bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of the oxidative pentose phosphate pathway and gluconeogenesis in anaerobically growing xylose-utilizing Saccharomyces cerevisiae
Authors: Runquist David , Hahn-Hägerdal Bärbel , Bettiga Maurizio 
Published: September 2009

Abstract

Background
Fermentation of xylose to ethanol has been achieved in S. cerevisiae by genetic engineering. Xylose utilization is however slow compared to glucose, and during anaerobic conditions addition of glucose has been necessary for cellular growth. In the current study, the xylose-utilizing strain TMB 3415 was employed to investigate differences between anaerobic utilization of glucose and xylose. This strain carried a xylose reductase (XYL1 K270R) engineered for increased NADH utilization and was capable of sustained anaerobic growth on xylose as sole carbon source. Metabolic and transcriptional characterization could thus for the first time be performed without addition of a co-substrate or oxygen.

Results
Analysis of metabolic fluxes showed that although the specific ethanol productivity was an order of magnitude lower on xylose than on glucose, product yields were similar for the two substrates. In addition, transcription analysis identified clear regulatory differences between glucose and xylose. Respiro-fermentative metabolism on glucose during aerobic conditions caused repression of cellular respiration, while metabolism on xylose under the same conditions was fully respiratory. During anaerobic conditions, xylose repressed respiratory pathways, although notably more weakly than glucose. It was also observed that anaerobic xylose growth caused up-regulation of the oxidative pentose phosphate pathway and gluconeogenesis, which may be driven by an increased demand for NADPH during anaerobic xylose catabolism.

Conclusion
Co-factor imbalance in the initial twp steps of xylose utilization may reduce ethanol productivity by increasing the need for NADP+ reduction and consequently increase reverse flux in glycolysis.
Spatial trends of breast and prostate cancers in the United States between 2000 and 2005
Authors: Mandal Rakesh , St-Hilaire Sophie , Kie John G , Derryberry DeWayne 
Published: September 2009

Abstract

Background
Breast cancer in females and prostate cancer in males are two of the most common cancers in the United States, and the literature suggests that they share similar features. However, it is unknown whether the occurrence of these two cancers at the county level in the United States is correlated. We analyzed Caucasian age-adjusted county level average annual incidence rates for breast and prostate cancers from the National Cancer Institute and State Cancer Registries to determine whether there was a spatial correlation between the two conditions and whether the two cancers had similar spatial patterns.

Results
There was a significant correlation between breast and prostate cancers by county (r = 0.332, p < 0.001). This relationship was more pronounced when we performed a geographically-weighted regression (GWR) analysis (r = 0.552) adjusting for county unemployment rates. There was variation in the parameter estimates derived with the GWR; however, the majority of the estimates indicted a positive association. The strongest relationship between breast and prostate cancer was in the eastern parts of the Midwest and South, and the Southeastern U.S. We also observed a north-south pattern for both cancers with our cluster analyses. Clusters of counties with high cancer incidence rates were more frequently found in the North and clusters of counties with low incidence rates were predominantly in the South.

Conclusion
Our analyses suggest breast and prostate cancers cluster spatially. This finding corroborates other studies that have found these two cancers share similar risk factors. The north-south distribution observed for both cancers warrants further research to determine what is driving this spatial pattern.
The rapamycin-regulated gene expression signature determines prognosis for breast cancer
Authors: Akcakanat Argun , Zhang Li , Tsavachidis Spiridon , Meric-Bernstam Funda 
Published: September 2009

Abstract

Background
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process or effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer.

Results
Colony formation and sulforhodamine B (IC50 < 1 nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset, RMI did not correlate with tumor size or lymph node status. High (>75th percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis, RMI (P = 0.029), tumor size (P = 0.015) and lymph node status (P = 0.001) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41). In the Wang dataset, RMI predicted time to disease relapse (P = 0.009).

Conclusion
Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment.
Blockage of transdifferentiation from fibroblast to myofibroblast in experimental ovarian cancer models
Authors: Yao Qin , Qu Xun , Yang Qifeng , Good David A , Dai Shuzhen , Kong Beihua , Wei Ming Q 
Published: September 2009

Abstract

Background
Tumour stromal myofibroblasts can promote tumour invasion. As these cells are genetically more stable than cancer cells, there has been enormous interest in developing targeted molecular therapies against them. Chloride intracellular channel 4 (CLIC4) and reactive oxygen species (ROS) have been linked with promoting stromal cell transdifferentiation in various cancers, but little is known of their roles in ovarian cancer. In this study, we examined the functional roles that both CLIC4 and ROS play in the process of ovarian cancer cell-stimulated or TGF-β1 induced fibroblast-to-myofibroblast transdifferentiation. We also examine whether it is possible to reverse such a process, with the aim of developing novel therapies against ovarian cancer by targeting activated transdifferentiated myofibroblasts.

Results
We demonstrate that TGF-β1 induced or CMSKOV3 activate transdifferentiated myofibroblasts (fibroblasts). These fibroblasts mimic "reactive" stromal myofibroblasts and demonstrate significant up-regulation of CLIC4 expression and increased level of ROS production. Blocking the production of ROS with an antioxidant consequently reduces the expression of CLIC4, and is accompanied by disappearance of α-smooth-muscle actin (α-SMA), a myofibroblast marker, suggesting ROS acts as a signalling molecule that promotes and enhances CLIC4 activities in the myofibroblast transdifferentiaton process. Down-regulation of CLIC4 with a generic agent or specific siRNA both significantly reduces the expression of factors related to the phenotypes and functions of myofibroblasts, such as α-SMA, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), thus reversing the myofibroblast phenotype back to fibroblasts. These results convincingly show that ROS and CLIC4 are responsible for TGF-β1 induced fibroblast-to-myofibroblast transdifferentiaton and down-regulation of both is sufficient to block transdifferentiated myofibroblasts.

Conclusion
Molecular targeting of ROS and CLIC4 has the potential to develop novel therapies for ovarian cancer.
2-DE analysis indicates that Acinetobacter baumannii displays a robust and versatile metabolism
Authors: Soares Nelson C , Cabral Maria P , Parreira José R , Gayoso Carmen , Barba Maria J , Bou Germán 
Published: September 2009

Abstract

Background

Acinetobacter baumannii is a nosocomial pathogen that has been associated with outbreak infections in hospitals. Despite increasing awareness about this bacterium, its proteome remains poorly characterised, however recently the complete genome of A. baumannii reference strain ATCC 17978 has been sequenced. Here, we have used 2-DE and MALDI-TOF/TOF approach to characterise the proteome of this strain.

Results
The membrane and cytoplasmatic protein extracts were analysed separately, these analyses revealed the reproducible presence of 239 and 511 membrane and cytoplamatic protein spots, respectively. MALDI-TOF/TOF characterisation identified a total of 192 protein spots (37 membrane and 155 cytoplasmatic) and revealed that the identified membrane proteins were mainly transport-related proteins, whereas the cytoplasmatic proteins were of diverse nature, although mainly related to metabolic processes.

Conclusion
This work indicates that A. baumannii has a versatile and robust metabolism and also reveal a number of proteins that may play a key role in the mechanism of drug resistance and virulence. The data obtained complements earlier reports of A. baumannii proteome and provides new tools to increase our knowledge on the protein expression profile of this pathogen.
c-Myc affects mRNA translation, cell proliferation and progenitor cell function in the mammary gland
Authors: Stoelzle Tina , Schwarb Patrick , Trumpp Andreas , Hynes Nancy E 
Published: September 2009

Abstract

Background

The oncoprotein c-Myc has been intensely studied in breast cancer and mouse mammary tumor models, but relatively little is known about the normal physiological role of c-Myc in the mammary gland. Here we investigated functions of c-Myc during mouse mammary gland development using a conditional knockout approach.

Results

Generation of c-myc

fl/fl
mice carrying the mammary gland-specific WAPiCre transgene resulted in c-Myc loss in alveolar epithelial cells starting in mid-pregnancy. Three major phenotypes were observed in glands of mutant mice. First, c-Myc-deficient alveolar cells had a slower proliferative response at the start of pregnancy, causing a delay but not a block of alveolar development. Second, while milk composition was comparable between wild type and mutant animals, milk production was reduced in mutant glands, leading to slower pup weight-gain. Electron microscopy and polysome fractionation revealed a general decrease in translational efficiency. Furthermore, analysis of mRNA distribution along the polysome gradient demonstrated that this effect was specific for mRNAs whose protein products are involved in milk synthesis. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed decreased levels of ribosomal RNAs and ribosomal protein-encoding mRNAs in mutant glands. Third, using the mammary transplantation technique to functionally identify alveolar progenitor cells, we observed that the mutant epithelium has a reduced ability to repopulate the gland when transplanted into NOD/SCID recipients.

Conclusion

We have demonstrated that c-Myc plays multiple roles in the mouse mammary gland during pregnancy and lactation. c-Myc loss delayed, but did not block proliferation and differentiation in pregnancy. During lactation, lower levels of ribosomal RNAs and proteins were present and translation was generally decreased in mutant glands. Finally, the transplantation studies suggest a role for c-Myc in progenitor cell proliferation and/or survival.
See related minireview by Evan et al: http://jbiol.com/content/8/8/77
Two matched filters and the evolution of mating signals in four species of cricket
Authors: Kostarakos Konstantinos , Hennig Matthias R , Römer Heiner 
Published: September 2009

Abstract

Background
Male field crickets produce pure-tone calling songs to attract females. Receivers are expected to have evolved a "matched filter" in the form of a tuned sensitivity for this frequency. In addition, the peripheral directionality of field crickets is sharply tuned as a result of a pressure difference receiver. We studied both forms of tuning in the same individuals of four species of cricket, where Gryllus bimaculatus and G. campestris are largely allopatric, whereas Teleogryllus oceanicus and T. commodus occur also sympatrically.

Results
The sharpness of the sensitivity filter is highest for T. commodus, which also exhibits low interindividual variability. Individual receivers may also vary strongly in the best frequency for directional hearing. In G. campestris, such best frequencies occur even at frequencies outside the range of carrier frequencies of males. Contrary to the predictions from the "matched filter hypothesis", in three of the four species the frequency optima of the two involved filters are not matched to each other, and the mismatch can amount to 1.2 kHz. The mean carrier frequency of the male population is between the frequency optima of both filters in three species. Only in T. commodus we found a match between both filters and the male carrier frequency.

Conclusion
Our results show that a mismatch between the sensitivity and directionality tuning is not uncommon in crickets, and an observed match (T. commodus) appears to be the exception rather than the rule. The data suggests that independent variation of both filters is possible. During evolution each sensory task may have been driven by independent constraints, and may have evolved towards its own respective optimum.
Induction of cell-cell fusion by ectromelia virus is not inhibited by its fusion inhibitory complex
Authors: Erez Noam , Paran Nir , Maik-Rachline Galia , Politi Boaz , Israely Tomer , Schnider Paula , Fuchs Pinhas , Melamed Sharon , Lustig Shlomo 
Published: September 2009

Abstract

Background
Ectromelia virus, a member of the Orthopox genus, is the causative agent of the highly infectious mousepox disease. Previous studies have shown that different poxviruses induce cell-cell fusion which is manifested by the formation of multinucleated-giant cells (polykaryocytes). This phenomenon has been widely studied with vaccinia virus in conditions which require artificial acidification of the medium.

Results
We show that Ectromelia virus induces cell-cell fusion under neutral pH conditions and requires the presence of a sufficient amount of viral particles on the plasma membrane of infected cells. This could be achieved by infection with a replicating virus and its propagation in infected cells (fusion "from within") or by infection with a high amount of virus particles per cell (fusion "from without"). Inhibition of virus maturation or inhibition of virus transport on microtubules towards the plasma membrane resulted in a complete inhibition of syncytia formation. We show that in contrast to vaccinia virus, Ectromelia virus induces cell-cell fusion irrespectively of its hemagglutination properties and cell-surface expression of the orthologs of the fusion inhibitory complex, A56 and K2. Additionally, cell-cell fusion was also detected in mice lungs following lethal respiratory infection.

Conclusion
Ectromelia virus induces spontaneous cell-cell fusion in-vitro and in-vivo although expressing an A56/K2 fusion inhibitory complex. This syncytia formation property cannot be attributed to the 37 amino acid deletion in ECTV A56.
Use of dried blood samples for monitoring hepatitis B virus infection
Authors: Lira Rosalia , Maldonado-Rodriguez Angelica , Rojas-Montes Othon , Ruiz-Tachiquin Martha , Torres-Ibarra Rocio , Cano-Dominguez Carlos , Valdez-Salazar Hilda , Gomez-Delgado Alejandro , Muñoz Onofre , Alvarez-Muñoz Ma-Teresa 
Published: September 2009

AbstractBackgroundHepatitis B virus (HBV) infection is a problem in several regions of the world with limited resources. Blood samples dried on filter paper (DBS) have been successfully used to diagnose and monitor several infectious diseases. In Mexico there is an urgent need for an affordable and easy sampling method for viral load (VL) testing and monitoring of chronic HBV infection. The purpose of this work was to validate the utility of DBS samples for monitoring HBV infection in patients from Mexico City.MethodsMatched samples of plasma and DBS on filter paper from 47 HBV infected patients from the Instituto Mexicano del Seguro Social (IMSS), were included. To evaluate the DNA stability and purity from DBS stored at different temperature conditions, samples from ten patients were stored at 4 degree, 25 degree, and 37 degree C for 7 days. After DBS elution and DNA extraction, the purity of these samples was determined measuring the O.D. rate 260/280. The DBS utility for molecular studies was assessed with PCR assays to amplify a 322 bp fragment from the "a" determinant region of the HBV "S" gene. The VL from all samples was determined to evaluate the correlation between plasma and DBS matched samples.ResultsThe quality of the DNA from DBS specimen is not adversely affected by storage at 4 degree, 25 degree and 37 degree C for up 7 days. Statistical ANOVA analyses did not show any significant difference. The same amplification efficiency was observed between DNA templates from samples stored at different temperatures. The Pearson correlation between the VL from DBS and plasma matched samples was 0.93 (p = 0.01). The SD was 1.48 for DBS vs.1.32 for Plasma, and an average of log10copies/mL of 5.32 vs. 5.53. ANOVA analysis did not show any statistically significant difference between the analyzed groups (p = 0.92).ConclusionThe results provide strong evidence that the isolation and quantification of DNA-HBV from DBS is a viable alternative for patient monitoring, and molecular characterization of the virus variants circulating in Mexico.
Multipathogen infections in hospitalized children with acute respiratory infections
Authors: Peng Dan , Zhao Dongchi , Liu Jingtao , Wang Xia , Yang Kun , Xicheng Hong , Li Yang , Wang Fubing 
Published: September 2009

Abstract

Background
To explore the epidemiologic and clinical features of, and interactions among, multipathogen infections in hospitalized children with acute respiratory tract infection (ARTI). A prospective study of children admitted with ARTI was conducted. Peripheral blood samples were analyzed by indirect immunofluorescence to detect respiratory agents including respiratory syncytial virus; adenovirus; influenza virus (Flu) types A and B; parainfluenza virus (PIV) types 1, 2, and 3; chlamydia pneumonia; and mycoplasma pneumonia. A medical history of each child was taken.

Results
Respiratory agents were detected in 164 (51.9%) of 316 children with ARTI. A single agent was identified in 50 (15.8%) children, and multiple agents in 114 (36.1%). Flu A was the most frequently detected agent, followed by Flu B. Coinfection occurred predominantly in August and was more frequent in children between 3 and 6 years of age. A significantly higher proportion of Flu A, Flu B, and PIV 1 was detected in samples with two or more pathogens per sample than in samples with a single pathogen.

Conclusion
Our study suggests that there is a high occurrence of multipathogen infections in children admitted with ARTI and that coinfection is associated with certain pathogens.
Transforming Boolean models to continuous models: methodology and application to T-cell receptor signaling
Authors: Wittmann Dominik M , Krumsiek Jan , Saez-Rodriguez Julio , Lauffenburger Douglas A , Klamt Steffen , Theis Fabian J 
Published: September 2009

Abstract

Background
The understanding of regulatory and signaling networks has long been a core objective in Systems Biology. Knowledge about these networks is mainly of qualitative nature, which allows the construction of Boolean models, where the state of a component is either 'off' or 'on'. While often able to capture the essential behavior of a network, these models can never reproduce detailed time courses of concentration levels.
Nowadays however, experiments yield more and more quantitative data. An obvious question therefore is how qualitative models can be used to explain and predict the outcome of these experiments.

Results
In this contribution we present a canonical way of transforming Boolean into continuous models, where the use of multivariate polynomial interpolation allows transformation of logic operations into a system of ordinary differential equations (ODE). The method is standardized and can readily be applied to large networks. Other, more limited approaches to this task are briefly reviewed and compared. Moreover, we discuss and generalize existing theoretical results on the relation between Boolean and continuous models. As a test case a logical model is transformed into an extensive continuous ODE model describing the activation of T-cells. We discuss how parameters for this model can be determined such that quantitative experimental results are explained and predicted, including time-courses for multiple ligand concentrations and binding affinities of different ligands. This shows that from the continuous model we may obtain biological insights not evident from the discrete one.

Conclusion
The presented approach will facilitate the interaction between modeling and experiments. Moreover, it provides a straightforward way to apply quantitative analysis methods to qualitatively described systems.
Puncture mechanics of cnidarian cnidocysts: a natural actuator
Authors: Oppegard Shawn C , Anderson Peter A , Eddington David T 
Published: September 2009

Abstract

Background
Cnidocysts isolated from cnidarian organisms are attractive as a drug-delivery platform due to their fast, efficient delivery of toxins. The cnidocyst could be utilized as the means to deliver therapeutics in a wearable drug-delivery patch. Cnidocysts have been previously shown to discharge upon stimulation via electrical, mechanical, and chemical pathways. Cnidocysts isolated from the Portuguese Man O' War jellyfish (Physalia physalis) are attractive for this purpose because they possess relatively long threads, are capable of puncturing through hard fish scales, and are stable for years.

Results
As a first step in using cnidocysts as a functional component of a drug delivery system, the puncture mechanics of the thread were characterized. Tentacle-contained cnidocysts were used as a best-case scenario due to physical immobilization of the cnidocysts within the tentacle. Ex vivo tentacle-contained cnidocysts from Physalia possessed an elastic modulus puncture threshold of approximately 1-2 MPa, based on puncture tests of materials with a gamut of hardness. Also, a method for inducing discharge of isolated cnidocysts was found, utilizing water as the stimulant. Preliminary lectin-binding experiments were performed using fluorophore-conjugated lectins as a possible means to immobilize the isolated cnidocyst capsule, and prevent reorientation upon triggering. Lectins bound homogeneously to the surface of the capsule, suggesting the lectins could be used for cnidocyst immobilization but not orientation.

Conclusion
Cnidocysts were found to puncture materials up to 1 MPa in hardness, can be discharged in a dry state using water as a stimulant, and bind homogeneously to lectins, a potential means of immobilization. The information gained from this preliminary work will aid in determining the materials and design of the patch that could be used for drug delivery.