bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel events associated with phenotypic reversion of a P element mutant in Drosophila melanogaster
Authors: Anderson Kyle J. , Davis Monica M. , Hodgetts Ross B.
Published: November 2006

Transposable P elements have been used extensively for Drosophila mutagenesis. While their mutagenic activity has long been recognized, the mechanisms by which P elements cause mutations are varied and not completely understood. We describe here an experiment to replace a P element at vestigial (vg) that caused a strong mutant phenotype (P[21-3]) with a P element (P[21]) known to produce a very weak phenotype when inserted at vg. In addition to testing the feasibility of P element replacements at vg, our investigation led to the production of 7 new vg alleles and 1 apparent second site suppressor. All the vg21-3 revertants that we recovered had a P element inserted into the first exon of vg at the same location and in the same orientation as the original element in vg21-3, providing a unique opportunity to study the mechanism of transposon mutagenesis. A majority of the revertants arose from a previously described event: internal deletion of P sequences, including the P promoter. In addition, 3 novel reversions of the vg21-3 wing phenotype were recovered. The wings of homozygous vg21r36 flies were normal. However, vg21r36 in combination with a deletion of the vg locus exhibited a strong mutant wing phenotype. This was surprising, because the P element insertion in vg21r36 was very similar to that found in the vg21 allele, which showed only slight nicking of the wings in combination with a deletion. In vg21r4, reversion was caused by a tandem insertion of P[21] and the original P[21-3] element present in vg21-3. Finally, the vg21r7 revertant had a P[21-3] insert at vg and 3 additional P elements elsewhere in the genome. We hypothesize that reversion in the 3 novel cases might be caused by P repressor produced by an element at vg or, in the case of vg21r7, elsewhere in the genome. This raises an interesting aspect of P element evolution. While P transposons produce mutations that might prove deleterious to their host, their success in invading the genome of D. melanogaster may be explained by their ability to silence those same mutations by a range of repressor-producing elements.
Resistance training reduces whole-body protein turnover and improves net protein retention in untrained young males
Authors: Hartman Joseph W. , Moore Daniel R. , Phillips Stuart M.
Published: November 2006

It is thought that resistance exercise results in an increased need for dietary protein; however, data also exists to support the opposite conclusion. The purpose of this study was to determine the impact of resistance exercise training on protein metabolism in novices with the hypothesis that resistance training would reduce protein turnover and improve whole-body protein retention. Healthy males (n = 8, 22 ± 1 y, BMI = 25.3 ± 1.8 kg·m–2) participated in a progressive whole-body split routine resistance-training program 5d/week for 12 weeks. Before (PRE) and after (POST) the training, oral [15N]-glycine ingestion was used to assess nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB), and net protein balance (NPB = PS – PB). Macronutrient intake was controlled over a 5d period PRE and POST, while estimates of protein turnover and urinary nitrogen balance (Nbal = Nin – urine Nout) were conducted. Bench press and leg press increased 40% and 50%, respectively (p < 0.01). Fat- and bone-free mass (i.e., lean muscle mass) increased from PRE to POST (2.5 ± 0.8 kg, p < 0.05). Significant PRE to POST decreases (p <0.05) occurred in Q (0.9 ± 0.1 vs. 0.6 ± 0.1 g N·kg–1·d–1), PS (4.6 ± 0.7 vs. 2.9 ± 0.3 g·kg–1·d–1), and PB (4.3 ± 0.7 vs. 2.4 ± 0.2 g·kg–1·d–1). Significant training-induced increases in both NPB (PRE = 0.22 ± 0.13 g·kg–1·d–1; POST = 0.54 ± 0.08 g·kg–1·d–1) and urinary nitrogen balance (PRE = 2.8 ± 1.7 g N·d–1; POST = 6.5 ± 0.9 g N·d–1) were observed. A program of resistance training that induced significant muscle hypertrophy resulted in reductions of both whole-body PS and PB, but an improved NPB, which favoured the accretion of skeletal muscle protein. Urinary nitrogen balance increased after training. The reduction in PS and PB and a higher NPB in combination with an increased nitrogen balance after training suggest that dietary requirements for protein in novice resistance-trained athletes are not higher, but lower, after resistance training.
Which common NIRS variable reflects muscle estimated lactate threshold most closely?
Authors: Wang Lixin , Yoshikawa Takahiro , Hara Taketaka , Nakao Hayato , Suzuki Takashi , Fujimoto Shigeo
Published: November 2006

Various near-infrared spectroscopy (NIRS) variables have been used to estimate muscle lactate threshold (LT), but no study has determined which common NIRS variable best reflects muscle estimated LT. Establishing the inflection point of 2 regression lines for deoxyhaemoglobin (ΔHHbi.p.), oxyhaemoglobin (ΔO2Hbi.p.), and tissue oxygenation index (TOIi.p.), as well as for blood lactate concentration, we then investigated the relationships between NIRS variables and ventilatory threshold (VT), LT, or maximal tissue hemoglobin index (nTHImax) during incremental cycling exercise. ΔHHbi.p. and TOIi.p. could be determined for all 15 subjects, but ΔO2Hbi.p. was determined for only 11 subjects. The mean absolute values for the 2 measurable slopes of the 2 continuous linear regression lines exhibited increased changes in 3 NIRS variables. The workload and VO2 at ΔO2Hbi.p. and nTHImax were greater than those at VT, LT, ΔHHbi.p., and TOIi.p.. For workload and VO2, ΔHHbi.p. was correlated with VT and LT, whereas ΔO2Hbi.p. was correlated with nTHImax, and TOIi.p. with VT and nTHImax. These findings indicate that ΔO2Hb strongly corresponds with local perfusion, and TOI corresponds with both local perfusion and deoxygenation, but that ΔHHb can exactly determine deoxygenation changes and reflect O2 metabolic dynamics. The finding of strongest correlations between ΔHHb and VT or LT indicates that ΔHHb is the best variable for muscle LT estimation.
Phosphorus removal in a waste-stabilization pond containing limestone rock filters
Authors: Strang T J , Wareham D G
Published: November 2006

This study analyzed samples taken along internal transects through a small waste-stabilization pond system in New Zealand that had rock filters installed between the final maturation cells. The aim of the study was to determine the respective importance of the ponds and rock filters for phosphorus (P) removal since routine monitoring from the preceding 2 months had indicated effluent P levels below 2 g/m3 for influent levels around 9 g/m3. Despite the filters being constructed from a reactive sorbent (i.e., limestone) it was found that phosphorus removal was mainly occurring in the ponds. A solubility analysis suggested that phosphorus removal may have been due to moderate calcium hardness levels of around 60 g/m3 as Ca2+, while an analysis of sludge samples in the system suggested that the ratio of calcium to phosphorus in the sludge was consistent with the precipitation of phosphorus as calcium hydroxyapatite.Key words: waste-stabilization ponds, phosphorus removal, limestone rock filters.
Variability of North American regulatory guidance for heavy metal contamination of residential soil
Authors: Jennings Aaron A , Petersen Elijah J
Published: November 2006

The health implications and remediation obligations of contaminated urban soils are significant issues in many North American cities. Remediation guidance for soils is evolving and shifting from values based on geochemical background approximations to values based on health risks. This analysis examines residential-soil guidance variability among the states and provinces of North America for Cd, Cr, Cu, Ni, Pb, and Zn. For some metals, values vary by as much as 5 orders of magnitude. Nonparametric comparisons are used to illustrate the degree to which current standards differ and to examine the spatial distribution of differences. Parametric statistical analysis is used to examine the significance of variations, and to determine if correlations exist in the structure of guidance values. Hazard index analysis is also used to examine how guidance value differences impact site risk assessments. Results indicate that most of the current variation can be explained as plausible randomness if determining maximum acceptable soil exposures is a random process. Differences between the statistical properties of Cd, Cr, Cu, Ni, and Zn guidance and that of Pb also demonstrate the influence that national leadership can have on stabilizing guidance. Key words: heavy metals, remediation guidance values, residential soil contamination, risk analysis, hazard index analysis.
Exploring the role of hydrogen peroxide in the microwave advanced oxidation process: solubilization of ammonia and phosphates
Authors: Wong W T , Chan W I , Liao P H , Lo K V , Mavinic D S
Published: November 2006

The focus of this study was to investigate the combined effects of hydrogen peroxide concentration and acid hydrolysis on ammonia and ortho-phosphate solubilization for subsequent struvite formation. A lower microwave temperature regime between 60 and 120 °C was of interest in this study because of the greater amount of polyphosphates found in the treated secondary sludge at these temperatures. At microwave-heating temperatures of 100 °C and 120 °C, it was found that increasing the hydrogen peroxide concentration resulted in an increased phosphorus and ammonia solubilization. At a reaction time of only 5 min, the combination of hydrogen peroxide and acid hydrolysis resulted in up to 61% of total phosphorus and 36% of TKN released into solution, as soluble ortho-phosphate and ammonia, respectively. The amount of soluble nitrogen in solution after microwave treatment was found to increase with the hydrogen peroxide concentration. Up to 39% of the total soluble nitrogen could be released into solution. Furthermore, the addition of hydrogen peroxide resulted in a dramatic decrease in the PO4:NH3 molar ratio, an important factor controlling struvite formation. In terms of facilitating poly-P breakdown into ortho-phosphate in the acid hydrolysis process, hydrogen peroxide was found to be the most effective at 80 °C and at a concentration of 1.5 wt% H2O2. At temperatures of 100 and 120 °C, the amount of soluble ortho-phosphate increased with the hydrogen peroxide concentration. Key words: advanced oxidation process, ammonia nitrogen, hydrogen peroxide, microwave, phosphorus release, sludge, struvite.
Ionization potentials of nitriles — Photoelectron spectra of succinonitrile and glutaronitrile
Authors: Muchall Heidi M , Werstiuk Nick H
Published: November 2006

The He(I) photoelectron spectra of succinonitrile (1) and glutaronitrile (2), both with extensive overlap of ionization bands in the low-energy region, are reported. To assign ionizations, we studied the conformational behaviour and resulting ionization energy dependence of 1 and 2 computationally with the B3LYP/6-31+G(d) model chemistry based on the fact that it reliably reproduces the ionization potentials of eleven mono- and di-nitriles, both saturated and unsaturated. The correlation of proton affinities with observed ionization potentials of 1, 2, and malononitrile establishes the orbital sequence of four C≡N π orbitals followed by two nitrogen lone pair orbitals as the highest occupied molecular orbitals for all three compounds.Key words: photoelectron spectrum, ionization potential, conformational dependence, nitrile, DFT.
Activities and survival of endophytic bacteria in white clover (Trifolium repensL.)
Authors: Burch Gabriela , Sarathchandra Upali
Published: November 2006

In this study, the genera, abundance, and activities of endophytic bacteria in field-grown white clover (Trifolium repens) and the fate of introduced antibiotic-tolerant bacteria in white clover tissues were investigated. Pseudomonas, Pantoea, and Corynebacterium were the most frequently isolated endophytic bacteria genera, whereas Xanthomonas, Microbacterium, and Cellulomonas occurred less frequently. The average bacterial populations in stolons and roots were approximately 100 000 colony-forming units (CFU) (g wet mass)–1. Of the 28 strains tested for activity, none were chitinolytic or able to inhibit the root pathogen Codinaea fertilis in vitro. However, Fusarium oxysporum and Cylindrocladium scoparium were inhibited by one and five strains, respectively. Four of seven strains tested depressed clover seedling growth. In pot experiments, colonization and recovery of spontaneous rifampicin-tolerant mutants (Rif+) of bacteria were studied in clover plants for periods up to 20 weeks. The strains used, sourced from white clover (endophytic and rhizoplane) and organic compost, had previously shown growth promotion potential of white clover seedlings by increasing plant mass and decreasing nematode numbers. In one experiment in this present study, five Rif+strains were individually inoculated onto white clover seedlings, all five were re-isolated from shoots after 6 weeks and four strains were re-isolated after 20 weeks (numbers of Rif+bacteria ranged from 51 to 200 CFU (g wet mass)–1). No Rif+bacteria were isolated from root tissue at either time. In the second experiment, conducted with two strains of Rif+bacteria, the population was highest in the shoots (range >500 CFU of Rif+bacteria (g shoot fresh mass)–1) in weeks 2 and 3, declining to <200 CFU in week 5. Again, no Rif+bacteria could be detected in roots. No Rif+bacteria were recovered after 14 weeks for one of the strains. It appears that the main route of bacterial entry into seedlings was through stomata and that bacteria remained in the aerial parts of plants rather than migrating to the roots.Key words: endophytic bacteria, clover, microbial biological control, nematode.
Chitinase production during interaction of Trichoderma aggressivum and Agaricus bisporus
Authors: Guthrie Jennifer L , Castle Alan J
Published: November 2006

The competitor fungus Trichoderma aggressivum causes green mould disease, a potentially devastating problem of the commercial mushroom Agaricus bisporus. Due to the recent appearance of this problem, very little is known about the mechanisms by which T. aggressivum interacts with and inhibits A. bisporus. A mechanism generally used by Trichoderma species in the antagonism of other fungi is the secretion of cell wall degrading enzymes. In this study, we determined the activities of chitinases produced in dual cultures of these fungi over a 2 week period. Both intracellular and extracellular enzymes were studied. Agaricus bisporus produced N-acetylglucosaminidases with apparent molecular masses of 111, 105, and 96 kDa. Two resistant brown strains produced greater activities of the 96 kDa N-acetylglucosaminidase than susceptible off-white and white strains. This result suggested that this enzyme might have a role in the resistance of commercial brown strains to green mould disease. Trichoderma aggressivum produced three N-acetylglucosaminidases with apparent molecular masses of 131, 125, and 122 kDa, a 40 kDa chitobiosidase, and a 36 kDa endochitinase. The 122 kDa N-acetylglucosaminidase showed the greatest activity and may be an important predictor of antifungal activity.Key words: mushrooms, chitinases, Trichoderma, Agaricus.
Habitat selection in two sympatric Chinese skinks, Eumeces elegans and Sphenomorphus indicus: do thermal preferences matter?
Authors: Du W.G. , Shou L. , Shen J.Y.
Published: November 2006

We studied the habitat selection and thermal biology of two sympatric Chinese skinks ( Eumeces elegans Boulenger, 1887 and Sphenomorphus indicus (Schmidt, 1928)) to test the effect of thermal preference on habitat partitioning. We measured thermal and structural attributes of the microhabitats occupied by these two skink species, as well as their field body temperatures and activity patterns. We then quantified the preferred body temperatures of these species in a thermal gradient. Compared with S. indicus, E. elegans occupied microhabitats with fewer trees, more rocks, and higher ambient temperatures. Active S. indicus were mainly found in the morning, whereas active E. elegans were found at noon. The thermal environment of the microhabitats at these two periods correlated with the skinks’ thermal preferences. Preferred temperatures of E. elegans were significantly higher than those of S. indicus. These results support (i) the hypothesis that habitat partitioning between ectotherms is related to interspecific differences in thermal requirements; (ii) the labile hypothesis that describes the adaptability of thermal physiology, because the two sympatric skinks, which select different thermal environments, differed in thermal physiology; and (iii) the cold-climate hypothesis that explains the evolution of viviparity, because viviparous S. indicus occupy colder habitats than do oviparous E. elegans.
Predator, but not conspecific, chemical cues influence pond selection by recently metamorphosed Iberian green frogs,Rana perezi
Authors: Gonzalo Adega , Cabido Carlos , Galán Pedro , López Pilar , Martín José
Published: November 2006

In amphibians, adults and larvae have different ecological requirements that could force recently metamorphosed individuals to disperse. The presence of chemical cues of conspecifics and predators could provide information about habitat quality, which might influence the juveniles’ settlement decisions. We examined in the laboratory whether pond choice by recently metamorphosed Iberian green frogs ( Rana perezi Seoane, 1885) is influenced by the presence of chemical cues from conspecifics and (or) from predators in the water. Our results suggest that frogs were able to detect the presence of chemical cues of snake predators in the water and that they avoided entering such ponds. However, frogs did not show either attraction or avoidance of ponds with conspecific chemical cues. Thus, juvenile frogs may select their postmetamorphic territories based on the lack of predation risk, and possibly on some habitat features, but not on the presence of conspecifics.
The ultrastructure of sea turtle eggshell does not contribute to interspecies variation in fungal invasion of the egg
Authors: Phillott A.D. , Parmenter C.J.
Published: November 2006

The eggshells of green ( Chelonia mydas (L., 1758)), loggerhead (Caretta caretta (L., 1758)), hawksbill ( Eretmochelys imbricata (L., 1766)), and flatback ( Natator depressus (Garman, 1880)) sea turtles nesting in eastern Australia were examined by scanning electron microscopy to determine if the ultrastructure was contributing to interspecific variation in fungal invasion of eggs. The eggshells of all species investigated were of similar structure (outer inorganic layer of aragonite crystals and an inner organic fibrillar layer) and of similar thickness. Well-defined pores that would allow direct entry of fungal hyphae or spores were not present in any species. It was concluded that the eggshell ultrastructure does not allow direct access by fungal hyphae or spores and does not contribute to interspecific variation in the vulnerability of loggerhead sea turtle eggs to fungal infection.
Immigrant Integration in Europe: Empirical Research
Authors: Givens Terri E.
Published: November 2006

▪ Abstract  Most European countries are examining how they have sought to integrate immigrants in the past and how they might change their policies to avoid some of the problems exhibited in immigrant and minority communities today. Discrimination and issues of racism, including the rise of anti-immigrant radical right parties, have become important, as evidenced in part by the passage of the European Union's Racial Equality Directive in 2000. This essay reviews comparative research in political science on immigrant integration in Western Europe. It discusses multiculturalism and assimilation, party politics, antidiscrimination policy, and policy at the European Union level.
Differential regulation of myofilament protein isoforms underlying the contractility changes in skeletal muscle unloading
Authors: Yu Zhi Bin , Gao Fang , Feng Han Zhong , Jin Jian-Ping
Published: November 2006

Weight-bearing skeletal muscles change phenotype in response to unloading. Using the hindlimb suspension rat model, we investigated the regulation of myofilament protein isoforms in correlation to contractility. Four weeks of continuous hindlimb unloading produced progressive atrophy and contractility changes in soleus but not extensor digitorum longus muscle. The unloaded soleus muscle also had decreased fatigue resistance. Along with the decrease of myosin heavy chain isoform I and IIa and increase of IIb and IIx, coordinated regulation of thin filament regulatory protein isoforms were observed: γ- and β-tropomyosin decreased and α-tropomyosin increased, resulting in an α/β ratio similar to that in normal fast twitch skeletal muscle; troponin I and troponin T (TnT) both showed decrease in the slow isoform and increases in the fast isoform. The TnT isoform switching began after 7 days of unloading and TnI isoform showed detectable changes at 14 days while other protein isoform changes were not significant until 28 days of treatment. Correlating to the early changes in contractility, especially the resistance to fatigue, the early response of TnT isoform regulation may play a unique role in the adaptation of skeletal muscle to unloading. When the fast TnT gene expression was upregulated in the unloaded soleus muscle, alternative RNA splicing switched to produce more high molecular weight acidic isoforms, reflecting a potential compensation for the decrease of slow TnT that is critical to skeletal muscle function. The results demonstrate that differential regulation of TnT isoforms is a sensitive mechanism in muscle adaptation to functional demands.
Evaluation of emphysema severity and progression in a rabbit model: comparison of hyperpolarized 3He and 129Xe diffusion MRI with lung morphometry
Authors: Mata Jaime F. , Altes Talissa A. , Cai Jing , Ruppert Kai , Mitzner Wayne , Hagspiel Klaus D. , Patel Bina , Salerno Michael , Brookeman James R. , de Lange Eduard E. , Tobias William A. , Wang Hsuan-Tsung J. , Cates Gordon D. , Mugler John P.
Published: November 2006

The apparent diffusion coefficients (ADCs) of hyperpolarized 3He and 129Xe gases were measured in the lungs of rabbits with elastase-induced emphysema and correlated against the mean chord length from lung histology. In vivo measurements were performed at baseline and 2, 4, 6, and 8 wk after instillation of elastase (mild and moderate emphysema groups) or saline (control group). ADCs were determined from acquisitions that used two b values. To investigate the effect of b value on the results, b-value pairs of 0 and 1.6 s/cm2 and 0 and 4.0 s/cm2 were used for 3He, and b-value pairs of 0 and 5.0 s/cm2 and 0 and 10.0 s/cm2 were used for 129Xe. At 8 wk after instillation, the rabbits were euthanized, and the lungs were analyzed histologically and morphometrically. ADCs for the rabbits in the control group did not change significantly from baseline to week 8, whereas ADCs for the rabbits in the emphysema groups increased significantly ( P < 0.05) for all gas and b-value combinations except 129Xe with the b-value pair of 0 and 5.0 s/cm2. The largest percent change in mean ADC from baseline to week 8 (15.3%) occurred with 3He and the b-value pair of 0 and 1.6 s/cm2 for rabbits in the moderate emphysema group. ADCs (all b values) were strongly correlated ( r = 0.62–0.80, P < 0.001) with mean chord lengths from histology. These results further support the ability of diffusion-weighted MRI with hyperpolarized gases to detect regional and global structural changes of emphysema within the lung.
Biweights and *‐homomorphisms of partial *‐algebras
Authors: Antoine Jean-Pierre , Trapani Camillo , Tschinke Francesco
Published: November 2006

Consider two partial *‐algebras, 1 and 2, and an *‐homomorphism Φ from 1 into 2. Given a biweight ϕ on 2, we discuss conditions under which the natural composition ϕ∘Φ of ϕ and Φ is a biweight on 1. In particular, we examine whether the restriction of a biweight to a partial *‐subalgebra is again a biweight.
Weyl transforms associated with the Riemann‐Liouville operator
Authors: Hamadi N. B. , Rachdi L. T.
Published: November 2006

For the Riemann‐Liouville transform ℛα,  α ∈ ℝ+, associated with singular partial differential operators, we define and study the Weyl transforms Wσ connected with ℛα, where σ is a symbol in Sm,
m ∈ ℝ. We give criteria in terms of σ for boundedness and compactness of the transform Wσ.
Interleukin‐10 in the Pathophysiology of Inflammatory Bowel Disease: Increased Serum Concentrations During the Recovery Phase
Authors: Mitsuyama Keiichi , Tomiyasu Nobuo , Takaki Kosuke , Masuda Junya , Yamasaki Hiroshi , Kuwaki Kotaro , Takeda Teiko , Kitazaki Shigehiko , Tsuruta Osamu , Sata Michio
Published: November 2006

Using a specific enzyme‐linked immunosorbent assay, IL‐10 concentrations were measured in serum from 62 patients with
ulcerative colitis (UC), 43 with Crohn′s disease (CD), 25 with other colitides, and 44 normal
control subjects. Serum IL‐10 concentrations were increased in patients with
active UC but not in those with active CD when compared with normal control subjects. A time course study
showed that in patients with UC and CD, serum concentrations of IL‐6 and C‐reactive protein
increased during the acute phase and returned to normal as patients go into remission. Notably,
serum IL‐10 concentrations increased during the phase of disease resolution and declined
thereafter regardless of the treatment modality. Gel filtration analysis indicated that IL‐10
circulated predominantly as a dimer. In conclusion, this study shows that serum IL‐10 is
increased during disease recovery in patients with inflammatory bowel disease, and may be a
helpful marker in monitoring disease status.
Serum Endothelin‐1 and Transforming Growth Factor‐β Levels in the Newborns With Respiratory Distress
Authors: Benzer Derya , Aygun A. Denizmen , Godekmerdan Ahmet , (Citak) Kurt A. Nese , Akarsu Saadet , Yilmaz Erdal
Published: November 2006

The purpose of this present study was to evaluate the serum levels of ET‐1 and TGF‐β in the newborns with respiratory distress. In this study, newborns with respiratory distress hospitalized into the Newborn Intensive Care Unit were included. The highest values of ET‐1 and TGF‐β were obtained from newborns with diagnosis as meconium aspiration syndrome (5.70 ± 5.87
pg/mL and 3.75 ± 1.94 pg/mL, resp) in the sample obtained in the first six hours after birth, and these are statistically different from control group (P < .05). Also, same results were obtained for newborns with respiratory distress syndrome (3.37 ± 1.59 pg/mL and 2.05 ± 0.98 pg/mL, resp). After oxygen treatment, ET‐1 values obtained in the first six hours of life were decreased regularly in the following days (P < .05). In the differentiating diagnosis of the respiratory distress of newborns, the investigation of ET‐1 and TGF‐β levels is meaningful. The ET‐1 levels investigated in the first six hours is more useful in determining the prognosis, and repeating ET‐1 levels in the following days is more meaningful to determine clinical response.
A Sequential Blockade Strategy for the Design of Combination Therapies to Overcome Oncogene Addiction in Chronic Myelogenous Leukemia
Authors: Chen Rong , Gandhi Varsha , Plunkett William
Published: November 2006

Some tumors are dependent on the continued activity of a single oncogene for maintenance of their malignant phenotype. The best-studied example is the Bcr-Abl fusion protein in chronic myelogenous leukemia (CML). Although the clinical success of the Abl kinase inhibitor imatinib against chronic-phase CML emphasizes the importance of developing therapeutic strategies aimed at this target, resistance to imatinib poses a major problem for the ultimate success of CML therapy by this agent. We hypothesized a sequential blockade strategy that is designed to decrease the expression of the Bcr-Abl protein, with the goal of complementing the action of imatinib on kinase activity. In this study, flavopiridol, an inhibitor of transcription, homoharringtonine (HHT), a protein synthesis inhibitor, and imatinib were used singly and in combination against the Bcr-Abl-positive human CML cell line K562. Flavopiridol alone inhibited phosphorylation of the RNA polymerase II COOH-terminal domain, specifically reduced RNA polymerase II–directed mRNA synthesis, and decreased the Bcr-Abl transcript levels. HHT inhibited protein synthesis and reduced the Bcr-Abl protein level. Imatinib directly inhibited the kinase activity of Bcr-Abl. The combinations of flavopiridol and HHT and flavopiridol and imatinib synergistically decreased clonogenicity as evaluated by the median-effect method. Greater synergy was observed when HHT and imatinib were given sequentially compared with simultaneous administration. Imatinib-resistant Ba/F3 cells that were transfected to express the E255K and T315I mutations of Bcr-Abl were not cross-resistant to flavopiridol and HHT. These results provided a rationale for the combination of inhibitors of transcription and/or translation with specific kinase inhibitors. (Cancer Res 2006; 66(22): 10959-66)
Epigenetic Regulation of Tumor Endothelial Cell Anergy: Silencing of Intercellular Adhesion Molecule-1 by Histone Modifications
Authors: Hellebrekers Debby M.E.I. , Castermans Karolien , Viré Emmanuelle , Dings Ruud P.M. , Hoebers Nicole T.H. , Mayo Kevin H. , oude Egbrink Mirjam G.A. , Molema Grietje , Fuks François , van Engeland Manon , Griffioen Arjan W.
Published: November 2006

Tumors can escape from immunity by repressing leukocyte adhesion molecule expression on tumor endothelial cells and by rendering endothelial cells unresponsive to inflammatory activation. This endothelial cell anergy is induced by angiogenic growth factors and results in reduced leukocyte-vessel wall interactions, thereby attenuating infiltration of leukocytes into the tumor. This report describes a novel mechanism of endothelial cell anergy regulation. We recently reported that DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors have angiostatic activity. Here, we studied whether epigenetic mechanisms regulate this angiogenesis-mediated escape from immunity. We found that DNMT inhibitors 5-aza-2′-deoxycytidine and zebularine, as well as HDAC inhibitor trichostatin A, reexpressed intercellular adhesion molecule-1 (ICAM-1) on tumor-conditioned endothelial cells in vitro, resulting in restored leukocyte-endothelial cell adhesion. In addition, treatment with DNMT or HDAC inhibitors in vivo also restored ICAM-1 expression on tumor endothelial cells from two different mouse tumor models. Furthermore, leukocyte-vessel wall interactions in mouse tumors were increased by these compounds, as measured by intravital microscopy, resulting in enhanced leukocyte infiltration. We show that ICAM-1 down-regulation in tumor endothelial cells is associated with ICAM-1 promoter histone H3 deacetylation and loss of histone H3 Lys4 methylation but not with DNA hypermethylation. In conclusion, our data show that ICAM-1 is epigenetically silenced in tumor endothelial cells by promoter histone modifications, which can be overcome by DNMT and HDAC inhibitors, suggesting a new molecular mechanism based on which novel therapeutic approaches for cancer can be pursued. (Cancer Res 2006; 66(22): 10770-7)
Oncostatin M (OSM) Cytostasis of Breast Tumor Cells: Characterization of an OSM Receptor β–Specific Kernel
Authors: Underhill-Day Nicholas , Heath John K.
Published: November 2006

The interleukin-6 cytokine oncostatin M (OSM) induces potent growth-inhibitory and morphogenic responses in several different tumor cell types, highlighting the importance of OSM signaling mechanisms as targets for therapeutic intervention. The specific molecular pathways involved are not well understood, as OSM can signal through two separate heterodimeric receptor complexes, glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR) α and gp130/OSM receptor β (OSMRβ). In this investigation, we used a LIFR antagonist to help resolve signaling responses and identify patterns of gene expression elicited by the different receptor complexes. OSM-induced biological effects on breast tumor–derived cell lines were specifically mediated through the gp130/OSMRβ complex. Each cytokine tested exhibited differential signaling capability and manifested both shared and unique patterns of gene activation, emphasizing compositional differences in activator protein-1 transcription factor activity and expression. In particular, OSM strongly activated the c-Jun NH2-terminal kinase (JNK) serine/threonine kinase and downstream components, including activating transcription factor (ATF)/cyclic AMP-responsive element binding protein family member, ATF3. JNK/stress-activated protein kinase kinase inhibition abrogated cell morphogenesis induced by OSM, indicating an important role for this pathway in OSM specificity. These findings identify a core signaling/transcriptional mechanism specific to the OSMRβ in breast tumor cells. (Cancer Res 2006; 66(22): 10891-901)
Ciz1, a Novel DNA-Binding Coactivator of the Estrogen Receptor α, Confers Hypersensitivity to Estrogen Action
Authors: den Hollander Petra , Rayala Suresh K. , Coverley Dawn , Kumar Rakesh
Published: November 2006

The transcriptional activity of the estrogen receptor (ER) is affected by regulatory cofactors, including chromatin-remodeling complexes, coactivators, and corepressors. Coregulators are recruited to target gene promoters through protein-protein interactions with ER and function as linker molecules between the DNA, DNA-binding proteins, and DNA-modifying enzymes. We recently showed that Cip-interacting zinc finger protein 1 (Ciz1) participates in the regulation of the cell cycle in estrogen-stimulated breast cancer cells. Despite the emerging significance of Ciz1 in the biology of breast cancer cells, regulation of endogenous Ciz1 in hormone-responsive cancer cells remains unknown. To shed light on the role of Ciz1 in breast tumorigenesis, we defined the regulation of Ciz1 by the ER pathway and found that Ciz1 is an estrogen-responsive gene. We also discovered that Ciz1 protein, a DNA-binding factor, coregulates ER by enhancing ER transactivation activity by promoting the recruitment of the ER complex to the target gene chromatin. In addition, we found that Ciz1 overexpression confers estrogen hypersensitivity to breast cancer cells and promotes the growth rate, anchorage independency, and tumorigenic properties of breast cancer cells. These findings revealed the inherent role of Ciz1, a novel DNA binding and ER coactivator, in amplifying estrogenic responses and promoting breast cancer tumorigenesis. (Cancer Res 2006; 66(22): 11021-9)
Steroid Receptor Coactivator-3 and Activator Protein-1 Coordinately Regulate the Transcription of Components of the Insulin-Like Growth Factor/AKT Signaling Pathway
Authors: Yan Jun , Yu Cheng-Tai , Ozen Mustafa , Ittmann Michael , Tsai Sophia Y. , Tsai Ming-Jer
Published: November 2006

Steroid receptor coactivator (SRC)-3, also called amplified in breast cancer 1, is a member of the p160 nuclear receptor coactivator family involved in transcriptional regulation of target genes. SRC-3 is frequently amplified and/or overexpressed in hormone-sensitive and hormone-insensitive tumors. We reported previously that SRC-3 stimulated prostate cell growth in a hormone-independent manner through activation of AKT signaling pathway. However, the underlying mechanism remains undefined. Here, we exploited the mifepristone-induced SRC-3 LNCaP prostate cancer cell line generated in our laboratory to identify SRC-3-regulated genes by oligonucleotide microarray analysis. We found that SRC-3 up-regulates the expression of multiple genes in the insulin-like growth factor (IGF)/AKT signaling pathway that are involved in cell proliferation and survival. In contrast, knockdown of SRC-3 in PC3 (androgen receptor negative) prostate cancer cells and MCF-7 breast cancer cells reduces their expression. Similarly, in prostate glands of SRC-3 null mice, expressions of these components in the IGF/AKT signal pathway are also reduced. Chromatin immunoprecipitation assay revealed that SRC-3 was directly recruited to the promoters of these genes, indicating that they are direct targets of SRC-3. Interestingly, we showed that recruitment of SRC-3 to two target promoters, IRS-2 and IGF-I, requires transcription factor activator protein-1 (AP-1). Taken together, our results clearly show that SRC-3 and AP-1 can coordinately regulate the transcription of multiple components in the IGF/AKT pathway to ensure ligand-independent cell proliferation and survival of cancer cells. (Cancer Res 2006; 66(22): 11039-46)
A Causal Role for the Human Tumor Antigen Preferentially Expressed Antigen of Melanoma in Cancer
Authors: Epping Mirjam T. , Bernards René
Published: November 2006

Tumor antigens are of interest as diagnostic and prognostic markers and potential therapeutic targets. The tumor antigen preferentially expressed antigen of melanoma (PRAME) is frequently overexpressed in a wide variety of cancers and is a prognostic marker for clinical outcome. It has been shown recently that PRAME functions as a repressor of retinoic acid signaling. Here, we discuss this novel insight in the context of the increasing interest in tumor antigens as targets for therapy. (Cancer Res 2006; 66(22): 10639-42)
Laryngeal Microweb and Vocal Nodules
Authors: Ruiz Daniela Maria Cury Ferreira , Pontes Paulo , Behlau Mara , Richieri-Costa A.
Published: November 2006

The etiology and pathogenesis of laryngeal microwebs are heterogeneous, and in most cases they are an incidental finding. It has also been suggested that microwebs could be a familial trait, representing a postblastogenic embryonic vestigial structure that might alter the biomechanical and vibratory properties of the vocal fold. Vocal nodules are small benign swellings along the margins of the vocal cords, with preferential location at the junction of the anterior and middle thirds, and usually resulting from mechanical trauma. The authors studied a sample of 107 patients with vocal nodules, looking for a possible correlation with microwebs due to the predicted involvement in the vibration of vocal cord margins. Glottic proportion, type of glottic closure, nodule location and the main complaints in patients with microwebs were compared with those in a sample of patients without microwebs. In the present study, microwebs were found in 9.4% of the patients, who showed much smaller glottic proportion than patients with micronodules only. Furthermore, vocal nodule location was not related to the presence and/or absence of laryngeal microwebs.
Two Patients with Tremor Caused by Cortical Lesions
Authors: Balci Kemal , Utku Ufuk , Cobanoglu Sebahattin
Published: November 2006

Myoclonic tremor due to cortical lesions is a rare condition and must be distinguished from other causes of tremor. This is because the treatment strategies of tremor may differ due to the various etiologies. We present here two cases with myoclonic tremor caused by parietal cortical lesions showing tremulous finger movement provoked by action and posture. Clinical and electrophysiological features of the patients were reported and compared with the features of the patients with cortical tremor in association with cortical reflex myoclonus. Both of our patients responded well to anticonvulsants such as valproate and clonazepam. In patients with acute postural tremor, cortical lesions such as mass occupying lesions, ischemic lesions and arteriovenous malformations should be taken into consideration.
Mannheim Carotid Intima-Media Thickness Consensus (2004–2006)
Authors: Touboul P.-J. , Hennerici M.G. , Meairs S. , Adams H. , Amarenco P. , Bornstein N. , Csiba L. , Desvarieux M. , Ebrahim S. , Fatar M. , Hernandez Hernandez R. , Jaff M. , Kownator S. , Prati P. , Rundek T. , Sitzer M. , Schminke U. , Tardif J.-C. , Taylor A. , Vicaut E. , Woo K.S. , Zannad F. , Zureik M.
Published: November 2006

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to ‘treat IMT values’ nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.
A Fugue About Grief
Authors: Lee Karen V.
Published: November 2006

The following autoethnography reveals the author's personal struggle when informed about a suicide. The resulting emotional turmoil causes her to shift forward, backward, and sideways through memories of death during a summer beach outing with her daughter. The narrative demonstrates how she copes with her inner anguish while striving to preserve a happy union. She reveals the painful irony of living simultaneously in a culture of happiness and culture of grief. In doing so, her narrative implicates the stories that encourage parents to suppress emotions from their children. In the end, autoethnography becomes an epiphany that heals her from the tragedy as she gains a deeper understanding about the personal and cultural influences shaping her desire for pedagogical thoughtfulness.
Quantitative mineralogical analysis of some Bangladesh soils with X-ray, ion exchange and selective dissolution techniques
Authors: Islam A. K. M. E. , Lotse E. G.
Published: November 2006

Fine clay, coarse clay, and silt fractions of four Bangladesh soils were studied using XRD, ion exchange, and selective dissolution techniques. Constants for the XRD intensity-weight proportion relationships were derived using these techniques. Smectite and mica were found to be dominant in Batra and Ghior soils, whereas kaolinite and mica were dominant in the Naraibag and Ghatail soils. Other minerals present were vermiculite, vermiculite with hydroxyaluminium interlayers, chlorite, randomly interstratified chlorite-mica, feldspar, quartz, and trace amounts of amphibole. The amorphous material content varied between 1 and 11% and decreased with increasing particle size. No crystalline iron oxides were detected in untreated clay fractions.
Electron diffraction and the study of ferrihydrite coatings on kaolinite
Authors: Jones Angela A. , Saleh A. M.
Published: November 2006

Selected-area electron diffraction has been used to examine ferrihydrite coatings on kaolinite crystals and is shown to provide a sensitive means of detection. It also gives better diffraction patterns of ferrihydrite than does XRD and the patterns sometimes give additional indications of the crystal size. It is suggested that the technique may be useful in examining other coatings on soils and clays.
Infrared absorption of surface hydroxyl groups and lattice vibrations in lepidocrocite (γ-FeOOH) and boehmite (γ-AIOOH)
Authors: Lewis D. G. , Farmer V. C.
Published: November 2006

Boehmite and lepidocrocite, in the form of thin plates with well-developed (010) faces parallel to the constituent layers, show one predominant absorption band due to OH stretching of two-coordinated surface hydroxyl groups, which are shown to be unreactive towards phosphate. In very fine grained preparations of lepidocrocite, two other species of surface hydroxyl are detected, presumably associated with (100) and (001) faces. Marked differences in the frequencies of bulk vibrations between platy and rod-shaped lepidocrocite preparations can be explained partly by their crystal morphology, and partly by degree of crystalline order.
Methode diffractometrique de caracterisation des états d'hydratation des smectites stabilité relative des couches d'eau inserées
Authors: Brahim J. Ben , Armağan N. , Besson G. , Tchoubar C.
Published: November 2006

Resume

Nous décrivons un montage expérimental permettant d'obtenir, avec une bonne précision, des diagrammes de diffraction X de poudre d'argile dans un état hydraté homogène et de suivre la cinétique du processus d'hydratation. Nous avons pu déterminer, dans le cas de l'état homogène à une couche d'eau d'une beidellite sodique, la position des cations échangeables, le nombre total de molécules d'eau par maille et leurs coordonnéesz, en utilisant une méthode de modèle basée sur la comparaison des profils expérimentaux et calculés des réflexions 00l. De plus nous avons comparé les caractéristiques structurales et en particulier le mode d'empilement des feuillets de l'état monocouche avec celui des états anhydre et bicouche. L'analyse du profil des réflexions 00lmontre l'existence de fluctuations autour d'un espacement basal moyen. Ces fluctuations sont interprétées comme provenant de l'hétérogénéité de la distribution des charges dans le feuillet. Enfin, un processus théorique d'hydratation et de déshydratation est proposé.
Clay mineral variation in Tertiary sediments from the eastern flank of the Niger Delta
Authors: Braide S. P. , Huff W. D.
Published: November 2006

Detailed clay mineralogical and chemical analyses of well cuttings of Tertiary sediments from two wells, Uruan-1 and Uda-1, on the eastern flank of the Niger delta, have been made in an attempt to investigate clay mineral burial diagenesis. The clay mineralogy indicates a transformation of smectite to an interstratified illite-smectite (I/S) phase. The relationship between ordered and random interlayering, however, is nonsystematic. The chemistry of the <0·1µm size fraction shows some tendency towards a net gain in K2O and Al2O3and a net loss in SiO2with depth, but the relationship does not correlate well with the thermal gradient. The distribution of kaolinite and chlorite in both wells appears to be unrelated in any regular way to smectite transformation and these two minerals are considered to be either the products of other diagenetic reactions affecting various stratigraphic levels, or the result of primary sediment deposition. In well Uda-1, kaolinite decreases in relative abundance with depth. This trend has been interpreted elsewhere as indicative of a transition from nonmarine to marine facies. The results of this study indicate that lack of ion mobility, rather than availability, is a significant factor in retarding the formation of ordered I/S with depth, and that lithology, overpressuring, carbonate cement, and original smectite layer charge may be controlling factors in the smectite → illite transformation.