bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of c-FLIP and survivin down-regulation in flexible heteroarotinoid-induced apoptosis and enhancement of TRAIL-initiated apoptosis in lung cancer cells
Authors: Lin Yidan , Liu Xiangguo , Yue Ping , Benbrook Doris M. , Berlin K. Darrell , Khuri Fadlo R. , Sun Shi-Yong 
Published: November 2008

Abstract
The flexible heteroarotinoid, SHetA2, is a novel compound with apoptosis-inducing and anticancer activities in vitro and in vivo. Our previous research showed that up-regulation of death receptor 5 plays a critical role in the mechanism of SHetA2-induced apoptosis in human lung cancer cells. The hypothesis of this study was that the mechanism of SHetA2-induced apoptosis requires modulation of additional proteins critical for regulation of apoptosis, including cellular FLICE-inhibitory protein (c-FLIP), survivin, X-linked inhibitor of apoptosis, Bcl-2, Bcl-XL, Bax, and Bim. Western blot analysis showed that c-FLIP and survivin were substantially reduced in all of the tested cell lines exposed to SHetA2 compared with other proteins that were reduced only in a subset of the cell lines tested. Strikingly, overexpression of c-FLIP, but not survivin, protected cells from SHetA2-induced apoptosis and enhancement of TRAIL-initiated apoptosis, although knockdown of endogenous survivin did slightly sensitize cells to SHetA2-induced apoptosis. Consistent with these results, small interfering RNA-mediated reduction of c-FLIP was more effective than survivin down-regulation in triggering apoptosis in these cell lines. SHetA2 increased ubiquitination of c-FLIP and the consequent degradation was abrogated by the proteasome inhibitor MG132. Although SHetA2 treatment led to increased c-Jun phosphorylation, the JNK inhibitor SP600125 did not prevent c-FLIP down-regulation by SHetA2. Thus, it appears that SHetA2 down-regulates c-FLIP levels by facilitating its ubiquitin/proteasome-mediated degradation independent of JNK activation. Collectively, the present study indicates that, in addition to death receptor 5 up-regulation, c-FLIP down-regulation is another important component of flexible heteroarotinoid (SHetA2)-induced apoptosis as well as enhancement of TRAIL-induced apoptosis. [Mol Cancer Ther 2008;7(11):1–10] [Mol Cancer Ther 2008;7(11):3556–65]
Gene silencing for epidermal growth factor receptor variant III induces cell-specific cytotoxicity
Authors: Yamoutpour Farnaz , Bodempudi Vidya , Park Shay E. , Pan Weihong , Mauzy Mary Jean , Kratzke Robert A. , Dudek Arkadiusz , Potter David A. , Woo Richard A. , O'Rourke Donald M. , Tindall Donald J. , Farassati Faris 
Published: November 2008

Abstract
Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively active mutant form of EGFR that is expressed in 40% to 50% of gliomas and several other malignancies. Here, we describe the therapeutic effects of silencing EGFRvIII on glioma cell lines in vitro and in vivo. A small interfering RNA molecule against EGFRvIII was introduced into EGFRvIII-expressing glioma cells (U87Δ) by electroporation resulting in complete inhibition of expression of EGFRvIII as early as 48 h post-treatment. During EGFRvIII silencing, a decrease in the proliferation and invasiveness of U87Δ cells was accompanied by an increase in apoptosis (P &lt; 0.05). Notably, EGFRvIII silencing inhibited the signal transduction machinery downstream of EGFRvIII as evidenced by decreases in the activated levels of Ras and extracellular signal-regulated kinase. A lentivirus capable of expressing anti-EGFRvIII short hairpin RNA was also able to achieve progressive silencing of EGFRvIII in U87Δ cells in addition to inhibiting cell proliferation, invasiveness, and colony formation in a significant manner (P &lt; 0.05). Silencing EGFRvIII in U87Δ cultures with this virus reduced the expression of factors involved in epithelial-mesenchymal transition including N-cadherin, β-catenin, Snail, Slug, and paxillin but not E-cadherin. The anti-EGFRvIII lentivirus also affected the cell cycle progression of U87Δ cells with a decrease in G1 and increase in S and G2 fractions. In an in vivo model, tumor growth was completely inhibited in severe combined immunodeficient mice (n = 10) injected s.c. with U87Δ cells treated with the anti-EGFRvIII lentivirus (P = 0.005). We conclude that gene specific silencing of EGFRvIII is a promising strategy for treating cancers that contain this mutated receptor. [Mol Cancer Ther 2008;7(11):3586–97]
Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors
Authors: Ross-Macdonald Petra , de Silva Heshani , Guo Qi , Xiao Hong , Hung Chen-Yi , Penhallow Becky , Markwalder Jay , He Liqi , Attar Ricardo M. , Lin Tai-an , Seitz Steven , Tilford Charles , Wardwell-Swanson Judith , Jackson Donald 
Published: November 2008

Abstract
In developing inhibitors of the LIM kinases, the initial lead molecules combined potent target inhibition with potent cytotoxic activity. However, as subsequent compounds were evaluated, the cytotoxic activity separated from inhibition of LIM kinases. A rapid determination of the cytotoxic mechanism and its molecular target was enabled by integrating data from two robust core technologies. High-content assays and gene expression profiling both indicated an effect on microtubule stability. Although the cytotoxic compounds are still kinase inhibitors, and their structures did not predict tubulin as an obvious target, these results provided the impetus to test their effects on microtubule polymerization directly. Unexpectedly, we confirmed tubulin itself as a molecular target of the cytotoxic kinase inhibitor compounds. This general approach to mechanism of action questions could be extended to larger data sets of quantified phenotypic and gene expression data. [Mol Cancer Ther 2008;7(11):3490–8]
Influence of Cloud Condensation Nuclei on Orographic Snowfall
Authors: Saleeby Stephen M. , Cotton William R. , Lowenthal Douglas , Borys Randolph D. , Wetzel Melanie A. 
Published: November 2008

Abstract
Pollution aerosols acting as cloud condensation nuclei (CCN) have the potential to alter warm rain clouds via the aerosol first and second indirect effects in which they modify the cloud droplet population, cloud lifetime and size, rainfall efficiency, and radiation balance from increased albedo. For constant liquid water content, an increase in CCN concentration (NCCN) tends to produce an increased concentration of droplets with smaller diameters. This reduces the collision and coalescence rate, and thus there is a local reduction in rainfall. While this process applies to warm clouds, it does not identically carry over to mixed-phase clouds in which crystal nucleation, crystal riming, crystal versus droplet fall speed, and collection efficiency play active roles in determining precipitation amount. Sulfate-based aerosols serve as very efficient cloud nuclei but are not effective as ice-forming nuclei. In clouds where precipitation formation is dominated by the ice phase, NCCN influences precipitation growth by altering the efficiency of droplet collection by ice crystals and the fall trajectories of both droplet and crystal hydrometeors. The temporal and spatial variation in both crystal and droplet populations determines the resultant snowfall efficiency and distribution. Results of numerical simulations in this study suggest that CCN can play a significant role in snowfall production by winter, mixed-phase, cloud systems when liquid and ice hydrometeors coexist. In subfreezing conditions, a precipitating ice cloud overlaying a supercooled liquid water cloud allows growth of precipitation particles via the seeder–feeder process, in which nucleated ice crystals fall through the supercooled liquid water cloud and collect droplets. Enhanced NCCN from sulfate pollution by fossil fuel emissions modifies the droplet distribution and reduces crystal riming efficiency. Reduced riming efficiency inhibits the rate of snow growth, producing lightly rimed snow crystals that fall slowly and advect farther downstream prior to surface deposition. Simulations indicate that increasing NCCN along the orographic barrier of the Park Range in north-central Colorado results in a modification of the orographic cloud such that the surface snow water equivalent amounts are reduced on the windward slopes and enhanced on the leeward slopes. The inhibition of snowfall by pollution aerosols (ISPA) effect has significant implications for water resource distribution in mountainous terrain.
Generation and Propagation of Inertia–Gravity Waves from Vortex Dipoles and Jets
Authors: Wang Shuguang , Zhang Fuqing , Snyder Chris 
Published: November 2008

Abstract
This study investigates gravity wave generation and propagation from jets within idealized vortex dipoles using a nonhydrostatic mesoscale model. Two types of initially balanced and localized jets induced by vortex dipoles are examined here. These jets have their maximum strength either at the surface or in the middle levels of a uniformly stratified atmosphere. Within these dipoles, inertia–gravity waves with intrinsic frequencies 1–2 times the Coriolis parameter are simulated in the jet exit region. These gravity waves are nearly phase locked with the jets as shown in previous studies, suggesting spontaneous emission of the waves by the localized jets. A ray tracing technique is further employed to investigate the propagation effects of gravity waves. The ray tracing analysis reveals strong variation of wave characteristics along ray paths due to variations (particularly horizontal variations) in the propagating environment.
The dependence of wave amplitude on the jet strength (and thus on the Rossby number of the flow) is examined through experiments in which the two vortices are initially separated by a large distance but subsequently approach each other and form a vortex dipole with an associated amplifying localized jet. The amplitude of the stationary gravity waves in the simulations with 90-km grid spacing increases as the square of the Rossby number (Ro), when Ro falls in a small range of 0.05–0.15, but does so significantly more rapidly when a smaller grid spacing is used.
An Intercomparison of Observational, Reanalysis, Satellite, and Coupled Model Data on Mean Rainfall in the Caribbean
Authors: Jury Mark R. 
Published: November 2008

Abstract
This study examines the spatial variability of mean annual rainfall in the Caribbean in the satellite era 1979–2000. Intercomparisons of gridded rainfall fields from conventional stations, satellite estimators, reanalysis products, and coupled general circulation models (CGCMs) are made, with a focus on the Antilles island chain and their land–sea transitions. The rainfall products are rated for their ability to capture a number of key features, including (i) topographically enhanced precipitation over the larger western Antilles islands of Cuba, Jamaica, Hispanola, and Puerto Rico; (ii) the rain shadow west of Hispanola; (iii) the two dry zones where SSTs are low: north of Venezuela and north of the Lesser Antilles; and (iv) the wet axis extending north of Trinidad. The various monitoring and modeling systems produce gridded rainfall fields at resolutions from 50 to 280 km, from station reconstructions, satellite estimates, blended and reanalysis products, and CGCM climatologies with respect to surface forcing fields. Wet and dry biases were found in many of the reanalysis and satellite products, respectively—either over the whole Caribbean or in a certain sector. The intercomparison found some measure of consensus, but no single product is without discrepancy. High-resolution passive microwave satellite rainfall estimates [Climate Prediction Center’s multisaltellite passive microwave, IR morphed product (cMOR)] appear “most representative”; however, the climatology is short (2003–07) and the field is generally drier than the consensus. Of the conventional products, decadal variability of climate interpolated rain gauges (DEKL), World Climate Research Programme’s (WCRP) blended rain gauges, the Comprehensive Ocean–Atmosphere Data Set (COADS), and an operational climate anomaly monitoring system of NCEP (CAMS) perform well. Among the satellite estimators, the Global Precipitation Climatology Project’s blended gauge and IR satellite (GPCP) and outgoing longwave radiation (OLR) capture the key features and ocean–island transitions. The Center for Ocean–Land–Atmosphere Studies [COLA; the coupled model, part of the Coupled Model Intercomparison Project (CMIP, phase 3)] and the climate forecast system of the NCEP (CFS) models perform reasonably, but NCAR’s Parallel Climate Model (PCM; the CGCM’s historical run of CMIP3) fares poorly. The version 2 hindcast of the operational Medium-Range Forecast (MRF) weather prediction model (REAN) captures the smaller wet zones and topographically enhanced features, but it does not handle the broad oceanic dry zones well, as the input from the operational climate data assimilation system of NCEP (CDAS) has a wet bias. Of the various key rainfall features, high rainfall over southern Cuba and the rain shadow west of Hispanola are poorly handled by most products. The wet axis north of Trinidad and the dry zone north of Venezuela are well represented in many climatologies.
Impact of Satellite-Derived Rapid-Scan Wind Observations on Numerical Model Forecasts of Hurricane Katrina
Authors: Langland Rolf H. , Velden Christopher , Pauley Patricia M. , Berger Howard 
Published: November 2008

Abstract
The impacts of special Geostationary Operational Environmental Satellite (GOES) rapid-scan (RS) wind observations on numerical model 24–120-h track forecasts of Hurricane Katrina are examined in a series of data assimilation and forecast experiments. The RS wind vectors are derived from geostationary satellites by tracking cloud motions through successive 5-min images. In these experiments, RS wind observations are added over the area 15°–60°N, 60°–110°W, and they supplement the observations used in operational forecasts. The inclusion of RS wind observations reduces errors in numerical forecasts of the Katrina landfall position at 1200 UTC 29 August 2005 by an average of 12% compared to control cases that include “targeted” dropsonde observations in the Katrina environment. The largest average improvements are made to the 84- to 120-h Katrina track forecasts, rather than to the short-range track forecasts. These results suggest that RS wind observations can potentially be used in future cases to improve track forecasts of tropical cyclones.
Meta-analysis of genome-wide expression patterns associated with behavioral maturation in honey bees
Authors: Adams Heather A , Southey Bruce R , Robinson Gene E , Rodriguez-Zas Sandra L 
Published: November 2008

Abstract

Background
The information from multiple microarray experiments can be integrated in an objective manner via meta-analysis. However, multiple meta-analysis approaches are available and their relative strengths have not been directly compared using experimental data in the context of different gene expression scenarios and studies with different degrees of relationship. This study investigates the complementary advantages of meta-analysis approaches to integrate information across studies, and further mine the transcriptome for genes that are associated with complex processes such as behavioral maturation in honey bees. Behavioral maturation and division of labor in honey bees are related to changes in the expression of hundreds of genes in the brain. The information from various microarray studies comparing the expression of genes at different maturation stages in honey bee brains was integrated using complementary meta-analysis approaches.

Results
Comparison of lists of genes with significant differential expression across studies failed to identify genes with consistent patterns of expression that were below the selected significance threshold, or identified genes with significant yet inconsistent patterns. The meta-analytical framework supported the identification of genes with consistent overall expression patterns and eliminated genes that exhibited contradictory expression patterns across studies. Sample-level meta-analysis of normalized gene-expression can detect more differentially expressed genes than the study-level meta-analysis of estimates for genes that were well described by similar model parameter estimates across studies and had small variation across studies. Furthermore, study-level meta-analysis was well suited for genes that exhibit consistent patterns across studies, genes that had substantial variation across studies, and genes that did not conform to the assumptions of the sample-level meta-analysis. Meta-analyses confirmed previously reported genes and helped identify genes (e.g. Tomosyn, Chitinase 5, Adar, Innexin 2, Transferrin 1, Sick, Oatp26F) and Gene Ontology categories (e.g. purine nucleotide binding) not previously associated with maturation in honey bees.

Conclusion
This study demonstrated that a combination of meta-analytical approaches best addresses the highly dimensional nature of genome-wide microarray studies. As expected, the integration of gene expression information from microarray studies using meta-analysis enhanced the characterization of the transcriptome of complex biological processes.
Comparative analysis of selected methods for the assessment of antimicrobial and membrane-permeabilizing activity: a case study for lactoferricin derived peptides
Authors: Sánchez-Gómez Susana , Lamata Marta , Leiva José , Blondelle Sylvie E , Jerala Roman , Andrä Jörg , Brandenburg Klaus , Lohner Karl , Moriyón Ignacio , Martínez-de-Tejada Guillermo 
Published: November 2008

Abstract

Background
Growing concerns about bacterial resistance to antibiotics have prompted the development of alternative therapies like those based on cationic antimicrobial peptides (APs). These compounds not only are bactericidal by themselves but also enhance the activity of antibiotics. Studies focused on the systematic characterization of APs are hampered by the lack of standard guidelines for testing these compounds. We investigated whether the information provided by methods commonly used for the biological characterization of APs is comparable, as it is often assumed. For this purpose, we determined the bacteriostatic, bactericidal, and permeability-increasing activity of synthetic peptides (n = 57; 9–13 amino acid residues in length) analogous to the lipopolysaccharide-binding region of human lactoferricin by a number of the most frequently used methods and carried out a comparative analysis.

Results
While the minimum inhibitory concentration determined by an automated turbidimetry-based system (Bioscreen) or by conventional broth microdilution methods did not differ significantly, bactericidal activity measured under static conditions in a low-ionic strength solvent resulted in a vast overestimation of antimicrobial activity. Under these conditions the degree of antagonism between the peptides and the divalent cations differed greatly depending on the bacterial strain tested. In contrast, the bioactivity of peptides was not affected by the type of plasticware (polypropylene vs. polystyrene). Susceptibility testing of APs using cation adjusted Mueller-Hinton was the most stringent screening method, although it may overlook potentially interesting peptides. Permeability assays based on sensitization to hydrophobic antibiotics provided overall information analogous – though not quantitatively comparable- to that of tests based on the uptake of hydrophobic fluorescent probes.

Conclusion
We demonstrate that subtle changes in methods for testing cationic peptides bring about marked differences in activity. Our results show that careful selection of the test strains for susceptibility testing and for screenings of antibiotic-sensitizing activity is of critical importance. A number of peptides proved to have potent permeability-increasing activity at subinhibitory concentrations and efficiently sensitized Pseudomonas aeruginosa both to hydrophilic and hydrophobic antibiotics.
Systemic resistance and lipoxygenase-related defence response induced in tomato by Pseudomonas putidastrain BTP1
Authors: Akram Adam , Ongena Marc , Duby Francéline , Dommes Jacques , Thonart Philippe 
Published: November 2008

AbstractBackgroundPrevious studies showed the ability ofPseudomonas putidastrain BTP1 to promote induced systemic resistance (ISR) in different host plants. Since ISR is long-lasting and not conducive for development of resistance of the targeted pathogen, this phenomenon can take part of disease control strategies. However, in spite of the numerous examples of ISR induced by PGPR in plants, only a few biochemical studies have associated the protective effect with specific host metabolic changes.ResultsIn this study, we showed the protective effect of this bacterium in tomato againstBotrytis cinerea. Following treatment byP. putidaBTP1, analyses of acid-hydrolyzed leaf extracts showed an accumulation of antifungal material after pathogen infection. The fungitoxic compounds thus mainly accumulate as conjugates from which active aglycones may be liberated through the activity of hydrolytic enzymes. These results suggest that strain BTP1 can elicit systemic phytoalexin accumulation in tomato as one defence mechanism. On another hand, we have shown that key enzymes of the lipoxygenase pathway are stimulated in plants treated with the bacteria as compared with control plants. Interestingly, this stimulation is observed only after pathogen challenge in agreement with the priming concept almost invariably associated with the ISR phenomenon.ConclusionThrough the demonstration of phytoalexin accumulation and LOX pathway stimulation in tomato, this work provides new insights into the diversity of defence mechanisms that are inducible by non-pathogenic bacteria in the context of ISR.
A novel HSF4gene mutation (p.R405X) causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan
Authors: Sajjad Naheed , Goebel Ingrid , Kakar Naseebullah , Cheema Abdul Majeed , Kubisch Christian , Ahmad Jamil 
Published: November 2008

Abstract

Background
Hereditary cataracts are most frequently inherited as autosomal dominant traits, but can also be inherited in an autosomal recessive or X-linked fashion. To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene HSF4 (Genbank accession number NM_001040667). Here, we describe a family from Pakistan with the first nonsense mutation in HSF4 thus expanding the mutational spectrum of this heat shock transcription factor gene.

Methods
A large consanguineous Pakistani family with autosomal recessive cataracts was collected from Quetta. Genetic linkage analysis was performed for the common known autosomal recessive cataracts loci and linkage to a locus containing HSF4 (OMIM 602438) was found. All exons and adjacent splice sites of the heat shock transcription factor 4 gene (HSF4) were sequenced. A mutation-specific restriction enzyme digest (HphI) was performed for all family members and unrelated controls.

Results
The disease phenotype perfectly co-segregated with markers flanking the known cataract gene HSF4, whereas other autosomal recessive loci were excluded. A maximum two-point LOD score with a Zmax = 5.6 at θ = 0 was obtained for D16S421. Direct sequencing of HSF4 revealed the nucleotide exchange c.1213C > T in this family predicting an arginine to stop codon exchange (p.R405X).

Conclusion
We identified the first nonsense mutation (p.R405X) in exon 11 of HSF4 in a large consanguineous Pakistani family with autosomal recessive cataract.