interventions trialled were ‘circle time’, ‘circle of friends’ and individual mentoring. The interventions were trialled singly and in combination. There was no conclusive evidence that any one strategic intervention, or combination of interventions, was more successful at enhancing self-esteem than any other. However, three out of the four pupils had achieved higher scores for self-esteem by the second assessment; all of them had increased self-esteem levels by the third assessment six months later; and their schools openly commented about the benefits of the interventions for the young people concerned. Possible explanations for the apparent improvements in the target children are offered.
Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile
Authors: Martinelli Nicola , Girelli Domenico , Lunghi Barbara , Pinotti Mirko , Marchetti Giovanna , Malerba Giovanni , Pignatti Pier Franco , Corrocher Roberto , Olivieri Oliviero , Bernardi Francesco 
Published: September 2010

AbstractHigh levels of coagulation factor VIII (FVIII) have been associated with cardiovascular disease. Low-density lipoprotein receptor (LDLR) has been recently demonstrated to contribute to FVIII clearance from plasma. The aim of this study was to evaluate 3 single nucleotide polymorphisms in SMARCA4-LDLR gene locus (rs1122608, rs2228671, and rs688) and FVIII coagulant activity (FVIII:c) in subjects with (n = 692) or without (n = 291) angiographically confirmed coronary artery disease (CAD). High FVIII:c levels were an independent risk factor for CAD. The rs688 and rs2228671 genotypes were predictors of FVIII:c with T alleles associated with higher FVIII:c levels. The rs2228671T allele was associated also with reduced total and LDL-cholesterol levels. With respect to the risk of CAD, no association was found for rs2228671. Consistently with higher FVIII:c levels, the rs688T allele was associated with CAD, whereas, consistently with a favorable lipid profile, the rs1122608T allele was associated with a decreased CAD prevalence. After adjustment for classic cardiovascular risk factors, including plasma lipids, rs688 remained associated with CAD (OR for T carriers: 1.67 with 95% confidence interval, 1.10-2.54). Haplotype analysis confirmed such results. Our data suggest that polymorphisms at LDLR locus modulate FVIII:c levels and may be associated with CAD risk independently from plasma lipids.
Distinct patterns of mitochondrial genome diversity in bonobos (Pan paniscus) and humans
Authors: Zsurka Gábor , Kudina Tatiana , Peeva Viktoriya , Hallmann Kerstin , Elger Christian E , Khrapko Konstantin , Kunz Wolfram S 
Published: September 2010

Abstract

Background
We have analyzed the complete mitochondrial genomes of 22 Pan paniscus (bonobo, pygmy chimpanzee) individuals to assess the detailed mitochondrial DNA (mtDNA) phylogeny of this close relative of Homo sapiens.

Results
We identified three major clades among bonobos that separated approximately 540,000 years ago, as suggested by Bayesian analysis. Incidentally, we discovered that the current reference sequence for bonobo likely is a hybrid of the mitochondrial genomes of two distant individuals. When comparing spectra of polymorphic mtDNA sites in bonobos and humans, we observed two major differences: (i) Of all 31 bonobo mtDNA homoplasies, i.e. nucleotide changes that occurred independently on separate branches of the phylogenetic tree, 13 were not homoplasic in humans. This indicates that at least a part of the unstable sites of the mitochondrial genome is species-specific and difficult to be explained on the basis of a mutational hotspot concept. (ii) A comparison of the ratios of non-synonymous to synonymous changes (d

N

/d

S
) among polymorphic positions in bonobos and in 4902 Homo sapiens mitochondrial genomes revealed a remarkable difference in the strength of purifying selection in the mitochondrial genes of the F0F1-ATPase complex. While in bonobos this complex showed a similar low value as complexes I and IV, human haplogroups displayed 2.2 to 7.6 times increased d

N

/d

S
ratios when compared to bonobos.

Conclusions
Some variants of mitochondrially encoded subunits of the ATPase complex in humans very likely decrease the efficiency of energy conversion leading to production of extra heat. Thus, we hypothesize that the species-specific release of evolutionary constraints for the mitochondrial genes of the proton-translocating ATPase is a consequence of altered heat homeostasis in modern humans.
The chicken miR-150 targets the avian orthologue of the functional zebrafish MYB 3'UTR target site
Authors: Guillon-Munos Audrey , Dambrine Ginette , Richerioux Nicolas , Coupeau Damien , Muylkens Benoît , Rasschaert Denis 
Published: September 2010

Abstract

Background
The c-myb proto-oncogene is the founding member of a family of transcription factors involved principally in haematopoiesis, in diverse organisms, from zebrafish to mammals. Its deregulation has been implicated in human leukaemogenesis and other cancers. The expression of c-myb is tightly regulated by post-transcriptional mechanisms involving microRNAs. MicroRNAs are small, highly conserved non-coding RNAs that inhibit translation and decrease mRNA stability by binding to regulatory motifs mostly located in the 3'UTR of target mRNAs conserved throughout evolution. MYB is an evolutionarily conserved miR-150 target experimentally validated in mice, humans and zebrafish. However, the functional miR-150 sites of humans and mice are orthologous, whereas that of zebrafish is different.

Results
We identified the avian mature miRNA-150-5P, Gallus gallus gga-miR-150 from chicken leukocyte small-RNA libraries and showed that, as expected, the gga-miR-150 sequence was highly conserved, including the seed region sequence present in the other miR-150 sequences listed in miRBase. Reporter assays showed that gga-miR-150 acted on the avian MYB 3'UTR and identified the avian MYB target site involved in gga-miR-150 binding. A comparative in silico analysis of the miR-150 target sites of MYB 3'UTRs from different species led to the identification of a single set of putative target sites in amphibians and zebrafish, whereas two sets of putative target sites were identified in chicken and mammals. However, only the target site present in the chicken MYB 3'UTR that was identical to that in zebrafish was functional, despite the additional presence of mammalian target sites in chicken. This specific miR-150 site usage was not cell-type specific and persisted when the chicken c-myb 3'UTR was used in the cell system to identify mammalian target sites, showing that this miR-150 target site usage was intrinsic to the chicken c-myb 3'UTR.

Conclusion
Our study of the avian MYB/gga-miR-150 interaction shows a conservation of miR-150 target site functionality between chicken and zebrafish that does not extend to mammals.