bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential Integration of Adeno-Associated Virus Type 2 into a Polypyrimidine/Polypurine-Rich Region within
AAVS1
Authors: McAlister Victor J. , Owens Roland A. 
Published: July 2007

ABSTRACT

Adeno-associated virus type 2 (AAV2) preferentially integrates its genome into the
AAVS1
locus on human chromosome 19. Preferential integration requires the AAV2 Rep68 or Rep78 protein (Rep68/78), a Rep68/78 binding site (RBS), and a nicking site within
AAVS1
and may also require an RBS within the virus genome. To obtain further information that might help to elucidate the mechanism and preferred substrate configurations of preferential integration, we amplified junctions between AAV2 DNA and
AAVS1
from AAV2-infected HeLaJW cells and cells with defective Artemis or xeroderma pigmentosum group A genes. We sequenced 61 distinct junctions. The integration junction sequences show the three classical types of nonhomologous-end-joining joints: microhomology at junctions (57%), insertion of sequences that are not normally contiguous with either the AAV2 or the
AAVS1
sequences at the junction (31%), and direct joining (11%). These junctions were spread over 750 bases and were all downstream of the Rep68/78 nicking site within
AAVS1.
Two-thirds of the junctions map to 350 bases of
AAVS1
that are rich in polypyrimidine tracts on the nicked strand. The majority of AAV2 breakpoints were within the inverted terminal repeat (ITR) sequences, which contain RBSs. We never detected a complete ITR at a junction. Residual ITRs at junctions never contained more than one RBS, suggesting that the hairpin form, rather than the linear ITR, is the more frequent integration substrate. Our data are consistent with a model in which a cellular protein other than Artemis cleaves AAV2 hairpins to produce free ends for integration.
Minute Virus of Mice, a Parvovirus, in Complex with the Fab Fragment of a Neutralizing Monoclonal Antibody
Authors: Kaufmann Bärbel , López-Bueno Alberto , Mateu Mauricio G. , Chipman Paul R. , Nelson Christian D. S. , Parrish Colin R. , Almendral José M. , Rossmann Michael G. 
Published: July 2007

ABSTRACTThe structure of virus-like particles of the lymphotropic, immunosuppressive strain of minute virus of mice (MVMi) in complex with the neutralizing Fab fragment of the mouse monoclonal antibody (MAb) B7 was determined by cryo-electron microscopy to 7-Å resolution. The Fab molecule recognizes a conformational epitope at the vertex of a three-fold protrusion on the viral surface, thereby simultaneously engaging three symmetry-related viral proteins in binding. The location of the epitope close to the three-fold axis is consistent with the previous analysis of MVMi mutants able to escape from the B7 antibody. The binding site close to the symmetry axes sterically forbids the binding of more than one Fab molecule per spike. MAb as well as the Fab molecules inhibits the binding of the minute virus of mice (MVM) to permissive cells but can also neutralize MVM postattachment. This finding suggests that the interaction of B7 with three symmetry-related viral subunits at each spike hinders structural transitions in the viral capsid essential during viral entry.
Fatal Neurological Disease in Scrapie-Infected Mice Induced for Experimental Autoimmune Encephalomyelitis
Authors: Friedman-Levi Yael , Ovadia Haim , Hoftberger Romana , Einstein Ofira , Abramsky Oded , Budka Herbert , Gabizon Ruth 
Published: July 2007

ABSTRACT

During the years or decades of prion disease incubation, at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections, autoimmune diseases, or inflammatory processes. Whether prion disease incubation time and clinical signs or otherwise the pathology of intercurrent diseases can be affected by the coinfection process is unknown. To investigate this possibility, mice infected with the scrapie agent at both high and low titers were subsequently induced for experimental autoimmune encephalomyelitis, an immune system-mediated model of central nervous system (CNS) inflammation. We show here that coinduced mice died from a progressive neurological disease long before control mice succumbed to classical scrapie. To investigate the mechanism of the coinduced syndrome, we evaluated biochemical and pathological markers of both diseases. Brain and spleen PrP
Sc
levels in the dying coinduced mice were comparable to those observed in asymptomatic scrapie-infected animals, suggesting that coinduced disease is not an accelerated form of scrapie. In contrast, inflammatory markers, such as demyelination, immune cell infiltrates, and gliosis, were markedly increased in coinduced mouse spinal cords. Activated astrocytes were especially elevated in the medulla oblongata. Furthermore, PrP
sc
depositions were found in demyelinated white matter areas in coinduced mouse spinal cords, suggesting the presence of activated infected immune cells that infiltrate into the CNS to facilitate the process of prion neuroinvasion. We hypothesize that inflammatory processes affecting the CNS may have severe clinical implications in subjects incubating prion diseases.
Polyomavirus Small T Antigen Controls Viral Chromatin Modifications through Effects on Kinetics of Virus Growth and Cell Cycle Progression
Authors: Dahl Jean , Chen H. Isaac , George Michael , Benjamin Thomas L. 
Published: July 2007

ABSTRACTMinichromosomes of wild-type polyomavirus were previously shown to be highly acetylated on histones H3 and H4 compared either to bulk cell chromatin or to viral chromatin of nontransforminghr-tmutants, which are defective in both the small T and middle T antigens. A series of site-directed virus mutants have been used along with antibodies to sites of histone modifications to further investigate the state of viral chromatin and its dependence on the T antigens. Small T but not middle T was important in hyperacetylation at major sites in H3 and H4. Mutants blocked in middle T signaling pathways but encoding normal small T showed a hyperacetylated pattern similar to that of wild-type virus. The hyperacetylation defect ofhr-tmutant NG59 was partially complemented by growth of the mutant in cells expressing wild-type small T. In contrast to the hypoacetylated state of NG59, NG59 minichromosomes were hypermethylated at specific lysines in H3 and also showed a higher level of phosphorylation at H3ser10, a modification associated with the late G2and M phases of the cell cycle. Comparisons of virus growth kinetics and cell cycle progression in wild-type- and NG59-infected cells showed a correlation between the phase of the cell cycle at which virus assembly occurred and histone modifications in the progeny virus. Replication and assembly of wild-type virus were completed largely during S phase. Growth of NG59 was delayed by about 12 h with assembly occurring predominately in G2. These results suggest that small T affects modifications of viral chromatin by altering the temporal coordination of virus growth and the cell cycle.
Even Attenuated Bovine Leukemia Virus Proviruses Can Be Pathogenic in Sheep
Authors: Florins Arnaud , Gillet Nicolas , Boxus Mathieu , Kerkhofs Pierre , Kettmann Richard , Willems Luc 
Published: July 2007

ABSTRACT
Based on a reverse genetics approach, we previously reported that bovine leukemia virus (BLV) mutants harboring deletions in the accessory R3 and G4 genes persist at very low proviral loads and are unable to induce leukemia or lymphoma in sheep, indicating that these R3 and G4 gene sequences are required for pathogenesis. We now show that lymphoma can occur, albeit infrequently (1 case of 20) and after extended periods of latency (7 years). Direct sequencing and reinfection experiments demonstrated that lymphomagenesis was not due to the reversion of the mutant to the wild type. Similar observations with another type of attenuated mutant impaired in the transmembrane protein (TM) YXXL signaling motifs were made. We conclude that the R3 and G4 genes and the TM YXXL motifs are not strictly required for pathogenesis but that their integrity contributes to disease frequency and latency.
Bortezomib Induces Apoptosis of Epstein-Barr Virus (EBV)-Transformed B Cells and Prolongs Survival of Mice Inoculated with EBV-Transformed B Cells
Authors: Zou Ping , Kawada Junichi , Pesnicak Lesley , Cohen Jeffrey I. 
Published: July 2007

ABSTRACT
Bortezomib, an inhibitor of the 26S proteasome, is currently approved for treatment of multiple myeloma and is being studied for therapy of non-Hodgkin's lymphoma. We found that Epstein-Barr virus (EBV)-positive B cells with type III latency were more susceptible to killing by bortezomib than those with type I latency. Bortezomib induced apoptosis of EBV lymphoblastoid cell lines (LCLs) by inducing cleavage of caspases 8 and 9; apoptosis was inhibited by pretreatment with a pan-caspase inhibitor. Bortezomib reduced the levels of the p50 and p65 components of the canonical NF-κB pathway and reduced the level of p52 in the noncanonical NF-κB pathway, which is induced by EBV LMP1. Bortezomib inhibited expression of cIAP-1, cIAP-2, and XIAP, which are regulated by NF-κB and function as inhibitors of apoptosis. Bortezomib did not inhibit expression of several other antiapoptotic proteins, including Bcl-2 and Bcl-XL. Finally, bortezomib significantly prolonged the survival of severe combined immunodeficiency mice inoculated with LCLs. These findings suggest that bortezomib may represent a novel strategy for the treatment of certain EBV-associated lymphomas.
Echocardiographic assessment of blood flow volume in the superior vena cava and descending aorta in the newborn infant
Authors: Groves A M , Kuschel C A , Knight D B , Skinner J R 
Published: July 2007

Background:Clinical methods of assessing adequacy of the circulation are poor predictors of volume of blood flow in the newborn preterm. Doppler echocardiography can be used to assess perfusion at various sites in the circulation.Objective:To assess repeatability of measurement of volume of superior vena caval (SVC) and descending aortic (DAo) flow.Design:SVC and DAo flow volume were assessed four times in the first 48 h of postnatal life in a cohort of preterm (<31 weeks) infants. Within-observer and between-observer repeatability was assessed in a subgroup of preterm infants. Normative values were derived from 14 preterm infants who required <48 h respiratory support and 13 healthy term infants.Results:Within-observer repeatability coefficient was 30 ml/kg/min for quantification of SVC flow, and 2.2 cm for DAo stroke distance. Measurement of DAo diameter had poor repeatability. Between-observer repeatability appeared poorer than within-observer repeatability. The fifth centile for volume of SVC flow in healthy preterm infants was 55 ml/kg/min and 4.5 cm for DAo stroke distance.Conclusions:Echocardiographic assessments of volume of SVC flow and velocity of DAo flow have similar within-observer repeatability to other neonatal haemodynamic measurements. Between-observer repeatability for both measurements was poor, reflecting the difficulty of standardising these novel techniques. In this small cohort of preterm infants, SVC flow volume <55 ml/kg/min and DAo stroke distance <4.5 cm represented low or borderline systemic perfusion in the first 48 h of postnatal life.
Using administrative sickness absence data as a marker of future disability pension: the prospective DREAM study of Danish private sector employees
Authors: Lund Thomas , Kivimäki Mika , Labriola Merete , Villadsen Ebbe , Christensen Karl Bang 
Published: July 2007

Objectives:The aim of this study was to examine duration of sickness absence as a risk marker for future disability pension among all private sector employees in Denmark 1998–2004.Methods:All private sector employees receiving sickness absence compensation from the municipality in 1998, a total of 225 056 persons (39.2% women 61.8% men, age range 18–65, mean age 37.2), were followed in a national register to determine granted disability pension during the period 1 January 2001 through 31 December 2004. The authors excluded pensions in 1999 and 2000 to determine the status of sickness absence duration as an early risk marker.Results:5694 persons (2.5%) received disability pension during follow-up, more men (53.4%) than women (46.6%). There was a strong graded association between increasing length of absence and increasing risk of future disability pension. Significant differences were found between the younger and older age strata: men below 40 experiencing more than 26 weeks of sickness absence had a 16-fold risk of disability pension. The corresponding figure for men 40 years or older was approximately 7. For women, the corresponding figures were 12.6 and 6.7 respectively.Conclusion:The findings suggest that administratively collected data on sickness absence compensation are an important predictor of disability pension among private sector employees. The use of information on sick leave may improve the effectiveness of early interventions by policy makers, case managing authorities, employers and physicians.
Islamic Insurance: National Features and Legal Regulation
Authors: Bekkin Renat 
Published: July 2007

AbstractThe present paper studies Islamic insurance (takaful) as opposed to conventional one. The first part of the paper covers, among other things, such issues as nature and historic roots of Islamic insurance, early forms of Islamic insurance and narrates the disputes among Muslim scholars concerning the compatibility of insurance with Islamic Shariah. The second part deals with history and emergence of Islamic insurance in the modern financial market, as well as the practice of Islamic insurance in different countries. The third part discusses the feasibility of Islamic insurance in Russia in the current legal framework. The paper contains comprehensive glossary of related terms.
Chromosomal abnormalities in Philadelphia chromosome–negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase
Authors: Jabbour Elias , Kantarjian Hagop M. , Abruzzo Lynne V. , O'Brien Susan , Garcia-Manero Guillermo , Verstovsek Srdan , Shan Jianqin , Rios Mary Beth , Cortes Jorge 
Published: July 2007

Abstract
The development of chromosomal abnormalities (CAs) in the Philadelphia chromosome (Ph)–negative metaphases during imatinib (IM) therapy in patients with newly diagnosed chronic myecloid leukemia (CML) has been reported only anecdotally. We assessed the frequency and significance of this phenomenon among 258 patients with newly diagnosed CML in chronic phase receiving IM. After a median follow-up of 37 months, 21 (9%) patients developed 23 CAs in Ph-negative cells; excluding −Y, this incidence was 5%. Sixteen (70%) of all CAs were observed in 2 or more metaphases. The median time from start of IM to the appearance of CAs was 18 months. The most common CAs were −Y and + 8 in 9 and 3 patients, respectively. CAs were less frequent in young patients (P = .02) and those treated with high-dose IM (P = .03). In all but 3 patients, CAs were transient and disappeared after a median of 5 months. One patient developed acute myeloid leukemia (associated with − 7). At last follow-up, 3 patients died from transplantation-related complications, myocardial infarction, and progressive disease and 2 lost cytogenetic response. CAs occur in Ph-negative cells in a small percentage of patients with newly diagnosed CML treated with IM. In rare instances, these could reflect the emergence of a new malignant clone.
β3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea
Authors: Piérola J. , Barceló A. , de la Peña M. , Barbé F. , Soriano J. B. , Sánchez Armengol A. , Martínez C. , Agustí A. 
Published: July 2007

Obesity is an important risk factor for obstructive sleep apnoea syndrome (OSAS), insulin resistance and cardiovascular disease. The substitution of tryptophan 64 with arginine (Trp64Arg) polymorphism (Arg variant) of the β3-adrenergic receptor (ADRB3) has been associated with obesity. In this study, the prevalence of the Trp64Arg ADRB3 polymorphism in a large group of patients with OSAS and its association with body mass index (BMI), insulin resistance and hypertension were evaluated.ADRB3 genotype was determined in 387 patients with OSAS and 137 healthy subjects recruited from three Spanish tertiary hospitals.The distributions of the ADRB3 genotypes were similar in OSAS and controls, and, in a multivariate model, the risk of OSAS was not associated with the presence of the Arg variant of the ADRB3 gene. However, BMI was higher in those patients with OSAS who carried this genetic variant than in those with the Trp variant. Furthermore, a linear trend for higher BMI was found in those with the Arg variant (56, 75 and 100% for Trp/Trp, Trp/Arg and Arg/Arg, respectively). Insulin resistance, blood pressures and serum levels of lipids and glucose were not associated with the presence of the Arg variant of the ADRB3 gene.The presence of the arginine 64 allele of the β3-adrenergic receptor gene does not increase the risk of obstructive sleep apnoea syndrome, but is associated with the development of obesity in those patients who suffer obstructive sleep apnoea syndrome.
Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea
Authors: Beecroft J. M. , Hoffstein V. , Pierratos A. , Chan C. T. , McFarlane P. A. , Hanly P. J. 
Published: July 2007

Sleep apnoea is common in patients with end-stage renal disease (ESRD). It was hypothesised that this is related to a narrower upper airway. Upper airway dimensions in patients with and without ESRD and sleep apnoea were compared, in order to determine whether upper airway changes associated with ESRD could contribute to the development of sleep apnoea.An acoustic reflection technique was used to estimate pharyngeal cross-sectional area. Sleep apnoea was assessed by overnight polysomnography. A total of 44 patients with ESRD receiving conventional haemodialysis and 41 subjects with normal renal function were studied. ESRD and control groups were further categorised by the presence or absence of sleep apnoea (apnoea/hypopnoea index ≥10 events·h−1).The pharyngeal area was smaller in patients with ESRD compared with subjects with normal renal function: 3.04±0.84versus3.46±0.80 cm2for the functional residual capacity and 1.99±0.51versus2.14±0.58 cm2for the residual volume. The pharynx is narrower in patients with ESRD than in subjects with normal renal function.In conclusion, since a narrower upper airway predisposes to upper airway occlusion during sleep, it is suggested that this factor contributes to the pathogenesis of sleep apnoea in dialysis-dependent patients.
An analysis of expression patterns of genes encoding proteins with catalytic activities
Authors: Cankaya Murat , Hernandez Ana Martinez , Ciftci Mehmet , Beydemir Sukru , Ozdemir Hasan , Budak Harun , Gulcin Ilhami , Comakli Veysel , Emircupani Tufan , Ekinci Deniz , Kuzu Muslum , Jiang Qiuhong , Eichele Gregor , Kufrevioglu Omer Irfan 
Published: July 2007

Abstract

Background

In situ hybridization (ISH) is a powerful method for visualizing gene expression patterns at the organismal level with cellular resolution. When automated, it is capable of determining the expression of a large number of genes.

Results
The expression patterns of 662 genes that encode enzymes were determined by ISH in the mid-gestation mouse embryo, a stage that models the complexity of the adult organism. Forty-five percent of transcripts encoding metabolic enzymes (n = 297) showed a regional expression pattern. A similar percentage was found for the 190 kinases that were also analyzed. Many mRNAs encoding glycolytic and TCA cycle enzymes exhibited a characteristic expression pattern. The annotated expression patterns were deposited on the Genepaint database and are retrievable by user-defined queries including gene name and sites of expression.

Conclusion
The 662 expression patterns discussed here comprised gene products with activities associated with catalysis. Preliminary analysis of these data revealed that a significant number of genes encoding housekeeping functions such as biosynthesis and catabolism were expressed regionally, so they could be used as tissue-specific gene markers. We found no difference in tissue specificity between mRNAs encoding housekeeping functions and those encoding components of signal transduction pathways, as exemplified by the kinases.
The use of simple dynamic mucosal models and confocal microscopy for the evaluation of lyophilised nasal formulations
Authors: McInnes Fiona , Baillie Alan J , Stevens Howard N E 
Published: July 2007

Abstract
A range of methods is reported in the literature for assessing hydration and adhesion parameters in the performance of nasal bioadhesive formulations; however, these tests do not always represent the dynamic conditions in the nasal cavity. Lyophilised formulations intended for nasal administration were evaluated using in-vitro tests designed in an attempt to mimic relevant processes in the nasal cavity, and intended to discriminate between different formulations. Initial investigative studies using scanning electron microscopy revealed that the lyophilisate had a highly porous internal structure, expected to provide an ideal porous pathway for re-hydration. Vapour sorption analysis demonstrated substantial weight gain of the lyophilisates on exposure to 95% relative humidity, ranging from 38% to 66%. Agar was used as a synthetic mucosal model designed to provide a standardised quantity of water available for rehydration of the formulations in in-vitro tests. A dynamic adhesion test and a texture analyser sliding test were designed to quantify different aspects of the spreading and adhesion of the hydrating formulations on the synthetic mucosal surface. Examination of the lyophilised formulations using confocal microscopy allowed visualisation and quantification of the initial rate of water ingress into the lyophilisates, which was found to consist of an initial rapid phase, followed by a slower steady-state phase. The results demonstrated that the use of a combination of methods representing the dynamic conditions of the nasal cavity is advisable in order to evaluate a formulation fully and to avoid misleading conclusions.
Development of a robust once-a-day glipizide matrix system
Authors: Jamzad Shahla , Fassihi Reza 
Published: July 2007

Abstract
The robustness of a new hydroxypropylmethylcellulose (HPMC) based modified release glipizide (10 mg) formulation was studied. The tablet formulations were prepared by dry blending the ingredients and direct compression, incorporating a range of release modifying agents up to ± 20% w/w relative to an optimized formulation. The dissolution was assessed in 900 mL pH 6.8 buffer at 75 rev min−1 paddle speed. Calculated difference and similarity factors (f1 and f2) and results of analysis of variance suggest that the overall release profiles were similar. Compositional changes up to ± 20% w/w and a reduction of drug dose to half did not change the general release pattern of this low dose/pH-dependent drug in a significant way. It is concluded that the drug release from the developed matrix systems is highly dependent on the kinetics of hydration and erosion, and that the proposed compositional changes within ± 20% w/w did not alter this relationship. The particulate systems used were characterized by determining the Carr index, Hausner ratio and the rheological properties using a texture analyser. Results indicate that the release is reproducible and the system has potential for successful scale-up operation, while complying with recommended Food and Drug Administration guidelines “Scale Up and Post Approval Changes”.