bluuebunny/crossref_metadata_2025_split huggingface dataset:
The E4orf6/E1B55K E3 Ubiquitin Ligase Complexes of Human Adenoviruses Exhibit Heterogeneity in Composition and Substrate Specificity
Authors: Cheng Chi Ying , Gilson Timra , Dallaire Frédéric , Ketner Gary , Branton Philip E. , Blanchette Paola 
Published: November 2010

ABSTRACT
Although human adenovirus type 5 (Ad5) has been widely studied, relatively little work has been done with other human adenovirus serotypes. The Ad5 E4orf6 and E1B55K proteins form Cul5-based E3 ubiquitin ligase complexes to degrade p53, Mre11, DNA ligase IV, integrin α3, and almost certainly other targets, presumably to optimize the cellular environment for viral replication and perhaps to facilitate persistence or latency. As this complex is essential for the efficient replication of Ad5, we undertook a systematic analysis of the structure and function of corresponding E4orf6/E1B55K complexes from other serotypes to determine the importance of this E3 ligase throughout adenovirus evolution. E4orf6 and E1B55K coding sequences from serotypes representing all subgroups were cloned, and each pair was expressed and analyzed for their capacity to assemble the Cullin-based ligase complex and to degrade substrates following plasmid DNA transfection. The results indicated that all formed Cullin-based E3 ligase complexes but that heterogeneity in both structure and function existed. Whereas Cul5 was present in the complexes of some serotypes, others recruited primarily Cul2, and the Ad16 complex clearly bound both Cul2 and Cul5. There was also heterogeneity in substrate specificity. Whereas all serotypes tested appeared to degrade DNA ligase IV, complexes from some serotypes failed to degrade Mre11, p53, or integrin α3. Thus, a major evolutionary pressure for formation of the adenovirus ligase complex may lie in the degradation of DNA ligase IV; however, it seems possible that the degradation of as-yet-unidentified critical targets or, perhaps even more likely, appropriate combinations of substrates plays a central role for these adenoviruses.
The Presence of a
vpu
Gene and the Lack of Nef-Mediated Downmodulation of T Cell Receptor-CD3 Are Not Always Linked in Primate Lentiviruses
Authors: Schmökel Jan , Sauter Daniel , Schindler Michael , Leendertz Fabian H. , Bailes Elizabeth , Dazza Marie-Christine , Saragosti Sentob , Bibollet-Ruche Frederic , Peeters Martine , Hahn Beatrice H. , Kirchhoff Frank 
Published: November 2010

ABSTRACT

Nef is an accessory protein critical for the ability of human and simian immunodeficiency viruses (HIV and SIV) to replicate efficiently in their respective hosts. Previous analyses of members of 15 different primate lentivirus lineages revealed a link between Nef function and the presence of a
vpu
gene. In particular, Nef proteins of all
vpu
-containing viruses had lost their ability to downmodulate the T cell (TCR-CD3) receptor. Here we examined Nef proteins from eight additional SIV lineages, including SIVgor, SIVwrc, SIVolc, SIVgri, SIVdrl, SIVlho, SIVden, and SIVasc, from western lowland gorillas, western red colobus monkeys, olive colobus monkeys, grivet monkeys, drills, L'Hoest's monkeys, Dent's mona monkeys, and red-tailed monkeys, respectively. We found that except for the
nef
gene of SIVdrl, all of them were efficiently expressed and modulated CD4, major histocompatibility complex class I (MHC-I), CD28, CXCR4, and Ii cell surface expression and/or enhanced viral infectivity and replication. Furthermore, the Nef proteins of SIVgri, SIVlho, SIVwrc, SIVolc, and SIVgor antagonized tetherin. As expected, the Nef protein of SIVgor, which carries
vpu
, failed to downmodulate CD3, whereas those of SIVwrc, SIVgri, SIVlho, and SIVasc, which lack
vpu
, were capable of performing this function. Surprisingly, however, the Nef protein of the
vpu
-containing SIVden strain retained the ability to downmodulate TCR-CD3, whereas that of SIVolc, which does not contain
vpu
, was unable to perform this function. Although the SIVden Vpu is about 20 amino acids shorter than other Vpu proteins, it degrades CD4 and antagonizes tetherin. Our data show that there are exceptions to the link between the presence of a
vpu
gene and
nef
alleles deficient in CD3 modulation, indicating that host properties also affect the selective pressure for Nef-mediated disruption of TCR-CD3 signaling. Our results are also further evidence that tetherin antagonism is a common function of primate lentivirus Nef proteins and that the resistance of human tetherin to Nef represents a relevant barrier to cross-species transmission of SIVs to humans.
Composts containing fluorescent pseudomonads suppress fusarium root and stem rot development on greenhouse cucumber
Authors: Bradley Geoffrey G. , Punja Zamir K. 
Published: November 2010

Three composts (Ball, dairy, and greenhouse) were tested for the ability to suppress the development of Fusarium root and stem rot (caused by Fusarium oxysporum f. sp. radicis-cucumerinum) on greenhouse cucumber. Dairy and greenhouse composts significantly reduced disease severity (P = 0.05), while Ball compost had no effect. Assessment of total culturable microbes in the composts showed a positive relationship between disease suppressive ability and total population levels of pseudomonads. In vitro antagonism assays between compost-isolated bacterial strains and the pathogen showed that strains of Pseudomonas aeruginosa exhibited the greatest antagonism. In growth room trials, strains of P. aeruginosa and nonantagonistic Pseudomonas maculicola , plus 2 biocontrol strains of Pseudomonas fluorescens , were tested for their ability to reduce (i) survival of F. oxysporum, (ii) colonization of plants by the pathogen, and (iii) disease severity. Cucumber seedlings grown in compost receiving P. aeruginosa and P. fluorescens had reduced disease severity index scores after 8 weeks compared with control plants without bacteria. Internal stem colonization by F. oxysporum was significantly reduced by P. aeruginosa. The bacteria colonized plant roots at 1.9 × 106 ± 0.73 × 106CFU·(g root tissue)–1and survival was >107 CFU·(g compost)–1after 6 weeks. The locus for 2,4-diacetylphloroglucinol production was detected by Southern blot analysis and confirmed by PCR. The production of the antibiotic 2,4-diacetylphloroglucinol in liquid culture by P. aeruginosa was confirmed by thin layer chromatography. These results demonstrate that composts containing antibiotic-producing P. aeruginosa have the potential to suppress diseases caused by Fusarium species.
Recombinant Porphyromonas gingivalis FimA preproprotein expressed in Escherichia coli is lipidated and the mature or processed recombinant FimA protein forms a short filament in vitro
Authors: Shoji Mikio , Yoshimura Atsutoshi , Yoshioka Hidenobu , Takade Akemi , Takuma Yasuko , Yukitake Hideharu , Naito Mariko , Hara Yoshitaka , Yoshida Shin-Ichi , Nakayama Koji 
Published: November 2010

The gram-negative anaerobic bacterium Porphyromonas gingivalis is an etiologically important pathogen for chronic periodontal diseases in adults. Our previous study suggested that the major structural components of both Fim and Mfa fimbriae in this organism are secreted through their lipidated precursors. In this study, we constructed Escherichia coli strains expressing various fimA genes with or without the 5′-terminal DNA region encoding the signal peptide, and we determined whether lipidation of recombinant FimA proteins occurred in E. coli. Lipidation occurred for a recombinant protein from the fimA gene with the 5′-terminal DNA region encoding the signal peptide but not for a recombinant protein from the fimA gene without the signal-peptide-encoding region, as revealed by [3H]palmitic acid labeling experiments. A TLR2-dependent signaling response was induced by the recombinant protein from the fimA gene with the signal-peptide-encoding region but not by a recombinant protein from the fimA gene with the signal-peptide-encoding region that had a base substitution causing an amino acid substitution (C19A). Electron microscopic analysis revealed that recombinant FimA (A-47 – W-383) protein was autopolymerized to form filamentous structures of about 80 nm in length in vitro. The results suggest that FimA protein, a major subunit of Fim fimbriae, is transported to the outer membrane by the lipoprotein sorting system, and a mature or processed FimA protein on the outer membrane is autopolymerized to form Fim fimbriae.
Effects of low-dose ketanserin on atherosclerosis in rats and rabbits
Authors: Yu Yong-Sheng , Xie He-Hui , Li Ling , Song Shu-Wei , Han Ping , Cai Guo-Jun , Su Ding-Feng 
Published: November 2010

The present study was designed to test the hypothesis that a small dose of ketanserin, which enhances baroreflex activity, prevents the early lesions of atherosclerosis. In experiment 1, baroreflex sensitivity (BRS) was measured in 31 spontaneously hypertensive rats (SHRs) in a conscious state using a computerized blood pressure monitoring system. Four weeks later, the rats were administered vitamin D3and fed a high-cholesterol diet for 8 weeks to induce atherosclerosis. Then their hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r = –0.460, P < 0.01) and aortic atherosclerosis (r = –0.448, P < 0.05) in SHR. In experiment 2, SHRs were divided into 3 groups (n = 10 in each group) and received a dose of ketanserin of 0.3, 1.0, and 3.0 mg/kg (i.g.), respectively. At the smallest dose (0.3 mg/kg), ketanserin did not lower blood pressure but enhanced BRS. In experiment 3, SHRs were administered vitamin D3, fed a high-cholesterol diet, and simultaneously treated with low-dose ketanserin. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (coronary score: 0.90 ± 0.14 vs. 1.76 ± 0.27, P < 0.05; aortic scores: 1.00 ± 0.39 vs. 2.18 ± 0.41, P < 0.05). In experiment 4, male New Zealand White rabbits were fed a high-cholesterol diet and treated with low-dose ketanserin at the same time. The atherosclerosis scores of the treatment group were significantly lower than those of the control group (aortic scores: 0.26 ± 0.20 vs. 0.60 ± 0.31, P < 0.05). In conclusion, the present study demonstrated, for the first time, that low-dose ketanserin prevented the development of atherosclerosis independent of its blood pressure lowering action in SHRs and New Zealand White rabbits at least in part via enhancement of arterial baroreflex function.
Sequential alterations in Akt, GSK3β, and calcineurin signalling in the mouse left ventricle after thoracic aortic constriction
Authors: Prévilon Miresta , Pezet Mylène , Dachez Céline , Mercadier Jean-Jacques , Rouet-Benzineb Patricia 
Published: November 2010

Left ventricular hypertrophy (LVH) is an adaptive response to chronic biomechanical stress that generally progresses to maladaptive hypertrophy and heart failure (HF). We studied the activation of protein kinase B (Akt/PKB), glycogen synthase kinase 3 beta (GSK3β), and calcineurin (Cn) at 3, 7, 15, 30, and 60 days following transverse aortic constriction (TAC) in 4-week-old mice. Following TAC, GSK3β inactivation at day 3 was associated with Akt activation, whereas at days 15 and 30, it appeared to be controlled by other kinases. Moderate nonsignificant Cn activation occurred at the early stages, and peak activation at day 30, concomitant with GSK3β inactivation and overt LVH and HF. At the latest stage (day 60), despite further progression of LVH and HF, Cn activation appeared attenuated. Early stages of LVH were associated with Ca2+-handling protein upregulation, whereas major Cn activation, associated with GSK3β inactivation, appeared to engage maladaptive hypertrophy and progression to HF associated with Ca2+-handling protein downregulation.
Factors Associated With Outcome in Heart Failure With Preserved Ejection Fraction
Authors: Komajda Michel , Carson Peter E. , Hetzel Scott , McKelvie Robert , McMurray John , Ptaszynska Agata , Zile Michael R. , DeMets David , Massie Barry M. 
Published: November 2010

Background—
The determinants of prognosis in patients with heart failure and preserved ejection fraction (HF-PEF) are poorly documented.

Methods and Results—
We evaluated data from 4128 patients in the I-PRESERVE trial (Irbesartan in Heart Failure with Preserved Ejection Fraction Study). Multivariable Cox regression models were developed using 58 baseline demographic, clinical, and biological variables to model the primary outcome of all-cause mortality or cardiovascular hospitalization (1505 events), all-cause mortality (881 events), and HF death or hospitalization (716 events). Log N-terminal pro–B-type natriuretic peptide, age, diabetes mellitus, and previous hospitalization for HF were the most powerful factors associated with the primary outcome and with the HF composite. For all-cause mortality, log N-terminal pro–B-type natriuretic peptide, age, diabetes mellitus, and left ventricular EF were the strongest independent factors. Other independent factors associated with poor outcome included quality of life, a history of chronic obstructive lung disease, log neutrophil count, heart rate, and estimated glomerular filtration rate. The models accurately stratified the actual 3-year rate of outcomes from 8.1% to 59.9% (primary outcome) 2.7% to 36.5% (all-cause mortality), and 2.1% to 38.9% (HF composite) for the lowest to highest septiles of predicted risks.

Conclusions—
In a large sample of elderly patients with HF and preserved EF enrolled in I-Preserve, simple clinical, demographic, and biological variables were associated with outcome and identified subgroups at very high and very low risk of events.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00095238.
Another Citation of Philo in Clement of Alexandria’s Protrepticus (10,93,1-2)
Authors: Dinan Andrew 
Published: November 2010

AbstractProt. 10,93,1-2 should be added to the long list of passages in which Clement has made use of the writings of Philo. Clement is attracted by, and in large measure appropriates, Philo’s description of repentance in Virt. 181, yet he alters the Philonic text in several ways, notably by making explicit a citation that also appears partially in Plato, Phd 114D and more fully in Horace, C. 3,25.
The Active Nature of the Soul in Sense Perception: Robert Kilwardby and Peter Olivi
Authors: Silva José Filipe , Toivanen Juhana 
Published: November 2010

AbstractThis article discusses the theories of perception of Robert Kilwardby and Peter of John Olivi. Our aim is to show how in challenging certain assumptions of medieval Aristotelian theories of perception they drew on Augustine and argued for the active nature of the soul in sense perception. For both Kilwardby and Olivi, the soul is not passive with respect to perceived objects; rather, it causes its own cognitive acts with respect to external objects and thus allows the subject to perceive them. We also show that Kilwardby and Olivi differ substantially regarding where the activity of the soul is directed to and the role of the sensible species in the process, and we demonstrate that there are similarities between their ideas of intentionality and the attention of the soul towards the corporeal world.
Ontological Insecurity: A Guiding Framework for Borderline Personality Disorder
Authors: Wilson John , McDonald Matthew , Pietsch Tina 
Published: November 2010

AbstractThe purpose of this inquiry is to explore the experience of Borderline Personality Disorder with the aim of developing a more liberating approach to its diagnosis and treatment. Eight participants (seven females and one male) diagnosed with Borderline Personality Disorder were recruited from a psychiatric hospital operated by the Surrey and Borders NHS Trust and an outpatient daycentre based in London, United Kingdom. A narrative approach to methodology was employed to collect and analyse the participants’ life-stories. Themes to emerge from the participant’s narratives were found to coincide with R.D. Laing’s concept of ontological insecurity. Ontological insecurity describes a number of aspects of the participant’s distress. To conclude, some general implications of this research for psychotherapy are briefly explored.
Forms of Hate Speech and the Convention on the Elimination of all Forms of Racial Discrimination (ICERD)
Authors: Thornberry Patrick 
Published: November 2010

AbstractIn this article, issues are raised concerning freedom of expression and forms of hate speech including advocacy of religious hatred in light of proposals to combat defamation of religions. In particular, it is asked whether parallels can be drawn between freedom of expression and protection from forms of hate speech in the area of race and ethnicity, and expression and protection in the field of religion. The present article offers a brief summary of relevant ICERD (‘the Convention’)<xref ref-type="fn" rid="FN1">2</xref> principles and practice. The sketch of principles revolves around key areas of the Convention: the concept of discrimination including the ‘grounds’ of prohibited discrimination and how they relate to religious groups; the Convention’s stance on hate speech and rights to freedom of thought, conscience and religion<xref ref-type="fn" rid="FN2">3</xref> and freedom of opinion and expression.<xref ref-type="fn" rid="FN3">4</xref> The concluding section reflects on the concept of defamation of religions, the boundaries of ICERD in its current interpretation, and the idea of ICERD as a model for wider exercises in standard setting. The Committee on the Elimination of Discrimination (CERD) has the longest practice of any treaty body in the fields within its mandate and has developed a distinctive discourse in key areas. ‘Hate speech’ in the present article is used as shorthand for a range of international provisions protecting individuals and groups from discrimination and other assaults on their dignity and does not imply a special definition beyond the examples cited.
Circulating human CD4 and CD8 T cells do not have large intracellular pools of CCR5
Authors: Pilch-Cooper Heather A. , Sieg Scott F. , Hope Thomas J. , Koons Ann , Escola Jean-Michel , Offord Robin , Veazey Ronald S. , Mosier Donald E. , Clagett Brian , Medvik Kathy , Jadlowsky Julie K. , Chance Mark R. , Kiselar Janna G. , Hoxie James A. , Collman Ronald G. , Riddick Nadeene E. , Mercanti Valentina , Hartley Oliver , Lederman Michael M. 
Published: November 2010

AbstractCC Chemokine Receptor 5 (CCR5) is an important mediator of chemotaxis and the primary coreceptor for HIV-1. A recent report by other researchers suggested that primary T cells harbor pools of intracellular CCR5. With the use of a series of complementary techniques to measure CCR5 expression (antibody labeling, Western blot, quantitative reverse transcription polymerase chain reaction), we established that intracellular pools of CCR5 do not exist and that the results obtained by the other researchers were false-positives that arose because of the generation of irrelevant binding sites for anti-CCR5 antibodies during fixation and permeabilization of cells.
The Caenorhabditis elegansCDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells
Authors: Poulin Gino B , Ahringer Julie 
Published: November 2010

Abstract
Background
Attenuation of the EGFR (Epidermal Growth Factor Receptor) signalling cascade is crucial to control cell fate during development. A candidate-based RNAi approach in C. elegans identified CDT-2 as an attenuator of LET-23 (EGFR) signalling. Human CDT2 is a component of the conserved CDT2/CUL4/DDB1 ubiquitin ligase complex that plays a critical role in DNA replication and G2/M checkpoint. Within this complex, CDT2 is responsible for substrate recognition. This ubiquitin ligase complex has been shown in various organisms, including C. elegans, to target the replication-licensing factor CDT1, and the CDK inhibitor p21. However, no previous link to EGFR signalling has been identified.

Results
We have characterised CDT-2's role during vulva development and found that it is a novel attenuator of LET-23 signalling. CDT-2 acts redundantly with negative modulators of LET-23 signalling and CDT-2 or CUL-4 downregulation causes persistent expression of the egl-17::cfp transgene, a marker of LET-23 signalling during vulva development. In addition, we show that CDT-2 physically interacts with SEM-5 (GRB2), a known negative modulator of LET-23 signalling that directly binds LET-23, and provide genetic evidence consistent with CDT-2 functioning at or downstream of LET-23. Interestingly, both SEM-5 and CDT-2 were identified independently in a screen for genes involved in receptor-mediated endocytosis in oocytes, suggesting that attenuation of LET-23 by CDT-2 might be through regulation of endocytosis.

Conclusions
In this study, we have shown that CDT-2 and CUL-4, members of the CUL-4/DDB-1/CDT-2 E3 ubiquitin ligase complex attenuate LET-23 signalling in vulval precursor cells. In future, it will be interesting to investigate the potential link to endocytosis and to determine whether other signalling pathways dependent on endocytosis, e.g. LIN-12 (Notch) could be regulated by this ubiquitin ligase complex. This work has uncovered a novel function for the CUL-4/DDB-1/CDT-2 E3 ligase that may be relevant for its mammalian oncogenic activity.
Genetic variation in the odorant receptors family 13 and the mhc loci influence mate selection in a multiple sclerosis dataset
Authors: Khankhanian Pouya , Gourraud Pierre-Antoine , Caillier Stacy J , Santaniello Adam , Hauser Stephen L , Baranzini Sergio E , Oksenberg Jorge R 
Published: November 2010

AbstractBackgroundWhen selecting mates, many vertebrate species seek partners with major histocompatibility complex (MHC) genes different from their own, presumably in response to selective pressure against inbreeding and towards MHC diversity. Attempts at replication of these genetic results in human studies, however, have reached conflicting conclusions.ResultsUsing a multi-analytical strategy, we report validated genome-wide relationships between genetic identity and human mate choice in 930 couples of European ancestry. We found significant similarity between spouses in the MHC at class I region in chromosome 6p21, and at the odorant receptor family 13 locus in chromosome 9. Conversely, there was significant dissimilarity in the MHC class II region, near theHLA-DQA1and -DQB1genes. We also found that genomic regions with significant similarity between spouses show excessive homozygosity in the general population (assessed in the HapMap CEU dataset). Conversely, loci that were significantly dissimilar among spouses were more likely to show excessive heterozygosity in the general population.ConclusionsThis study highlights complex patterns of genomic identity among partners in unrelated couples, consistent with a multi-faceted role for genetic factors in mate choice behavior in human populations.