bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretory vesicle aminopeptidase B related to neuropeptide processing: molecular identification and subcellular localization to enkephalin‐ and NPY‐containing chromaffin granules
Authors: Hwang Shin‐Rong , O’Neill Audrey , Bark Steven , Foulon Thierry , Hook Vivian 
Published: January 2007

AbstractBiosynthesis of peptide hormones and neurotransmittters involves proteolysis of proprotein precursors by secretory vesicle cathepsin L. Cathepsin L generates peptide intermediates with basic residues at their NH2‐termini, indicating that Arg/Lys aminopeptidase is needed to generate the smaller biologically active peptide. Therefore, this study identified the Arg/Lys aminopeptidase that is present in secretory vesicles of adrenal medulla and neuroendocrine tissues, achieved by molecular cloning and localization in ‘model’ neuropeptide‐containing secretory vesicles (bovine). Molecular cloning of the bovine aminopeptidase B (AP‐B) cDNA defined its primary sequence that allowed selection of antisera for immunolocalization studies. AP‐B was present in secretory vesicles that contain cathepsin L with the neuropeptides enkephalin and neuropeptide Y. The AP‐B in several neuroendocrine tissues was detected by western blots. Recombinant bovine AP‐B showed preference for Arg‐methylcoumarinamide substrate. AP‐B was inhibited by arphamenine, an inhibitor of aminopeptidases. Bovine AP‐B showed similar activities for Arg‐(Met)enkephalin (ME) and Lys‐ME neuropeptide substrates to generate ME, while rat AP‐B preferred Arg‐ME. Furthermore, AP‐B possesses an acidic pH optimum of 5.5–6.5 that is similar to the internal pH of secretory vesicles. The significant finding of the secretory vesicle localization of AP‐B with neuropeptides and cathepsin L suggests a role for this exopeptidase in the biosynthesis of neuropeptides.
Alterations in lipid homeostasis of mouse dorsal root ganglia induced by apolipoprotein E deficiency: a shotgun lipidomics study
Authors: Cheng Hua , Jiang Xuntian , Han Xianlin 
Published: January 2007

AbstractOne of the fundamental goals of lipidomics research is to identify the linkage of an individual gene with a given lipidome, thereby revealing the role of that gene in lipid metabolism, transport, and homeostasis. In this study, we have identified four apolipoprotein E (apoE)‐induced alterations in the lipidome of mouse dorsal root ganglia (DRG) through utilizing the technology of shotgun lipidomics. First, apoE mediates sulfatide mass content in mouse DRG, which is comparable to its role in the CNS. Second, apoE contributes to galactosylceramide and ceramide homeostasis in mouse DRG. Third, apoE significantly modulates cholesterol levels in mouse DRG. The latter two functions of apoE are distinct from those in the CNS. Finally, mice null for apoE have dramatically less triacylglycerol mass content in DRG which are opposite to the effects observed in the peripheral organs and vascular system. Collectively, this study identifies the specific alterations in the DRG lipidome induced by apoE knockout and suggests the potential roles of apoE in lipid transport and homeostasis in a tissue specific manner, thereby providing insights into the biochemical mechanisms underlying the functions of apoE in the PNS.
Vardenafil Restores Erectile Function to Normal Range in Men with Erectile Dysfunction
Authors: Padma-Nathan Harin , Montorsi Francesco , Giuliano François , Meuleman Eric , Auerbach Stephen , Eardley Ian , McCullough Andrew , Homering Martin , Segerson Thomas ,   for the North American and European Vardenafil Study Group
Published: January 2007

ABSTRACT

Introduction
The ability of oral phosphodiesterase type 5 (PDE5) inhibitor therapy to restore erectile function to normal is an important attribute to men with erectile dysfunction (ED).

Aim
To assess the ability of vardenafil to restore normal erectile function in men with general ED.

Methods
In two fixed-dose, parallel-group, double-blind, placebo-controlled, pivotal studies, patients received vardenafil (5, 10, or 20 mg) or placebo for 12/26 weeks.

Main Outcome Measure
In this retrospective analysis, the percentage of patients “returning to normal” erectile function at week 12 (as defined by scores ≥26 on erectile function domain of International Index of Erectile Function [IIEF-EF]) was determined, with further stratification by baseline ED severity, etiology, age, and duration of ED.

Results
Vardenafil 5, 10, and 20 mg returned 32%, 43%, and 49% of patients, respectively, to normal erectile function after 12 weeks, compared with 10% of patients receiving placebo (P &lt;0.0001). Return to normal IIEF-EF domain scores was noted irrespective of severity, etiology, age, and duration of ED, and was observed even in challenging-to-treat subgroups. With vardenafil 20 mg, 39% of men with severe ED at baseline, 45–49% of men with ED of mixed or organic etiology, 35% of men aged ≥65 years, and 43% of men with ED of ≥3 years of duration returned to normal erectile function at week 12. Mean per-patient SEP3 (question 3 on the Sexual Encounter Profile) success rates in patients achieving IIEF-EF domain scores ≥26 ranged from 87% to 95%.

Conclusion
Vardenafil improves the IIEF-EF domain score to the normal range in a substantial proportion of men with ED.
Quality of Erection Questionnaire Correlates: Change in Erection Quality with Erectile Function, Hardness, and Psychosocial Measures in Men Treated with Sildenafil for Erectile Dysfunction
Authors: Lowy Michael , Collins Suzanne , Bloch Mark , Gillman Michael , Lording Douglas , Sutherland Peter , Wang Hao , Stecher Vera 
Published: January 2007

ABSTRACT

Introduction
The validated Quality of Erection Questionnaire (QEQ) is a six-question, patient-reported outcome measure for comprehensively evaluating satisfaction with the quality of erections in terms of hardness, onset, and duration, which can be used to develop and monitor individualized treatment goals.

Aims
To further validate the QEQ by determining responsiveness/sensitivity to change in erectile function, erection hardness grade, and psychosocial outcomes in men treated with sildenafil for erectile dysfunction (ED).

Methods
This open-label, noncomparative, multicenter trial of sildenafil (50 or 100 mg as needed for 10 weeks) enrolled men with ED who were in a stable, sexual relationship for at least 6 months. Previous phosphodiesterase type 5 inhibitor use must have been no more than 6 doses ever and no doses more recently than the previous 4 weeks.

Main Outcome Measures
The baseline to week 10 change in the QEQ total score and its correlations with the end-of-treatment Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score and with changes in: (i) International Index of Erectile Function (IIEF) domain scores; (ii) Self-Esteem And Relationship (SEAR) questionnaire component scores; and (iii) the frequency of erections graded hard enough for penetration (grade 3) or completely hard (grade 4) on the event log Erectile Hardness Grading Scale.

Results
The mean ± standard deviation transformed QEQ total score tripled from 22.0 ± 21.1 to 69.9 ± 35.9 (P &lt;0.0001), and correlated positively with the end-of-treatment EDITS index score (r = 0.71) and with changes in IIEF domain scores (r =0.29–0.86), SEAR component scores (r = 0.37–0.78), and the percentage of occasions that grade 3 or 4 erections were achieved (r =0.66).

Conclusion
The brief, easy-to-administer QEQ is responsive to the benefits of sildenafil treatment of men for ED and has convergent validity with measures of clinical and psychosocial outcomes.
GEOLOGICAL MODEL EVALUATION THROUGH WELL TEST SIMULATION: A CASE STUDY FROM THE WYTCH FARM OILFIELD, SOUTHERN ENGLAND
Authors: Zheng S.Y. , Legrand V. M. , Corbett P.W.M. 
Published: January 2007

This paper presents an approach to the evaluation of reservoir models using transient pressure data. Braided fluvial sandstones exposed in cliffs in SW England were studied as the surface equivalent of the Triassic Sherwood Sandstone, a reservoir unit at the nearby Wytch Farm oilfield. Three reservoir models were built; each used a different modelling approach ranging in complexity from stochastic pixel‐based modelling using commercially available software, to a spreadsheet random number generator. In order to test these models, numerical well test simulations were conducted using sector models extracted from the geological models constructed. The simulation results were then evaluated against the actual well test data in order to find the model which best represented the field geology.Two wells at Wytch Farm field were studied. The results suggested that for one of the sampled wells, the model built using the spreadsheet random number generator gave the best match to the well test data. In the well, the permeability from the test interpretation matched the geometric average permeability. This average is the “correct” upscaled permeability for a random system, and this was consistent with the random nature of the geological model. For the second well investigated, a more complex “channel object” model appeared to fit the dynamic data better.All the models were built with stationary properties. However, the well test data suggested that some parts of the field have different statistical properties and hence show non‐stationarity. These differences would have to be built into the model representing the local geology.This study presents a workflow that is not yet considered standard in the oil industry, and the use of dynamic data to evaluate geological models requires further development. The study highlights the fact that the comparison or matching of results from reservoir models and well‐test analyses is not always straightforward in that different models may match different wells. The study emphasises the need for integrated analyses of geological and engineering data. The methods and procedures presented are intended to form a feedback loop which can be used to evaluate the representivity of a geological model.
OILS FROM CENOZOIC RIFT‐BASINS IN CENTRAL AND NORTHERN THAILAND: SOURCE AND THERMAL MATURITY
Authors: Petersen H.I. , Nytoft H.P. , Ratanasthien B. , Foopatthanakamol A. 
Published: January 2007

Oil is produced from the Suphan Buri, Phitsanulok and Fang Basins onshore central and northern Thailand. Most of the Cenozoic rift‐basins onshore Thailand are 2–4 km deep, but the Phitsanulok Basin is the deepest with a basin‐fill up to 8 km thick. In this basin, the Sirikit field produces ∼18,000–24,000 bbl/day of crude oil. In the Suphan Buri Basin, about 400 bbl/day of crude oil is produced from the U Thong and Sang Kajai fields. Approximately 800 bbl/day of crude oil is produced from the Fang field (Fang Basin), which in reality consists of a number of minor structures including Ban Thi, Pong Nok, San Sai, Nong Yao and Mae Soon. A total of eight oil samples were collected from these structures and from the Sirikit, U Thong and Sang Kajai fields. The oils were subjected to MPLC and HPLC separation and were analysed by gas chromatography (GC) and gas chromatography‐mass spectrometry (GC‐MS and GC‐MS‐MS). The U Thong oil was investigated in more detail by separating the oil into a number of fractions suited for the analysis of various specific compounds.The Sirikit oil appears to be the most mature, whereas the Suphan Buri oils and the oil from the San Sai structure (Fang Basin) are the least mature. Apart from the San Sai oil, the other oils in the Fang Basin are of similar maturity. The oils contain small amounts of asphaltenes and the asphaltene‐free fractions are completely dominated by saturated hydrocarbons (generally >60%). Long‐chain n‐alkanes extend to at least C40 and the oils are thus highly waxy. In general the oils were generated from freshwater lacustrine source rocks containing a large proportion of algal material, as indicated by the presence of long‐chain n‐alkanes, low C3122R/C30 hopane ratios, the presence of 28‐Nor‐spergulane, T26/T25 (tricyclic triterpanes) ratios of 1.07–1.57 and tetracyclic polyprenoid (TTP) ratios close to 1. Occasional saline conditions may have occurred during deposition of the Sirikit, Ban Thi and Pong Nok source rocks. The Fang Basin oils were sourced from two different kitchens, one feeding the Ban Thi and Pong Nok structures and one feeding the Mae Soon, Nong Yao and San Sai structures.The presence ofcadalene, tetracyclic C24 compounds, oleanane, lupane, bicadinane and trace amounts ofnorpimarane or norisopimarane indicate a contribution from higher land plant organic matter to the oils. The terrestrial organic matter may occur disseminated in the lacustrine facies or concentrated in coal seams associated with the lacustrine mudstones. Thermally immature oil shales (lacustrine mudstones) and coals exposed in numerous basins in central and northern Thailand could upon maturation generate oils with a composition comparable to the investigated oils.
Antigenic Divergence between
Bordetella pertussis
Clinical Isolates from Moscow, Russia, and Vaccine Strains
Authors: Borisova Olga , Kombarova Svetlana Yu , Zakharova Nelli S. , van Gent Marjolein , Aleshkin Vladimir A. , Mazurova Isabella , Mooi Frits R. 
Published: January 2007

ABSTRACT

We analyzed temporal changes in the frequencies of the
ptxA
,
prn
,
fim2
, and
fim3
alleles in
Bordetella pertussis
strains isolated from pertussis patients in Moscow, Russia, from 1948 to 2004. The three strains used for the whole-cell vaccine harbored the alleles
ptxA2
,
ptxA4
,
prn1
,
fim2-1
, and
fim3A
. Vaccine-type alleles of
ptxA
(
ptxA2
and
ptxA4
) were characteristic for all prevaccination strains and for 96% of the strains isolated in the 1960s and 1970s. At the beginning of the 1970s,
ptxA2
and
ptxA4
were replaced by the
ptxA1
allele. In the 1980s and to the present, strains with
ptxA1
were predominant in the
B. pertussis
population. All prevaccination strains harbored the
prn1
allele, which corresponds to the vaccine-type allele. In subsequent years, the proportion of strains with the
prn1
allele decreased and the proportion of
prn3
and
prn2
strains increased. From 2002 to 2004 strains with
prn2
or
prn3
were predominant in the
B. pertussis
population. The vaccine-type alleles
fim2-1
and
fim3A
were found in all prevaccination strains and in 92% of the strains isolated from 1960 to 1989. The
fim2-2
and
fim3B
alleles were first observed at the beginning of the 1980s. In subsequent years, these strains became predominant. Together with waning immunity, the antigenic divergence between vaccine strains and clinical isolates observed in the Moscow area may explain the persistence of pertussis, despite the high rates of vaccine coverage. The results demonstrate that the selection of
B. pertussis
strains for vaccine manufacturing must be based on a thorough study of the
B. pertussis
population.
Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice
Authors: Cortes-Perez Naima G. , Ah-Leung Sandrine , Bermúdez-Humarán Luis G. , Corthier Gérard , Wal Jean-Michel , Langella Philippe , Adel-Patient Karine 
Published: January 2007

ABSTRACTThe Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinantLactococcus lactisstrains expressing bovine β-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration ofL. lactisBLG and a second recombinantL. lactisstrain producing biologically active interleukin-12 (IL-12). ThisL. lactisstrain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermúdez-Humarán et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of bothL. lactisBLG and IL-12-producingL. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producingL. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with eitherL. lactisBLG orL. lactisBLG and IL-12-producingL. lactisinduces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated withL. lactisBLG andL. lactisBLG-IL-12-producingL. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the induction of a protective Th1 response by the association ofL. lactisBLG and IL-12-producingL. lactiswhich inhibits the elicitation of the allergic reaction to BLG in mice and (ii) the efficiency of intranasal administration of BLG for the induction of tolerance.
Natural Antibody and Complement Mediate Neutralization of Influenza Virus in the Absence of Prior Immunity
Authors: Jayasekera Jerome P. , Moseman E. Ashley , Carroll Michael C. 
Published: January 2007

ABSTRACTEarly control of virus replication by the innate immune response is essential to allow time for the generation of a more effective adaptive immune response. As an important component of innate immunity, complement has been shown to be necessary for protection against numerous microbial infections. This study was undertaken to investigate the role of complement in neutralizing influenza virus. Results demonstrated that the classical pathway of complement mediated serum neutralization of influenza virus. Although nonimmune serum neutralized influenza virus, the mechanism of virus neutralization (VN) required antibody, as sera from RAG1-deficient mice lacked VN activity; moreover, purified natural immunoglobulin M (IgM) restored VN activity to antibody-deficient sera. The mechanism of VN by natural IgM and complement was associated with virion aggregation and coating of the viral hemagglutinin receptor; however, viral lysis did not significantly contribute to VN. Additionally, reconstitution of RAG1-deficient mice with natural IgM resulted in delayed morbidity during influenza virus infection. Collectively, these results provide evidence that natural IgM and the early components of the classical pathway of complement work in concert to neutralize influenza virus and that this interaction may have a significant impact on the course of influenza viral pneumonia.
Efficient DNA Packaging of Bacteriophage PRD1 Requires the Unique Vertex Protein P6
Authors: Karhu Nelli J. , Ziedaite Gabija , Bamford Dennis H. , Bamford Jaana K. H. 
Published: January 2007

ABSTRACT
The assembly of bacteriophage PRD1 proceeds via formation of empty procapsids containing an internal lipid membrane, into which the linear double-stranded DNA genome is subsequently packaged. The packaging ATPase P9 and other putative packaging proteins have been shown to be located at a unique vertex of the PRD1 capsid. Here, we describe the isolation and characterization of a suppressor-sensitive PRD1 mutant deficient in the unique vertex protein P6. Protein P6 was found to be an essential part of the PRD1 packaging machinery; its absence leads to greatly reduced packaging efficiency. Lack of P6 was not found to affect particle assembly, because in the P6-deficient mutant infection, wild-type (wt) amounts of particles were produced, although most were empty. P6 was determined not to be a specificity factor, as the few filled particles seen in the P6-deficient infection contained only PRD1-specific DNA. The presence of P6 was not necessary for retention of DNA in the capsid once packaging had occurred, and P6-deficient DNA-containing particles were found to be stable and infectious, albeit not as infectious as wt PRD1 virions. A packaging model for bacteriophage PRD1, based on previous results and those obtained in this study, is presented.
Characterization of the Nuclear Export Signal in the Coronavirus Infectious Bronchitis Virus Nucleocapsid Protein
Authors: Reed Mark L. , Howell Gareth , Harrison Sally M. , Spencer Kelly-Anne , Hiscox Julian A. 
Published: January 2007

ABSTRACT
The nucleocapsid (N) protein of infectious bronchitis virus (IBV) localizes to the cytoplasm and nucleolus and contains an eight-amino-acid nucleolar retention motif. In this study, a leucine-rich nuclear export signal (NES) (291-LQLDGLHL-298) present in the C-terminal region of the IBV N protein was analyzed by using alanine substitution and deletion mutagenesis to investigate the relative contributions that leucine residues make to nuclear export and where these residues are located on the structure of the IBV N protein. The analysis indicated that Leu296 and Leu298 are required for efficient nuclear export of the protein. Structural information indicated that both of these amino acids are available for interaction with protein complexes involved in this process. However, export of N protein from the nucleus/nucleolus was not inhibited by leptomycin B treatment, indicating that N protein nuclear export is independent of the CRM1-mediated export pathway.
Impact of a traffic light nutrition tool in a primary school
Authors: Ellis Rona M , Ellis Robert C T 
Published: January 2007

Aims: To evaluate the impact of a school traffic light nutrition tool on the knowledge, attitude and behaviour of Key Stage 1 children (aged five to seven years). Methods: A school traffic light nutrition tool is created, adopting the principles advocated by the House of Commons Health Select Committee on Obesity, 1which seeks to encourage children to freely eat green food, eat amber food in moderation and stop and think before eating red food. A single sample pre-and post-test design is used to measure changes in children's knowledge, attitude and behaviour. A state primary school in the UK, located in an area of mixed private and social housing, with a non-selective admission policy is the setting for the study. In total 69 children, aged five to seven, were tested three weeks before and three weeks after nutrition education. Results: Knowledge improved significantly following nutrition education. Positive attitude scores and asking behaviour for red food decreased, but disappointingly positive feelings and asking behaviour for green food also diminished. Children's refusing behaviour for red food increased. Conclusion: Beneficial changes in knowledge, attitude and behaviour were observed, but negative changes in attitude scores and behaviour towards green food suggested that children misunderstood some nutritional messages. A lack of wider school involvement and only the partial support of parents weakened the effectiveness of this approach. The nutrition tool is cost neutral and may have applicability in other settings.