bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Selection for Nucleotide Usage at Synonymous and Nonsynonymous Sites in Influenza A Virus Genes
Authors: Kryazhimskiy Sergey , Bazykin Georgii A. , Dushoff Jonathan 
Published: March 2008

ABSTRACT
Influenza A virus is one of the best-studied viruses and a model organism for the study of molecular evolution; in particular, much research has focused on detecting natural selection on influenza virus proteins. Here, we study the dynamics of the synonymous and nonsynonymous nucleotide composition of influenza A virus genes. In several genes, the nucleotide frequencies at synonymous positions drift away from the equilibria predicted from the synonymous substitution matrices. We investigate possible reasons for this unexpected behavior by fitting several regression models. Relaxation toward a mutation-selection equilibrium following a host jump fails to explain the dynamics of the synonymous nucleotide composition, even if we allow for slow temporal changes in the substitution matrix. Instead, we find that deep internal branches of the phylogeny show distinct patterns of nucleotide substitution and that these branches strongly influence the dynamics of nucleotide composition, suggesting that the observed trends are at least in part a result of natural selection acting on synonymous sites. Moreover, we find that the dynamics of the nucleotide composition at synonymous and nonsynonymous sites are highly correlated, providing evidence that even nonsynonymous sites can be influenced by selection pressure for nucleotide composition.
Murine Cytomegalovirus m38.5 Protein Inhibits Bax-Mediated Cell Death
Authors: Jurak Igor , Schumacher Uwe , Simic Hrvoje , Voigt Sebastian , Brune Wolfram 
Published: March 2008

ABSTRACT

Many viruses encode proteins that inhibit the induction of programmed cell death at the mitochondrial checkpoint. Murine cytomegalovirus (MCMV) encodes the m38.5 protein, which localizes to mitochondria and protects human HeLa cells and fibroblasts from apoptosis triggered by proteasome inhibitors but not from Fas-induced apoptosis. However, the ability of this protein to suppress the apoptosis of murine cells and its role during MCMV infection have not been investigated previously. Here we show that m38.5 is expressed at early time points during MCMV infection. Cells infected with MCMVs lacking m38.5 showed increased sensitivity to cell death induced by staurosporine, MG132, or the viral infection itself compared to the sensitivity of cells infected with wild-type MCMV. This defect was eliminated when an m38.5 or Bcl-X
L
gene was inserted into the genome of a deletion mutant. Using fibroblasts deficient in the proapoptotic Bcl-2 family proteins Bak and/or Bax, we further demonstrated that m38.5 protected from Bax- but not Bak-mediated apoptosis and interacted with Bax in infected cells. These results consolidate the role of m38.5 as a viral mitochondrion-localized inhibitor of apoptosis and its functional similarity to the human cytomegalovirus UL37x1 gene product. Although the m38.5 gene is not homologous to the UL37x1 gene at the sequence level, m38.5 is conserved among rodent cytomegaloviruses. Moreover, the fact that MCMV-infected cells are protected from both Bak- and Bax-mediated cell death suggests that MCMV possesses an additional, as-yet-unidentified mechanism to block Bak-mediated apoptosis.
NEDD4L Overexpression Rescues the Release and Infectivity of Human Immunodeficiency Virus Type 1 Constructs Lacking PTAP and YPXL Late Domains
Authors: Chung Hyo-Young , Morita Eiji , von Schwedler Uta , Müller Barbara , Kräusslich Hans-Georg , Sundquist Wesley I. 
Published: March 2008

ABSTRACT

The cellular ESCRT pathway functions in membrane remodeling events that accompany endosomal protein sorting, cytokinesis, and enveloped RNA virus budding. In the last case, short sequence motifs (termed late domains) within human immunodeficiency virus type 1 (HIV-1) p6
Gag
bind and recruit two ESCRT pathway proteins, TSG101 and ALIX, to facilitate virus budding. We now report that overexpression of the HECT ubiquitin E3 ligase, NEDD4L/NEDD4-2, stimulated the release of HIV-1 constructs that lacked TSG101- and ALIX-binding late domains, increasing infectious titers >20-fold. Furthermore, depletion of endogenous NEDD4L inhibited the release of these crippled viruses and led to cytokinesis defects. Stimulation of virus budding was dependent upon the ubiquitin ligase activity of NEDD4L and required only the minimal HIV-1 Gag assembly regions, demonstrating that Gag has ubiquitin-dependent,
cis
-acting late domain activities located outside of the p6 region. NEDD4L stimulation also required TSG101 and resulted in ubiquitylation of several ESCRT-I subunits, including TSG101. Finally, we found that TSG101/ESCRT-I was required for efficient release of Mason-Pfizer monkey virus, which buds primarily by using a PPXY late domain to recruit NEDD4-like proteins. These observations suggest that NEDD4L and possibly other NEDD4-like proteins can ubiquitylate and activate ESCRT-I to function in virus budding.
Efficient and Specific Rescue of Human Immunodeficiency Virus Type 1 Budding Defects by a Nedd4-Like Ubiquitin Ligase
Authors: Usami Yoshiko , Popov Sergei , Popova Elena , Göttlinger Heinrich G. 
Published: March 2008

ABSTRACT

To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPx
n
L late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.
AN ANALYTICAL APPROACH TO THE SAFETY OF ROAD NETWORKS
Authors: ZIO ENRICO , SANSAVINI GIOVANNI , MAJA ROBERTO , MARCHIONNI GIOVANNA 
Published: March 2008

In this paper, recently introduced topological measures of interconnection and efficiency of network systems are applied to the safety analysis of the road transport system of the Province of Piacenza in Italy.The vulnerability of the network is evaluated with respect to the loss of a road link, e.g. due to a car accident, road work or other jamming occurrences. Eventually, the improvement in the global and local safety indicators following the implementation of a road development plan is evaluated.
Regional Analysis of Trend and Step Changes Observed in Hydroclimatic Variables around the Colorado River Basin
Authors: Miller W. Paul , Piechota Thomas C. 
Published: March 2008

Abstract
Recent research has suggested that changes in temperature and precipitation events due to climate change have had a significant impact on the availability and timing of streamflow. In this study, monthly temperature and precipitation data collected over 29 climate divisions covering the entire Colorado River basin and monthly natural flow data from 29 U.S. Geological Survey (USGS) gauge locations along the Colorado River are investigated for trend or step changes using parametric and nonparametric statistical tests. Temperature increases are persistent (at least 10 climate divisions over 6 months in trend analysis) throughout the year over the Colorado River basin, whereas precipitation only notably increased over 17 climate divisions (during trend analysis) during February and remained relatively unchanged otherwise. These results correspond with changes in naturalized streamflow throughout the year. Streamflow increases are recorded between November and February but exhibit a decreasing trend over the traditional peak runoff season (April through July). Under trend analysis, 18 flow stations exhibited increasing trends in January and 19 flow stations exhibited decreasing trends in June. It is likely that increasing temperature trends have affected the character of precipitation in the Colorado River basin, causing a change in the timing of runoff events.
The Optimal Bulk Wind Differential Depth and the Utility of the Upper-Tropospheric Storm-Relative Flow for Forecasting Supercells
Authors: Houston Adam L. , Thompson Richard L. , Edwards Roger 
Published: March 2008

Abstract
An analysis of 4 yr of Rapid Update Cycle-2 (RUC-2) derived soundings in proximity to radar-observed supercells and nonsupercells is conducted in an effort to answer two questions: 1) over what depth is the fixed-layer bulk wind differential (BWD; the vector difference between the wind velocity at a given level and the wind velocity at the surface) the best discriminator between supercell and nonsupercell environments and 2) does the upper-tropospheric storm-relative flow (UTSRF) discriminate between the environments of supercells and nonsupercells? Previous climatologies of sounding-based supercell forecast parameters have documented the ability of the 0–6-km BWD in delineating supercell from nonsupercell environments. However, a systematic examination of a wide range of layers has never been documented. The UTSRF has previously been tested as a parameter for discriminating between supercell and nonsupercell environments and there is some evidence that supercells may be sensitive to the UTSRF. However, this sensitivity may be a consequence of the correlation between UTSRF and the surface to midtropospheric BWD. Accurately assessing the ability of the UTSRF to distinguish between supercell and nonsupercell environments requires controlling for the surface to midtropospheric BWD.
It is shown that the bulk wind differential within the 0–5-km layer delineates best between supercell and nonsupercell environments. Analysis of the UTSRF demonstrates that even when not controlling for the BWD, the UTSRF has limited reliability in forecasting supercells. The lack of merit in using the UTSRF to forecast supercells is particularly evident when it is isolated from the BWD. Because the UTSRF and BWD are not independent, controlling for the BWD when examining the UTSRF reveals that the UTSRF is not a fundamental parameter that can be used to distinguish supercell from nonsupercell environments. Therefore, this work demonstrates that the UTSRF is an unreliable metric for forecasting supercell events.
Mycobacterium aviumcomplex disease: prognostic implication of high-resolution computed tomography findings
Authors: Kuroishi S. , Nakamura Y. , Hayakawa H. , Shirai M. , Nakano Y. , Yasuda K. , Suda T. , Nakamura H. , Chida K. 
Published: March 2008

To evaluate the prognostic implications of computed tomography (CT) findings in assessing responses to treatment inMycobacterium aviumcomplex (MAC) pulmonary disease without underlying lung disease, high-resolution (HR)CT findings were correlated based on the results of sputum conversion after anti-MAC therapy.A total of 59 patients underwent HRCT before treatment and the therapeutic efficacy was evaluated by the results of sputum conversion.Atelectasis, cavities and pleural thickening on HRCT were significantly more frequent and extensive among patients in the sputum nonconverted group than among those in the converted group. Furthermore, bronchiectasis was also significantly more extensive among patients in the nonconverted group, even though there was no significant difference in frequency between these two groups.These results suggest that high-resolution computed tomography findings are good predictors of response to treatment inMycobacterium aviumcomplex pulmonary disease.
C-reactive protein, obesity, atopy and asthma symptoms in middle-aged adults
Authors: Butland B. K. , Strachan D. P. , Rudnicka A. R. 
Published: March 2008

Recent research has suggested an association between circulating C-reactive protein (CRP) and adult asthma, confined to those without evidence of allergic predisposition. The current authors investigated the role of smoking and obesity as possible explanations for this relationship.At 44–45 yrs of age, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of the following: CRP; the specific immunoglobulin E to grass, cat and dust mite; standing height; and weight. Information on asthma and related symptoms was collected by computer-aided interview when the subjects were 42 yrs of age. Complete data were available for a total of 6,490 subjects.CRP levels were positively correlated with the body mass index (BMI) and were found to be higher among females when compared with males, and higher among heavy smokers (≥20 cigarettes·day−1) when compared with never-smokers. After adjustment for sex and region, the odds ratios, comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first quartile, were 1.85 (95% confidence interval 1.15–2.99) for nonatopics and 0.94 (0.62–1.41) for atopics, changing to 1.36 (0.80–2.32) and 1.07 (0.67–1.69), respectively, when additionally adjusted for smoking and BMI.Any association between C-reactive protein and asthma prevalence confined to nonatopics may be due to confounding factors. Alternatively, it may reflect a more general association of C-reactive protein with smoking-related obstructive airways disease.
Modulation of bleomycin-induced lung fibrosis by serotonin receptor antagonists in mice
Authors: Fabre A. , Marchal-Sommé J. , Marchand-Adam S. , Quesnel C. , Borie R. , Dehoux M. , Ruffié C. , Callebert J. , Launay J-M. , Hénin D. , Soler P. , Crestani B. 
Published: March 2008

Serotonin (5-hydroxytryptamine; 5-HT) is known to increase proliferation and collagen synthesis by fibroblasts. Two receptor subtypes, 5-HT2A and 5-HT2B, have been shown to play the most important roles in the lung.In the present study, the role of serotonin in lung fibrosis was investigated using the bleomycin mouse model.Serotonin concentrations in lung homogenates increased significantly over the time course of bleomycin-induced fibrosis, with a maximum at day seven. The expression of serotonin receptors 5-HT2A and 5-HT2B increased in the lung after bleomycin treatment, as assessed by PCR, specific binding and immunohistochemistry. Blockage of 5-HT2A receptors by ketanserin and 5-HT2B receptors by SB215505 reduced bleomycin-induced lung fibrosis, as demonstrated by reduced lung collagen content and reduced procollagen 1 and procollagen 3 mRNA expression. Serotonin antagonists promoted an antifibrotic environment by decreasing the lung mRNA levels of transforming growth factor-β1, connective growth factor and plasminogen activator inhibitor-1 mRNA, but had minimal effects on lung inflammation as assessed by bronchoalveolar lavage cytology analysis. Interestingly, the 5-HT2B receptor was strongly expressed by fibroblasts in the fibroblastic foci in human idiopathic pulmonary fibrosis samples.In conclusion, the present study showed involvement of serotonin in the pathophysiology of bleomycin-induced lung fibrosis in mice and identified it as a potential therapeutic target in lung fibrotic disorders.
Effects of inhaled human insulin on airway lining fluid composition in adults with diabetes
Authors: Liu M. C. , Riese R. J. , Van Gundy K. , Norwood P. , Sullivan B. E. , Schwartz P. F. , Teeter J. G. 
Published: March 2008

Inhaled human insulin (Exubera® (human insulin of rDNA origin) Inhalation Powder) causes small, early and reversible changes in pulmonary function in subjects with diabetes mellitus. The present study assessed whether changes occur in cellular and soluble constituents of airway lining fluid consistent with inflammation as a possible cause for Exubera®-associated lung function alterations.Two 31-week, open-label, sequential design phase 2 studies were conducted, one with 20 subjects with type 1 and one with 24 subjects with type 2 diabetes. After run-in, all subjects received subcutaneous insulin for 12 weeks, followed after 1 week by 12 weeks of Exubera®. Bronchoalveolar lavage fluid cell counts and protein constituents were determined at baseline, after 12 weeks of subcutaneous insulin and after 12 weeks of Exubera®.Baseline cellular and soluble constituents of lavage fluid were similar to those reported for nondiabetic adults. Exubera® produced no consistent clinically or statistically significant changes in total or differential lavage fluid cell counts or protein concentrations, even though Exubera®-associated changes in pulmonary function are known to be fully manifest within 12 weeks.Therefore, 12 weeks of Exubera® treatment is not associated with evidence of pulmonary inflammation. The treatment effects on lung function observed in Exubera® trials are not caused by lung inflammation.
Leukotriene B4: early mediator of atherosclerosis in obstructive sleep apnoea?
Authors: Lefebvre B. , Pépin J-L. , Baguet J-P. , Tamisier R. , Roustit M. , Riedweg K. , Bessard G. , Lévy P. , Stanke-Labesque F. 
Published: March 2008

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B4is a lipid mediator involved in atherogenesis.In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB4production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB4production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB4production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB4production, which was measured by liquid chromatography–tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls.LTB4production was increased in OSA patients compared with controls. LTB4levels correlated with the mean and minimal arterial oxygen saturation (Sa,O2). LTB4production correlated with luminal diameter data in patients with a meanSa,O2of ≤94% but not with IMT. Lastly, CPAP significantly reduced LTB4production by 50%.Leukotriene B4production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B4could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.
Clock gene dysfunction in patients with obstructive sleep apnoea syndrome
Authors: Burioka N. , Koyanagi S. , Endo M. , Takata M. , Fukuoka Y. , Miyata M. , Takeda K. , Chikumi H. , Ohdo S. , Shimizu E. 
Published: March 2008

Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes can contribute to various disorders. To investigate whether obstructive sleep apnoea syndrome (OSAS) influences clock gene function, the present authors examinedPeriod1(Per1) mRNA expressionin vitroandin vivo.In eight healthy subjects and eight OSAS patients, plasma noradrenaline, serum interleukin (IL)-6, high-sensitivity C-reactive protein (hsCRP) andPer1mRNA expression in peripheral whole blood were measured. Expression ofPer1mRNA in cultured cells was examined under IL-6 or noradrenaline stimulationin vitro. After noradrenaline was administered to micein vivo,Per1mRNA expression in the brain was examined.The concentrations of serum IL-6, hsCRP and plasma noradrenaline were elevated in OSAS patients, but improved by continuous positive airway pressure (CPAP) therapy.Per1mRNA expression in the peripheral blood significantly decreased at 02:00 h by CPAP in OSAS patients. Stimulation with IL-6 did not directly inducePer1mRNAin vitro. Administration of noradrenaline inducedPer1mRNA in the cerebral cortex of micein vivo.The current study revealed that obstructive sleep apnoea syndrome caused clock gene dysfunction, and continuous positive airway pressure helped to improve it. Sympathetic activation and elevation of the plasma noradrenaline concentration in obstructive sleep apnoea syndrome may be one of the factors involved in disorders ofPeriod1mRNA expression.
The association between serum osmolality and lung function among adults
Authors: Pogson Z. E. K. , McKeever T. M. , Fogarty A. 
Published: March 2008

The extensive pulmonary vasculature results in the lungs being intimately exposed to circulating blood. As increased serum osmolality may be associated with an increase in pro-inflammatory activity, this has the potential to result in damage to the lungs and reduced lung function. The objective of the present study was to test the hypothesis that increased serum osmolality is associated with a lower forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).The present study was a cross-sectional study of 10,602 participants in the Third National Health and Nutrition Examination Survey aged ≥17 yrs for whom there were adequate data on all outcomes and exposures.After adjustment for age, smoking and other confounding factors, increased serum osmolality was inversely associated with both FEV1and FVC. An increase of 1 sdin serum osmolality was associated with a decrease in both FEV1of 19.8 mL and FVC of 35.3 mL. The constituent assays demonstrated a complex relationship with both FEV1and FVC.Increased serum osmolality was associated with decreased forced expiratory volume in one second and forced vital capacity. If causal, this may have implications for the understanding of the processes that are involved in the pathophysiology of decline in lung function.
Sex differences in physiological progression of idiopathic pulmonary fibrosis
Authors: Han M. K. , Murray S. , Fell C. D. , Flaherty K. R. , Toews G. B. , Myers J. , Colby T. V. , Travis W. D. , Kazerooni E. A. , Gross B. H. , Martinez F. J. 
Published: March 2008

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for malesversusfemales.Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences.Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity.These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.