bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of c-Met and prevention of spontaneous metastatic spreading by the 2-indolinone RPI-1
Authors: Cassinelli Giuliana , Lanzi Cinzia , Petrangolini Giovanna , Tortoreto Monica , Pratesi Graziella , Cuccuru Giuditta , Laccabue Diletta , Supino Rosanna , Belluco Sara , Favini Enrica , Poletti Anna , Zunino Franco 
Published: September 2006

Abstract
Hepatocyte growth factor (HGF) and its tyrosine kinase receptor Met play a pivotal role in the tumor metastatic phenotype and represent attractive therapeutic targets. We investigated the biochemical and biological effects of the tyrosine kinase inhibitor RPI-1 on the human lung cancer cell lines H460 and N592, which express constitutively active Met. RPI-1-treated cells showed down-regulation of Met activation and expression, inhibition of HGF/Met-dependent downstream signaling involving AKT, signal transducers and activators of transcription 3 and paxillin, as well as a reduced expression of the proangiogenic factors vascular endothelial growth factor and basic fibroblast growth factor. Cell growth in soft agar of H460 cells was strongly reduced in the presence of the drug. Furthermore, RPI-1 inhibited both spontaneous and HGF-induced motility/invasiveness of both H460 and human endothelial cells. Targeting of Met signaling by alternative methods (Met small interfering RNA and anti-phosphorylated Met antibody intracellular transfer) produced comparable biochemical and biological effects. Using the spontaneously metastasizing lung carcinoma xenograft H460, daily oral treatment with well-tolerated doses of RPI-1 produced a significant reduction of spontaneous lung metastases (−75%; P &lt; 0.001, compared with control mice). In addition, a significant inhibition of angiogenesis in primary s.c. tumors of treated mice was observed, possibly contributing to limit the development of metastases. The results provide preclinical evidence in support of Met targeting pharmacologic approach as a new option for the control of tumor metastatic dissemination. [Mol Cancer Ther 2006;5(9):2388–97]
Detecting recombination in evolving nucleotide sequences
Authors: Chan Cheong Xin , Beiko Robert G , Ragan Mark A 
Published: September 2006

Abstract

Background
Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. These recombination events can be obscured by subsequent residue substitutions, which consequently complicate their detection. While there are many algorithms for the identification of recombination events, little is known about the effects of subsequent substitutions on the accuracy of available recombination-detection approaches.

Results
We assessed the effect of subsequent substitutions on the detection of simulated recombination events within sets of four nucleotide sequences under a homogeneous evolutionary model. The amount of subsequent substitutions per site, prior evolutionary history of the sequences, and reciprocality or non-reciprocality of the recombination event all affected the accuracy of the recombination-detecting programs examined. Bayesian phylogenetic-based approaches showed high accuracy in detecting evidence of recombination event and in identifying recombination breakpoints. These approaches were less sensitive to parameter settings than other methods we tested, making them easier to apply to various data sets in a consistent manner.

Conclusion
Post-recombination substitutions tend to diminish the predictive accuracy of recombination-detecting programs. The best method for detecting recombined regions is not necessarily the most accurate in identifying recombination breakpoints. For difficult detection problems involving highly divergent sequences or large data sets, different types of approach can be run in succession to increase efficiency, and can potentially yield better predictive accuracy than any single method used in isolation.
Comparison of methods for genomic localization of gene trap sequences
Authors: Harper Courtney A , Huang Conrad C , Stryke Doug , Kawamoto Michiko , Ferrin Thomas E , Babbitt Patricia C 
Published: September 2006

Abstract

Background
Gene knockouts in a model organism such as mouse provide a valuable resource for the study of basic biology and human disease. Determining which gene has been inactivated by an untargeted gene trapping event poses a challenging annotation problem because gene trap sequence tags, which represent sequence near the vector insertion site of a trapped gene, are typically short and often contain unresolved residues. To understand better the localization of these sequences on the mouse genome, we compared stand-alone versions of the alignment programs BLAT, SSAHA, and MegaBLAST. A set of 3,369 sequence tags was aligned to build 34 of the mouse genome using default parameters for each algorithm. Known genome coordinates for the cognate set of full-length genes (1,659 sequences) were used to evaluate localization results.

Results
In general, all three programs performed well in terms of localizing sequences to a general region of the genome, with only relatively subtle errors identified for a small proportion of the sequence tags. However, large differences in performance were noted with regard to correctly identifying exon boundaries. BLAT correctly identified the vast majority of exon boundaries, while SSAHA and MegaBLAST missed the majority of exon boundaries. SSAHA consistently reported the fewest false positives and is the fastest algorithm. MegaBLAST was comparable to BLAT in speed, but was the most susceptible to localizing sequence tags incorrectly to pseudogenes.

Conclusion
The differences in performance for sequence tags and full-length reference sequences were surprisingly small. Characteristic variations in localization results for each program were noted that affect the localization of sequence at exon boundaries, in particular.
Plasma membrane calcium ATPase (PMCA4): A housekeeper for RT-PCR relative quantification of polytopic membrane proteins
Authors: Calcagno Anna Maria , Chewning Katherine J , Wu Chung-Pu , Ambudkar Suresh V 
Published: September 2006

Abstract

Background
Although relative quantification of real-time RT-PCR data can provide valuable information, one limitation remains the selection of an appropriate reference gene. No one gene has emerged as a universal reference gene and much debate surrounds some of the more commonly used reference genes, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). At this time, no gene encoding for a plasma membrane protein serves as a reference gene, and relative quantification of plasma membrane proteins is performed with genes encoding soluble proteins, which differ greatly in quantity and in targeting and trafficking from plasma membrane proteins. In this work, our aim was to identify a housekeeping gene, ideally one that codes for a plasma membrane protein, whose expression remains the same regardless of drug treatment and across a wide range of tissues to be used for relative quantification of real-time RT-PCR data for ATP binding cassette (ABC) plasma membrane transporters.

Results
In studies evaluating the expression levels of two commonly used reference genes coding for soluble proteins and two genes coding for membrane proteins, one plasma membrane protein, plasma membrane calcium-ATPase 4 (PMCA4), was comparable to the two reference genes already in use. In addition, PMCA4 expression shows little variation across eight drug-treated cell lines and was found to be superior to GAPDH and HPRT1, commonly used reference genes. Finally, we show PMCA4 used as a reference gene for normalizing ABC transporter expression in a drug-resistant lung carcinoma cell line.

Conclusion
We have found that PMCA4 is a good housekeeping gene for normalization of gene expression for polytopic membrane proteins including transporters and receptors.
Bowel cancer screening in England: a qualitative study of GPs' attitudes and information needs
Authors: Woodrow Chris , Rozmovits Linda , Hewitson Paul , Rose Peter , Austoker Joan , Watson Eila 
Published: September 2006

Abstract

Background
The National Health Service Bowel Cancer Screening Programme is to be introduced in England during 2006. General Practitioners are a potentially important point of contact for participants throughout the screening process. The aims of the study were to examine GPs' attitudes and information needs with regard to bowel cancer screening, with a view to developing an information pack for primary care teams that will be circulated prior to the introduction of the programme.

Methods
32 GPs participated in semi-structured telephone interviews. 18 of these had participated in the English Bowel Screening Pilot, and 14 had not. Interviews covered attitudes towards the introduction of the Bowel Cancer Screening Programme, expected or actual increases in workload, confidence in promoting informed choice, and preferences for receiving information about the programme.

Results
GPs in the study were generally positive about the introduction of the Bowel Cancer Screening Programme. A number of concerns were identified by GPs who had not taken part in the pilot programme, particularly relating to patient welfare, patient participation, and increased workload. GPs who had taken part in the pilot reported holding similar concerns prior to their involvement. However, in many cases these concerns were not confirmed through GPs experiences with the pilot. A number of specific information needs were identified by GPs to enable them to provide a supportive role to participants in the programme.

Conclusion
The study has found considerable GP support for the introduction of the new Bowel Cancer Screening Programme. Nonetheless, GPs hold some significant reservations regarding the programme. It is important that the information needs of GPs and other members of the primary care team are addressed prior to the roll-out of the programme so they are equipped to promote informed choice and provide support to patients who consult them with queries regarding screening.
Overweight, physical activity, tobacco and alcohol consumption in a cross-sectional random sample of German adults
Authors: Haenle Mark M , Brockmann Stefan O , Kron Martina , Bertling Ursula , Mason Richard A , Steinbach Gerald , Boehm Bernhard O , Koenig Wolfgang , Kern Peter , Piechotowski Isolde , Kratzer Wolfgang ,   the EMIL-Study group
Published: September 2006

Abstract

Background
There is a current paucity of data on the health behaviour of non-selected populations in Central Europe. Data on health behaviour were collected as part of the EMIL study which investigated the prevalence of infection with Echinococcus multilocularis and other medical conditions in an urban German population.

Methods
Participating in the present study were 2,187 adults (1,138 females [52.0%]; 1,049 males [48.0%], age: 18–65 years) taken from a sample of 4,000 persons randomly chosen from an urban population. Data on health behaviour like physical activity, tobacco and alcohol consumption were obtained by means of a questionnaire, documentation of anthropometric data, abdominal ultrasound and blood specimens for assessment of chemical parameters.

Results
The overall rate of participation was 62.8%. Of these, 50.3% of the adults were overweight or obese. The proportion of active tobacco smokers stood at 30.1%. Of those surveyed 38.9% did not participate in any physical activity. Less than 2 hours of leisure time physical activity per week was associated with female sex, higher BMI (Body Mass Index), smoking and no alcohol consumption. Participants consumed on average 12 grams of alcohol per day. Total cholesterol was in 62.0% (>5.2 mmol/l) and triglycerides were elevated in 20.5% (≥ 2.3 mmol/l) of subjects studied. Hepatic steatosis was identified in 27.4% of subjects and showed an association with male sex, higher BMI, higher age, higher total blood cholesterol, lower HDL, higher triglycerides and higher ALT.

Conclusion
This random sample of German urban adults was characterised by a high prevalence of overweight and obesity. This and the pattern of alcohol consumption, smoking and physical activity can be considered to put this group at high risk for associated morbidity and underscore the urgent need for preventive measures aimed at reducing the significantly increased health risk.
Knee loading stimulates cortical bone formation in murine femurs
Authors: Zhang Ping , Su Min , Tanaka Shigeo M , Yokota Hiroki 
Published: September 2006

Abstract

Background
Bone alters its architecture and mass in response to the mechanical environment, and thus varying loading modalities have been examined for studying load-driven bone formation. The current study aimed to evaluate the anabolic effects of knee loading on diaphyseal cortical bone in the femur.

Methods
Using a custom-made piezoelectric loader, 0.5-N loads were laterally applied to the left knee of C57/BL/6 mice at 5, 10, 15, and 20 Hz for 3 minutes per day for 3 consecutive days. Animals were sacrificed for examination 13 days after the last loading. The contralateral femur was used as a non-loading control, and the statistical significance of loading effects was evaluated with p < 0.05.

Results
Although diaphyseal strains were measured as small as 12 μstrains, bone histomorphometry clearly demonstrated frequency-dependent enhancement of bone formation. Compared to a non-loading control, bone formation on the periosteal surface was significantly enhanced. The loading at 15 Hz was most effective in elevating the mineralizing surface (1.7 x; p < 0.05), mineral apposition rate (1.4 x; p < 0.001), and bone formation rate (2.4 x; p < 0.01). The loading at 10 Hz elevated the mineralizing surface (1.4 x; p < 0.05), mineral apposition rate (1.3 x; p < 0.01), and bone formation rate (1.8 x; p < 0.05). The cross-sectional cortical area and the cortical thickness in the femoral diaphysis were significantly increased by loading at 10 Hz (both 9%) and 15 Hz (12% and 13%, respectively).

Conclusion
The results support the anabolic effects of knee loading on diaphyseal cortical bone in the femur with small in situ strain, and they extend our knowledge on the interplay between bone and joints. Strengthening the femur contributes to preventing femoral fractures, and the discovery about the described knee loading might provide a novel strategy to strengthen osteoporotic bones. Further analyses are required to understand the biophysical and molecular mechanism behind knee loading.
The expression level of frog relaxin mRNA (fRLX), in the testis of Rana esculenta, is influenced by testosterone
Authors: De Rienzo Gianluca , Aniello Francesco , Branno Margherita , Izzo Gaia , Minucci Sergio 
Published: September 2006

SUMMARY
Frog relaxin (fRLX) belongs to the relaxin/insulin gene family present in the testis of Rana esculenta and is specifically expressed by Leydig cells. Since the expression of fRLX transcript changes during the reproductive cycle and is more abundant when circulating levels of androgens are relatively high, we investigated the effect(s) of testosterone and its antagonist (cyproterone acetate, CPA) on its expression pattern, in the testis of the frog Rana esculenta. Results from in vivoand in vitro experiments demonstrate that testosterone strongly induces a significant increase of fRLX mRNA expression in frog testes and, this effect is counteracted by CPA, supporting the existence of intratesticular (autocrine/paracrine) mechanisms of action. Interestingly, in both the control and testosterone-treated testes, fRLX mRNA expression was markedly decreased 24 h post-treatment, as compared to that measured at 2 h and 8 h post-treatment, suggesting that factor(s), other than testosterone, may act(s) in controlling its expression. In addition, RT-PCR analysis and in situ hybridization performed on frog testis injected with CPA for 15 days, on alternate days, showed a strong decrease of fRLX expression, suggesting that CPA counteracts the effect of testosterone on fRLX expression. Taken together our results strongly indicate that changes in the production, by the Leydig cells, of both testosterone and fRLX may represent a marker for the study of Leydig cell activity in the testis of the frog Rana esculenta.
Dietary acidification enhances phosphorus digestibility but decreases H+/K+-ATPase expression in rainbow trout
Authors: Sugiura Shozo H. , Roy Prabir K. , Ferraris Ronaldo P. 
Published: September 2006

SUMMARY
Oxynticopeptic cells of fish stomach are thought to secrete less acid than the specialized parietal cells of mammalian stomach. Gastric acidity, however,has not been directly compared between fish and mammals. We therefore fed rainbow trout and rats the same meal, and found that the lowest postprandial pH of trout stomach was 2.7, which was only transiently sustained for 1 h,whereas that of rat stomach was 1.3, which was sustained for 3 h. Postprandial pH of the small intestine was slightly higher in trout (∼8.0) than in rats(∼7.6), but pH of the large intestine was similar (∼8.0). Addition of acids to fish feeds, in an attempt to aid the weak acidity of fish stomach,has been known to improve phosphorus digestibility, but its physiological effect on fish stomach is not known. Exogenous acids did improve phosphorus digestibility but also decreased steady-state mRNA expression of trout H+/K+-ATPase (ATP4A, the proton pump) as well as Na+/bicarbonate cotransporter (NBC), and had no effect on gastrin-like mRNA and somastostatin (SST) mRNA abundance. Gastrin-like mRNA and SST-2 mRNA were equally distributed between corpus and antrum. ATP4A mRNA and NBC mRNA were in the corpus, whereas SST-1 mRNA was in the antrum. Trout gastrin-like EST had modest homology to halibut and pufferfish gastrin,whereas trout ATP4A mRNA had ≥95% amino acid homology with mammalian, Xenopus and flounder ATP4A. Although ATP4A seems highly conserved among vertebrates, gastric acidity is much less in trout than in rats,explaining the low digestibility of bone phosphorus, abundant in fish diets. Dietary acidification does not reduce acidity enough to markedly improve phosphorus digestibility, perhaps because exogenous acids may inhibit endogenous acid production.
Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf killifish,Fundulus grandis
Authors: Martínez Mery L. , Landry Christie , Boehm Ryan , Manning Steve , Cheek Ann Oliver , Rees Bernard B. 
Published: September 2006

SUMMARYThe goal of the current study was to generate a comprehensive, multi-tissue perspective of the effects of chronic hypoxic exposure on carbohydrate metabolism in the Gulf killifish Fundulus grandis. Fish were held at approximately 1.3 mg l-1 dissolved oxygen (∼3.6 kPa) for 4 weeks, after which maximal activities were measured for all glycolytic enzymes in four tissues (white skeletal muscle, liver, heart and brain), as well as for enzymes of glycogen metabolism (in muscle and liver) and gluconeogenesis(in liver). The specific activities of enzymes of glycolysis and glycogen metabolism were strongly suppressed by hypoxia in white skeletal muscle, which may reflect decreased energy demand in this tissue during chronic hypoxia. In contrast, several enzyme specific activities were higher in liver tissue after hypoxic exposure, suggesting increased capacity for carbohydrate metabolism. Hypoxic exposure affected fewer enzymes in heart and brain than in skeletal muscle and liver, and the changes were smaller in magnitude, perhaps due to preferential perfusion of heart and brain during hypoxia. The specific activities of some gluconeogenic enzymes increased in liver during long-term hypoxic exposure, which may be coupled to increased protein catabolism in skeletal muscle. These results demonstrate that when intact fish are subjected to prolonged hypoxia, enzyme activities respond in a tissue-specific fashion reflecting the balance of energetic demands, metabolic role and oxygen supply of particular tissues. Furthermore, within glycolysis, the effects of hypoxia varied among enzymes, rather than being uniformly distributed among pathway enzymes.
Feeding and digestion in low salinity in an osmoconforming crab, Cancer gracilis II. Gastric evacuation and motility
Authors: McGaw Iain J. 
Published: September 2006

SUMMARY
Gastric evacuation and gut contraction rates were followed in the graceful crab Cancer gracilis during exposure to low salinity. Crabs were fed a radio-opaque meal and then exposed to 100% seawater (SW), 80%SW or 60%SW;passage of digesta was followed using a fluoroscope. Exposure to low salinity increased the time for food passage through the gut system. Times for emptying of the foregut, midgut and hindgut varied in a dose-dependent manner. In the lowest salinity, crabs regurgitated food from the foregut after approximately 6 h. This may act as a protective response, clearing the gut and avoiding subsequent increases in metabolism associated with digestion. Contraction rate of the cardiac stomach and gastric mill was sporadic and there was no significant change with salinity. In contrast, contractions of the pyloric region were more constant and rapid. Pyloric contractions decreased at each salinity within 2-4 h after feeding. Contraction rates of the pyloric chamber were significantly lower in 60%SW compared with 100%SW and 80%SW. During a salinity cycle there was also slowing of gut contractions and food passage through the gut system. Pre-treatment levels were only regained slowly when the animals were returned to 100%SW. Cancer gracilis was able to slow digestion during low salinity exposure, which may spare resources for other systems. However, the crabs could not halt digestion completely and may be committed to protein synthesis once intracellular digestion has begun.
Well Performance With Operating Limits Under Reservoir and Completion Uncertainties
Authors: Wehunt C. D. 
Published: September 2006

SummaryThis paper shows how to evaluate well performance under conditions of reservoir and completion uncertainty while also considering the impact of completion decisions and operating constraints. This topic is important because it can help to reconcile the often large gap between short-term deliverability and reliable and sustainable performance.Table 1 presents a list of operating constraints, and this paper includes examples regarding the application of some of the constraints. This table also includes consideration for the type of surveillance that is needed to apply the constraints. Discussion within the paper shows that the most relevant types of operating constraints are often not being used and also addresses appropriate operating limits for completions with sand control.Completion selection and design influence operating constraints. Examples within the paper illustrate methods to determine appropriate operating constraints. The examples also demonstrate the potential advantage of frac-packed completions or long horizontal completions with regard to preventing fines movement and increasing the longevity of both the completion equipment and the productivity.To aid with probabilistic performance forecasting, the paper includes a tabulation of published skin values including some permeability data.