bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Responses Induced by Replication-Defective Adenovirus Expressing the C-Terminal Portion of theMycoplasma hyopneumoniaeP97 Adhesin
Authors: Okamba F. R. , Moreau E. , Cheikh Saad Bouh K. , Gagnon C. A. , Massie B. , Arella M. 
Published: April 2007

ABSTRACTMycoplasma hyopneumoniae, the causative agent of porcine enzootic pneumonia, colonizes the respiratory cilia of affected swine, causing significant economic losses to swine production worldwide. Vaccination is the most cost-effective strategy for the control and prevention of this disease. The goal of this study was to design and evaluate a replication-defective recombinant adenovirus, rAdP97c, expressing the C-terminal portion of P97 adhesin (P97c), an important pathogenesis-associated protein ofM. hyopneumoniae, as a new vaccine candidate againstM. hyopneumoniaeinfection. P97c-specific immune responses were evaluated in BALB/c mice following intranasal and intramuscular inoculation with rAdP97c. Mice inoculated by both routes of immunization produced significant levels of specific immunoglobulin G (IgG) antibodies in the serum and in bronchoalveolar lavage fluids (BALs). Animals immunized intranasally also produced a significant level of P97c-specific IgA in BALs. Intramuscular inoculation of rAdP97c induced a systemic and mucosal Th1-type biased response, evidenced by the predominance of IgG2a in the serum and BALs, whereas intranasal inoculation resulted in a mixed Th1/Th2-type response (balanced levels of IgG1 and IgG2a) in both sytemic and mucosal compartments. P97c-specific antibodies were able to inhibit the growth ofM. hyopneumoniaecells in vitro. These data suggest that rAdP97c vaccine may represent a new strategy for controlling infection byM. hyopneumoniae.
Serotype Distribution and Antimicrobial Susceptibilities of Nasopharyngeal Isolates of
Streptococcus pneumoniae
from Children Hospitalized for Acute Respiratory Illnesses in Hong Kong
Authors: Ip Margaret , Nelson E. Anthony S. , Cheuk Edmund S. C. , Sung Rita Y. T. , Li Albert , Ma Helen , Chan Paul K. S. 
Published: April 2007

ABSTRACT

Five hundred nineteen
Streptococcus pneumoniae
isolates from nasopharyngeal aspirates of 3,157 children (age, <16 years) participating in a respiratory surveillance study in Hong Kong in 2005 and 2006 indicated that 64.9% and 37.2% of the isolates were not susceptible to penicillin and cefotaxime, respectively. The rate of potential coverage by the seven-valent conjugate vaccine was 72.3%, and the rate increased to 74.6% for serogroup-specific types.
Base Pairing between
cis
-Acting Sequences Contributes to Template Switching during Plus-Strand DNA Synthesis in Human Hepatitis B Virus
Authors: Lewellyn Eric B. , Loeb Daniel D. 
Published: April 2007

ABSTRACT

Hepadnaviruses utilize two template switches (primer translocation and circularization) during synthesis of plus-strand DNA to generate a relaxed-circular (RC) DNA genome. In duck hepatitis B virus (DHBV) three
cis
-acting sequences, 3E, M, and 5E, contribute to both template switches through base pairing, 3E with the 3′ portion of M and 5E with the 5′ portion of M. Human hepatitis B virus (HBV) also contains multiple
cis
-acting sequences that contribute to the accumulation of RC DNA, but the mechanisms through which these sequences contribute were previously unknown. Three of the HBV
cis
-acting sequences (h3E, hM, and h5E) occupy positions equivalent to those of the DHBV 3E, M, and 5E. We present evidence that h3E and hM contribute to the synthesis of RC DNA through base pairing during both primer translocation and circularization. Mutations that disrupt predicted base pairing inhibit both template switches while mutations that restore the predicted base pairing restore function. Therefore, the h3E-hM base pairing appears to be a conserved requirement for template switching during plus-strand DNA synthesis of HBV and DHBV. Also, we show that base pairing is not sufficient to explain the mechanism of h3E and hM, as mutating sequences adjacent to the base pairing regions inhibited both template switches. Finally, we did not identify predicted base pairing between h5E and the hM region, indicating a possible difference between HBV and DHBV. The significance of these similarities and differences between HBV and DHBV will be discussed.
Herpes Simplex Virus Latency-Associated Transcript Sequence Downstream of the Promoter Influences Type-Specific Reactivation and Viral Neurotropism
Authors: Bertke Andrea S. , Patel Amita , Krause Philip R. 
Published: April 2007

ABSTRACT
Herpes simplex virus (HSV) establishes latency in sensory nerve ganglia during acute infection and may later periodically reactivate to cause recurrent disease. HSV type 1 (HSV-1) reactivates more efficiently than HSV-2 from trigeminal ganglia while HSV-2 reactivates more efficiently than HSV-1 from lumbosacral dorsal root ganglia (DRG) to cause recurrent orofacial and genital herpes, respectively. In a previous study, a chimeric HSV-2 that expressed the latency-associated transcript (LAT) from HSV-1 reactivated similarly to wild-type HSV-1, suggesting that the LAT influences the type-specific reactivation phenotype of HSV-2. To further define the LAT region essential for type-specific reactivation, we constructed additional chimeric HSV-2 viruses by replacing the HSV-2 LAT promoter (HSV2-LAT-P1) or 2.5 kb of the HSV-2 LAT sequence (HSV2-LAT-S1) with the corresponding regions from HSV-1. HSV2-LAT-S1 was impaired for reactivation in the guinea pig genital model, while its rescuant and HSV2-LAT-P1 reactivated with a wild-type HSV-2 phenotype. Moreover, recurrences of HSV-2-LAT-S1 were frequently fatal, in contrast to the relatively mild recurrences of the other viruses. During recurrences, HSV2-LAT-S1 DNA increased more in the sacral cord compared to its rescuant or HSV-2. Thus, the LAT sequence region, not the LAT promoter region, provides essential elements for type-specific reactivation of HSV-2 and also plays a role in viral neurotropism. HSV-1 DNA, as quantified by real-time PCR, was more abundant in the lumbar spinal cord, while HSV-2 DNA was more abundant in the sacral spinal cord, which may provide insights into the mechanism for type-specific reactivation and different patterns of central nervous system infection of HSV-1 and HSV-2.
The Kaposi's Sarcoma-Associated Herpesvirus K5 E3 Ubiquitin Ligase Modulates Targets by Multiple Molecular Mechanisms
Authors: Means Robert E. , Lang Sabine M. , Jung Jae U. 
Published: April 2007

ABSTRACT
Kaposi's sarcoma-associated herpesvirus encodes two highly related membrane-associated, RING-CH-containing (MARCH) family E3 ubiquitin ligases, K3 and K5, that can down regulate a variety of cell surface proteins through enhancement of their endocytosis and degradation. In this report we present data that while K5 modulation of major histocompatibility complex class I (MHC-I) closely mirrors the mechanisms used by K3, alternative molecular pathways are utilized by this E3 ligase in the down regulation of intercellular adhesion molecule 1 (ICAM-1) and B7.2. Internalization assays demonstrate that down regulation of each target can occur through increased endocytosis from the cell surface. However, mutation of a conserved tyrosine-based endocytosis motif in K5 resulted in a protein lacking the ability to direct an increased rate of MHC-I or ICAM-1 internalization but still able to down regulate B7.2 in a ubiquitin-dependent but endocytosis-independent manner. Further, mutation of two acidic clusters abolished K5-mediated MHC-I degradation while only slightly decreasing ICAM-1 or B7.2 protein destruction. This same mutant abolished detectable ubiquitylation of all targets. These data indicate that while K5 can act as an E3 ubiquitin ligase to directly mediate cell surface molecule destruction, regulation of its targets occurs through multiple pathways, including ubiquitin-independent mechanisms.
Location and Role of Free Cysteinyl Residues in the Sindbis Virus E1 and E2 Glycoproteins
Authors: Whitehurst Christopher B. , Soderblom Erik J. , West Michelle L. , Hernandez Raquel , Goshe Michael B. , Brown Dennis T. 
Published: April 2007

ABSTRACT
Sindbis virus is a single-stranded positive-sense RNA virus. It is composed of 240 copies of three structural proteins: E1, E2, and capsid. These proteins form a mature virus particle composed of two nested T=4 icosahedral shells. A complex network of disulfide bonds in the E1 and E2 glycoproteins is developed through a series of structural intermediates as virus maturation occurs (M. Mulvey and D. T. Brown, J. Virol. 68:805-812, 1994; M. Carleton et al., J. Virol. 71:1558-1566, 1997). To better understand the nature of this disulfide network, E1 and E2 cysteinyl residues were labeled with iodoacetamide in the native virus particle and analyzed by liquid chromatography-tandem mass spectrometry. This analysis identified cysteinyl residues of E1 and E2, which were found to be label accessible in the native virus particle, as well as those that were either label inaccessible or blocked by their involvement in disulfide bonds. Native virus particles alkylated with iodoacetamide demonstrated a 4-log decrease in viral infectivity. This suggests that the modification of free cysteinyl residues results in the loss of infectivity by destabilizing the virus particle or that a rearrangement of disulfide bonds, which is required for infectivity, is blocked by the modification. Although modification of these residues prevented infectivity, it did not alter the ability of virus to fuse cells after exposure to acidic pH; thus, modification of free cysteinyl residues biochemically separated the process of infection from the process of membrane fusion.
The effect of individual counselling and education on work ability and disability pension: a prospective intervention study in the construction industry
Authors: de Boer A G E M , Burdorf A , van Duivenbooden C , Frings-Dresen M H W 
Published: April 2007

Objectives:To investigate the effectiveness of a counselling and education programme on work ability and work disability pension for employees in the construction industry.Methods:Employees with a high disability risk of 38% or more in the following four years were included. Employees in the intervention group were either selected by an occupational physician or enrolled themselves. They received an assessment and individual programme focused on optimising work functioning, while the control group received care-as-usual. Data on work ability measured with the Work Ability Index (WAI) and work disability pensions were collected at baseline during a periodic occupational health examination and at 9, 18 and 26 months after the start of the intervention using a questionnaire.Results:Most employees in both the intervention (n = 83) and control group (n = 209) were carpenters (43% and 37%) and bricklayers (7% and 15%). In the intervention group, 42% successfully completed the programme. Work ability in the intervention group was lower at baseline but showed an increase over time while work ability of the control group remained the same. The work ability in the intervention group improved slightly more (p = 0.09). No statistically significant differences in percentages of employees receiving a disability pension between the intervention and control group were found at 9 or 18 months and no differences in the age-adjusted percentages of employees receiving a disability pension were found between the groups at any measurement.Conclusions:The programme was slightly effective in improving the work ability but not in reducing work disability pensions. A more comprehensive multidisciplinary intervention programme might be necessary.
NOISE MEASUREMENTS ON NbN THIN FILMS WITH A NEGATIVE TEMPERATURE RESISTANCE COEFFICIENT DEPOSITED ON SAPPHIRE AND ON SiO2
Authors: LEROY G. , GEST J. , VANDAMME L. K. J. , BOURGEOIS O. 
Published: April 2007

We characterize granular NbN x thin cermet films deposited on either sapphire substrate or on SiO 2 and compare the 1/f noise at 300 K and 80 K. The films were characterized with an impedance analyzer from 20 Hz to 1 MHz and analyzed as a resistor R in parallel with a capacitor C. The calculated noise voltage spectral density SvTh of the sample is in agreement with the experimentally observed noise for unbiased samples. The noise measurements on biased samples show 1/f noise. We checked that contact noise does not contribute to our measurements. The 1/f noise was compared for the films deposited on the silicon substrate and on the sapphire. Finally a model is proposed to explain the observed trends in the temperature resistance coefficient (TRC < 0 for all samples) and the relative 1/f noise at 300 K and 80 K with the composition x = N/Nb of the layers.
UNIX
TM
as an environment for producing numerical software
Authors: Schryer N. L. 
Published: April 2007

The UNIX operating system [1] supports a number of software tools which, when viewed as a whole, are an unusually powerful aid to programming.
The design, implementation, documentation and maintenance of a portable FORTRAN test of the floating-point arithmetic unit of a computer is used to illustrate these tools at work. The result of this effort was a program created automatically from the paper describing the test. Thus, only the documentation had to be written; the program was automatically produced from it. Also, changes in the document (debugging) were automatically reflected in the program.
The second section briefly describes the UNIX tools to be used. The third section outlines the basic problem and the fourth section shows how the tools can help solve the problem.
“Programming effort” analysis of the ELLPACK language
Authors: Rice John R. 
Published: April 2007

ELLPACK is a problem statement language and system for elliptic partial differential equations (PDEs) which is implemented by a Fortran preprocessor. ELLPACK's principal purpose is as a tool for the performance evaluation of software. However, we use it here as an example with which to study the “programming effort” required for problem solving. It is obvious that problem statement languages can reduce programming effort tremendously; our goal is to quantify this somewhat. We do this by analyzing the lengths and effort (as measured by Halstead's “software science” technique) of various approaches to solving these problems.
A simple ELLPACK program is shown below to illustrate the nature of the ELLPACK language. Space does not allow a description of the language but it is somewhat self explanatory. See [2] and [3] for further details.
Salmonella typhimurium Lacking Ribose Chemoreceptors Localize in Tumor Quiescence and Induce Apoptosis
Authors: Kasinskas Rachel W. , Forbes Neil S. 
Published: April 2007

Abstract
The effectiveness of most chemotherapeutics is limited by their inability to penetrate deep into tumor tissue and their ineffectiveness against quiescent cells. Motile Salmonella typhimurium, which are specifically attracted to compounds produced by quiescent cancer cells, could overcome this therapeutic barrier. We hypothesized that individual chemoreceptors target S. typhimurium to specific tumor microenvironments. To test this hypothesis, we used time-lapse fluorescent microscopy and tumor cylindroids to quantify the accumulation of chemotaxis machinery knockouts, including strains lacking individual cell surface chemoreceptors, chemotaxis signal transduction pathway enzymes, and the flagella and motor assemblies. To measure the extent of apoptosis induced by individual bacterial strains, caspase-3 activity was measured as a function of time. Our results showed how chemoreceptors directed bacterial chemotaxis within cylindroids: the aspartate receptor initiated chemotaxis toward cylindroids, the serine receptor initiated penetration, and the ribose/galactose receptor directed S. typhimurium toward necrosis. In addition, strains lacking proper flagella constructs, signal transduction proteins, or active motor function did not chemotax toward tumor cylindroids, indicating that directed chemotaxis is necessary to promote accumulation in tumors. By deleting the ribose/galactose receptor, bacterial accumulation localized to tumor quiescence and had a greater individual effect on inducing apoptosis than wild-type S. typhimurium. This new understanding of the mechanisms of Salmonella migration in tumors will allow for the development of bacterial therapies with improved targeting to therapeutically inaccessible regions of tumors. [Cancer Res 2007;67(7):3201–9]
Peroxisome Proliferator-Activated Receptor γ–Independent Suppression of Androgen Receptor Expression by Troglitazone Mechanism and Pharmacologic Exploitation
Authors: Yang Chih-Cheng , Wang Yu-Chieh , Wei Shuo , Lin Li-Fang , Chen Chang-Shi , Lee Cheng-Chun , Lin Cheng-Chieh , Chen Ching-Shih 
Published: April 2007

Abstract
Previously, we showed that the peroxisome proliferator-activated receptor γ (PPARγ) agonist troglitazone at high doses was able to suppress androgen receptor (AR) expression in LNCaP prostate cancer cells independently of PPARγ. Pharmacologic exploitation of this finding led to STG28, a PPARγ-inactive analogue of troglitazone with substantially higher potency in AR repression. Considering the pivotal role of AR in prostate tumorigenesis, this study investigates the mechanism by which troglitazone and derivatives suppress AR expression in LNCaP cells. Reverse transcription-PCR and reporter gene assays indicate that this drug-induced AR repression occurs at both mRNA and protein levels. Evidence suggests that troglitazone and derivatives mediate the transcriptional repression of AR by facilitating the ubiquitin-dependent proteasomal degradation of the transcriptional factor Sp1. These agents also cause the proteolysis of two proteins that regulate Sp1-mediated transcription (i.e., the TATA-binding protein–associated factor TAFII250 and cyclin D1). However, their involvement in the transcriptional repression of AR is refuted by the finding that small interfering RNA knockdown of these two regulatory proteins does not cause AR down-regulation. STG28 does not cause significant reduction in Sp1 or AR expression in normal prostate epithelial cells. This discriminatory effect underscores the differential susceptibility of malignant versus normal cells to the inhibitory effect of STG28 on cell viability. From a translational perspective, STG28 provides a proof of principle that potent AR-ablative agents could be developed through structural modifications of troglitazone. Moreover, as the control of Sp1 degradation remains unclear, STG28 represents a unique pharmacologic probe to investigate the ubiquitin-proteasome system that regulates Sp1 proteolysis. [Cancer Res 2007;67(7):3229–38]
Evidences that Leptin Up-regulates E-Cadherin Expression in Breast Cancer: Effects on Tumor Growth and Progression
Authors: Mauro Loredana , Catalano Stefania , Bossi Gianluca , Pellegrino Michele , Barone Ines , Morales Sara , Giordano Cinzia , Bartella Viviana , Casaburi Ivan , Andò Sebastiano 
Published: April 2007

Abstract
Leptin, a cytokine mainly produced by adipocytes, seems to play a crucial role in mammary carcinogenesis. In the present study, we explored the mechanism of leptin-mediated promotion of breast tumor growth using xenograft MCF-7 in 45-day-old female nude mice, and an in vitro model represented by MCF-7 three-dimensional cultures. Xenograft tumors, obtained only in animals with estradiol (E2) pellet implants, doubled control value after 13 weeks of leptin exposure. In three-dimensional cultures, leptin and/or E2 enhanced cell-cell adhesion. This increased aggregation seems to be dependent on E-cadherin because it was completely abrogated in the presence of function-blocking E-cadherin antibody or EGTA, a calcium-chelating agent. In three-dimensional cultures, leptin and/or E2 treatment significantly increased cell growth, which was abrogated when E-cadherin function was blocked. These findings well correlated with an increase of mRNA and protein content of E-cadherin in three-dimensional cultures and in xenografts. In MCF-7 cells both hormones were able to activate E-cadherin promoter. Mutagenesis studies, electrophoretic mobility shift assay, and chromatin immunoprecipitation assays revealed that cyclic AMP–responsive element binding protein and Sp1 motifs, present on E-cadherin promoter, were important for the up-regulatory effects induced by both hormones on E-cadherin expression in breast cancer MCF-7 cells. In conclusion, the present study shows how leptin is able to promote tumor cell proliferation and homotypic tumor cell adhesion via an increase of E-cadherin expression. This combined effect may give reasonable emphasis to the important role of this cytokine in stimulating primary breast tumor cell growth and progression, particularly in obese women. [Cancer Res 2007;67(7):3412–21]
Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin
Authors: Maloney Alison , Clarke Paul A. , Naaby-Hansen Soren , Stein Rob , Koopman Jens-Oliver , Akpan Akunna , Yang Alice , Zvelebil Marketa , Cramer Rainer , Stimson Lindsay , Aherne Wynne , Banerji Udai , Judson Ian , Sharp Swee , Powers Marissa , deBilly Emmanuel , Salmons Joanne , Walton Michael , Burlingame Al , Waterfield Michael , Workman Paul 
Published: April 2007

Abstract
The promising antitumor activity of 17-allylamino-17-demethoxygeldanamycin (17AAG) results from inhibition of the molecular chaperone heat shock protein 90 (HSP90) and subsequent degradation of multiple oncogenic client proteins. Gene expression microarray and proteomic analysis were used to profile molecular changes in the A2780 human ovarian cancer cell line treated with 17AAG. Comparison of results with an inactive analogue and an alternative HSP90 inhibitor radicicol indicated that increased expression of HSP72, HSC70, HSP27, HSP47, and HSP90β at the mRNA level were on-target effects of 17AAG. HSP27 protein levels were increased in tumor biopsies following treatment of patients with 17AAG. A group of MYC-regulated mRNAs was decreased by 17AAG. Of particular interest and novelty were changes in expression of chromatin-associated proteins. Expression of the heterochromatin protein 1 was increased, and expression of the histone acetyltransferase 1 and the histone arginine methyltransferase PRMT5 was decreased by 17AAG. PRMT5 was shown to be a novel HSP90-binding partner and potential client protein. Cellular protein acetylation was reduced by 17AAG, which was shown to have an antagonistic interaction on cell proliferation with the histone deacetylase inhibitor trichostatin A. This mRNA and protein expression analysis has provided new insights into the complex molecular pharmacology of 17AAG and suggested new genes and proteins that may be involved in response to the drug or be potential biomarkers of drug action. [Cancer Res 2007;67(7):3239–53]