bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic signature of breast cancer cell line MCF-7: profiling of modified nucleosides via LC-IT MS coupling
Authors: Bullinger Dino , Neubauer Hans , Fehm Tanja , Laufer Stefan , Gleiter Christoph H , Kammerer Bernd 
Published: November 2007

Abstract

Background
Cancer, like other diseases accompanied by strong metabolic disorders, shows characteristic effects on cell turnover rate, activity of modifying enzymes and DNA/RNA modifications, resulting also in elevated amounts of excreted modified nucleosides. For a better understanding of the impaired RNA metabolism in breast cancer cells, we screened these metabolites in the cell culture supernatants of the breast cancer cell line MCF-7 and compared it to the human mammary epithelial cells MCF-10A. The nucleosides were isolated and analyzed via 2D-chromatographic techniques: In the first dimension by cis-diol specific boronate affinity extraction and subsequently by reversed phase chromatography coupled to an ion trap mass spectrometer.

Results
Besides the determination of ribonucleosides, additional compounds with cis-diol structure, deriving from cross-linked biochemical pathways, like purine-, histidine- and polyamine metabolism were detected. In total, 36 metabolites were identified by comparison of fragmentation patterns and retention time. Relation to the internal standard isoguanosine yielded normalized area ratios for each identified compound and enabled a semi-quantitative metabolic signature of both analyzed cell lines.
13 of the identified 26 modified ribonucleosides were elevated in the cell culture supernatants of MCF-7 cells, with 5-methyluridine, N
2,N
2,7-trimethylguanosine, N
6-methyl-N
6-threonylcarbamoyladenosine and 3-(3-aminocarboxypropyl)-uridine showing the most significant differences. 1-ribosylimidazole-4-acetic acid, a histamine metabolite, was solely found in the supernatants of MCF-10A cells, whereas 1-ribosyl-4-carboxamido-5-aminoimidazole and S-adenosylmethionine occurred only in supernatants of MCF-7 cells.

Conclusion
The obtained results are discussed against the background of pathological changes in cell metabolism, resulting in new perspectives for modified nucleosides and related metabolites as possible biomedical markers for breast carcinoma in vivo.
HCCR-1, a novel oncogene, encodes a mitochondrial outer membrane protein and suppresses the UVC-induced apoptosis
Authors: Cho Goang-Won , Shin Seung Min , Kim Hyun Kee , Ha Seon-Ah , Kim Sanghee , Yoon Joo-Hee , Hur Soo Young , Kim Tae Eung , Kim Jin Woo 
Published: November 2007

Abstract

Background
The Human cervical cancer oncogene (HCCR-1) has been isolated as a human oncoprotein, and has shown strong tumorigenic features. Its potential role in tumorigenesis may result from a negative regulation of the p53 tumor suppressor gene.

Results
To investigate the biological function of HCCR-1 in the cell, we predicted biological features using bioinformatic tools, and have identified a LETM1 homologous domain at position 75 to 346 of HCCR-1. This domain contains proteins identified from diverse species predicted to be mitochondrial proteins. Fluorescence microscopy and fractionation experiments showed that HCCR-1 is located in mitochondria in the COS-7, MCF-7 and HEK/293 cell lines, and subcompartamentally at the outer membrane in the HEK/293 cell line. The topological structure was revealed as the NH2-terminus of HCCR-1 oriented toward the cytoplasm. We also observed that the D1-2 region, at position 1 to 110 of HCCR-1, was required and sufficient for posttranslational mitochondrial import. The function of HCCR-1 on mitochondrial membrane is to retard the intrinsic apoptosis induced by UVC and staurosporine, respectively.

Conclusion
Our experiments show the biological features of HCCR-1 in the cell, and suggest that uncontrolled expression of HCCR-1 may cause mitochondrial dysfunction that can result in resisting the UVC or staurosporine-induced apoptosis and progressing in the tumor formation.
An additional human chromosome 21 causes suppression of neural fate of pluripotent mouse embryonic stem cells in a teratoma model
Authors: Mensah Afua , Mulligan Claire , Linehan Jackie , Ruf Sandra , O'Doherty Aideen , Grygalewicz Beata , Shipley Janet , Groet Juergen , Tybulewicz Victor , Fisher Elizabeth , Brandner Sebastian , Nizetic Dean 
Published: November 2007

Abstract

Background
Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21), is the most common genetic cause of mental retardation in humans. Among complex phenotypes, it displays a number of neural pathologies including smaller brain size, reduced numbers of neurons, reduced dendritic spine density and plasticity, and early Alzheimer-like neurodegeneration. Mouse models for DS show behavioural and cognitive defects, synaptic plasticity defects, and reduced hippocampal and cerebellar neuron numbers. Early postnatal development of both human and mouse-model DS shows the reduced capability of neuronal precursor cells to generate neurons. The exact molecular cause of this reduction, and the role played by increased dosage of individual HSA21 genes, remain unknown.

Results
We have subcutaneously injected mouse pluripotent ES cells containing a single freely segregating supernumerary human chromosome 21 (HSA21) into syngeneic mice, to generate transchromosomic teratomas. Transchromosomic cells and parental control cells were injected into opposite flanks of thirty mice in three independent experiments. Tumours were grown for 30 days, a time-span equivalent to combined intra-uterine, and early post-natal mouse development. When paired teratomas from the same animals were compared, transchromosomic tumours showed a three-fold lower percentage of neuroectodermal tissue, as well as significantly reduced mRNA levels for neuron specific (Tubb3) and glia specific (Gfap) genes, relative to euploid controls. Two thirds of transchromosomic tumours also showed a lack of PCR amplification with multiple primers specific for HSA21, which were present in the ES cells at the point of injection, thus restricting a commonly retained trisomy to less than a third of HSA21 genes.

Conclusion
We demonstrate that a supernumerary chromosome 21 causes Inhibition of Neuroectodermal DIfferentiation (INDI) of pluripotent ES cells. The data suggest that trisomy of less than a third of HSA21 genes, in two chromosomal regions, might be sufficient to cause this effect.
The oxidative stress adaptor p66Shc is required for permanent embryo arrest in vitro
Authors: Favetta Laura A , Madan Pavneesh , Mastromonaco Gabriela F , St John Elizabeth J , King W Allan , Betts Dean H 
Published: November 2007

Abstract

Background
Excessive developmental failure occurs during the first week of in vitro embryo development due to elevated levels of cell death and arrest. We hypothesize that permanently arrested embryos enter a stress-induced "senescence-like" state that is dependent on the oxidative stress-adaptor and lifespan determinant protein p66Shc. The aim of this study was to selectively diminish p66Shc gene expression in bovine oocytes and embryos using post-transcriptional gene silencing by RNA-mediated interference to study the effects of p66Shc knockdown on in vitro fertilized bovine embryos.

Results
Approximately 12,000–24,000 short hairpin (sh)RNAi molecules specific for p66Shc were microinjected into bovine germinal vesicle stage oocytes or zygotes. Experiments were comprised of a control group undergoing IVF alone and two groups microinjected with and without p66Shc shRNAi molecules prior to IVF. The amount of p66Shc mRNA quantified by Real Time PCR was significantly (P < 0.001) lowered upon p66Shc shRNAi microinjection. This reduction was selective for p66Shc mRNA, as both histone H2a and p53 mRNA levels were not altered. The relative signal strength of p66Shc immuno-fluorescence revealed a significant reduction in the number of pixels for p66Shc shRNAi microinjected groups compared to controls (P < 0.05). A significant decrease (P < 0.001) in the incidence of arrested embryos upon p66Shc shRNAi microinjection was detected compared to IVF and microinjected controls along with significant reductions (P < 0.001) in both cleavage divisions and blastocyst development. No significant differences in p66Shc mRNA levels (P = 0.314) were observed among the three groups at the blastocyst stage.

Conclusion
These results show that p66Shc is involved in the regulation of embryo development specifically in mediating early cleavage arrest and facilitating development to the blastocyst stage for in vitro produced bovine embryos.
Codon-triplet context unveils unique features of the Candida albicans protein coding genome
Authors: Moura Gabriela R , Lousado José P , Pinheiro Miguel , Carreto Laura , Silva Raquel M , Oliveira José L , Santos Manuel AS 
Published: November 2007

Abstract

Background
The evolutionary forces that determine the arrangement of synonymous codons within open reading frames and fine tune mRNA translation efficiency are not yet understood. In order to tackle this question we have carried out a large scale study of codon-triplet contexts in 11 fungal species to unravel associations or relationships between codons present at the ribosome A-, P- and E-sites during each decoding cycle.

Results
Our analysis unveiled high bias within the context of codon-triplets, in particular strong preference for triplets of identical codons. We have also identified a surprisingly large number of codon-triplet combinations that vanished from fungal ORFeomes. Candida albicans exacerbated these features, showed an unbalanced tRNA population for decoding its pool of codons and used near-cognate decoding for a large set of codons, suggesting that unique evolutionary forces shaped the evolution of its ORFeome.

Conclusion
We have developed bioinformatics tools for large-scale analysis of codon-triplet contexts. These algorithms identified codon-triplets context biases, allowed for large scale comparative codon-triplet analysis, and identified rules governing codon-triplet context. They could also detect alterations to the standard genetic code.
Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli
Authors: Ubeda-Bañon Isabel , Novejarque Amparo , Mohedano-Moriano Alicia , Pro-Sistiaga Palma , de la Rosa-Prieto Carlos , Insausti Ricardo , Martinez-Garcia Fernando , Lanuza Enrique , Martinez-Marcos Alino 
Published: November 2007

Abstract

Background
Vertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae). The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja.

Results
Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections.

Conclusion
The present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse.
An exploration of the use of simple statistics to measure consensus and stability in Delphi studies
Authors: Holey Elizabeth A , Feeley Jennifer L , Dixon John , Whittaker Vicki J 
Published: November 2007

Abstract

Background
The criteria for stopping Delphi studies are often subjective. This study aimed to examine whether consensus and stability in the Delphi process can be ascertained by descriptive evaluation of trends in participants' views.

Methods
A three round email-based Delphi required participants (n = 12) to verify their level of agreement with 8 statements, write comments on each if they considered it necessary and rank the statements for importance. Each statement was analysed quantitatively by the percentage of agreement ratings, importance rankings and the amount of comments made for each statement, and qualitatively using thematic analysis. Importance rankings between rounds were compared by calculating Kappa values to observe trends in how the process impacts on subject's views.

Results
Evolution of consensus was shown by increase in agreement percentages, convergence of range with standard deviations of importance ratings, and a decrease in the number of comments made. Stability was demonstrated by a trend of increasing Kappa values.

Conclusion
Following the original use of Delphi in social sciences, Delphi is suggested to be an effective way to gain and measure group consensus in healthcare. However, the proposed analytical process should be followed to ensure maximum validity of results in Delphi methodology for improved evidence of consensual decision-making.
Verification of the formulation and efficacy of Danggui Buxue Tang (a decoction of Radix Astragali and Radix Angelicae Sinensis): an exemplifying systematic approach to revealing the complexity of Chinese herbal medicine formulae
Authors: Gao Qiutao , Li Jun , Cheung Jerry Ka Hei , Duan Jinao , Ding Anwei , Cheung Anna Wing Han , Zhao Kuijun , Li Winnie Zhuoming , Dong Tina Tingxia , Tsim Karl Wah Keung 
Published: November 2007

Abstract
This article exemplifies a systematic approach to revealing the complexity of Chinese herbal medicine formulae through three levels of scientific research: standardization of herbs, verification of ancient formulae and mechanism studies. We use Danggui Buxue Tang (DBT) as an example for this approach. Among thousands of traditional Chinese medicine herbal formulae, almost all of which consist of multiple herbs, DBT is one of the simplest. Containing only two herbs, namely Radix Astragali (RA) and Radix Angelicae Sinensis (RAS), DBT is traditionally used to treat ailments in women. The weight ratio of RA to RAS in DBT was prescribed to be 5:1 as early as in 1247 AD. In addition to advanced chemical analysis of herbal constituents, DNA genotyping techniques have been developed for reliable standardization of RA and RAS. Chemical evaluation shows that main active constituents in DBT, including astragaloside IV, calycosin, formononetin and ferulic acid, were most abundant after extraction at the RA to RAS ratio of 5:1, whereas other tested RA to RAS ratios only gave sub-optimal levels of the active constituents. Biological evaluation indicates that bioactivities of DBT, e.g. immuno-modulatory, oesteotropic and estrogenic effects are also best exerted at the RA to RAS ratio of 5:1. Correlation analysis demonstrates statistically significant relationship between the tested chemical constituents and tested bioactivities. Up- and down-regulation of expression of some genes as potential biomarkers has been detected by using gene chip technology. This systematic approach on the basis of herbal standardization, chemical and biological verification and mechanism studies, as exemplified in this article, will be useful to reveal the complexity of not only DBT but also other Chinese medicine herbal formulae.
Cerebral haemodynamics and carbon dioxide reactivity during sepsis syndrome
Authors: Thees Christof , Kaiser Markus , Scholz Martin , Semmler Alexander , Heneka Michael T , Baumgarten Georg , Hoeft Andreas , Putensen Christian 
Published: November 2007

Abstract
Background
Most patients with sepsis develop potentially irreversible cerebral dysfunctions. It is yet not clear whether cerebral haemodynamics are altered in these sepsis patients at all, and to what extent. We hypothesized that cerebral haemodynamics and carbon dioxide reactivity would be impaired in patients with sepsis syndrome and pathological electroencephalogram patterns.

Methods
After approval of the institutional ethics committee, 10 mechanically ventilated patients with sepsis syndrome and pathological electroencephalogram patterns underwent measurements of cerebral blood flow and jugular venous oxygen saturation before and after reduction of the arterial carbon dioxide partial pressure by 0.93 ± 0.7 kPa iu by ypervent ilation. The cerebral capillary closing pressure was determined from transcranial Doppler measurements of the arterial blood flow of the middle cerebral artery and the arterial pressure curve. A t test for matched pairs was used for statistical analysis (P < 0.05).

Results
During stable mean arterial pressure and cardiac index, reduction of the arterial carbon dioxide partial pressure led to a significant increase of the capillary closing pressure from 25 ± 11 mmHg to 39 ± 15 mmHg (P < 0.001), with a consecutive decrease of blood flow velocity in the middle cerebral artery of 21.8 ± 4.8%/kPa (P < 0.001), of cerebral blood flow from 64 ± 29 ml/100 g/min to 39 ± 15 ml/100 g/min (P < 0.001) and of jugular venous oxygen saturation from 75 ± 8% to 67 ± 14% (P < 0.01).

Conclusion
In contrast to other experimental and clinical data, we observed no pathological findings in the investigated parameters of cerebral perfusion and oxygenation.
Phase I Study of Targeted Radioimmunotherapy for Leptomeningeal Cancers Using Intra-Ommaya 131-I-3F8
Authors: Kramer Kim , Humm John L. , Souweidane Mark M. , Zanzonico Pat B. , Dunkel Ira J. , Gerald William L. , Khakoo Yasmin , Yeh Samuel D. , Yeung Henry W. , Finn Ronald D. , Wolden Suzanne L. , Larson Steven M. , Cheung Nai-Kong V. 
Published: November 2007

Purpose Tumors metastasizing to the CNS and leptomeninges (LM) are associated with significant mortality. We tested the toxicity, pharmacokinetics, and dosimetry of intraventricular iodine-131–labeled monoclonal antibody 3F8 (131I-3F8) targeting GD2-positive CNS/LM disease in a phase I clinical trial. Patients and Methods Adequate CSF flow was determined by pretreatment indium-111-DTPA studies. Fifteen patients received a tracer (1 to 2 mCi) and therapeutic injection (10 to 20 mCi) of intra-Ommaya 131I-3F8. 131I-3F8 pharmacokinetics were studied by serial CSF and blood samplings. Dosimetry was based on pharmacokinetics and region of interest (ROI) analyses on whole-body gamma camera scans. Tumor response was determined by clinical, radiographic, and cytologic criteria. Results Total absorbed CSF dose was 1.12 to 13.00 Gy by sampling and 1.00 to 13.70 Gy by ROI data. Average dosimetry ratio (Gy/mCi) of the therapy/tracer administration was 0.88 (± 0.58) and 1.08 (± 0.66) based on CSF pharmacokinetics and ROI analysis, respectively. CSF half-life by sampling was 3 to 12.9 hours. Toxicities included self-limited headache, fever, and vomiting. Dose-limiting toxicity was reached at the 20-mCi dose, when transient elevations in intracranial pressure and chemical meningitis were seen. Three of 13 assessable patients achieved objective radiographic and/or cytologic responses. No late toxicities have been seen in two patients who remain in remission off therapy for more than 3.5 years. Conclusion Intra-Ommaya 131I-3F8 was generally well tolerated; the maximum-tolerated dose was 10 mCi. A high CSF-to-blood ratio was achieved. Tracer studies reliably predicted the therapeutic dose to the CSF. Radioimmunoconjugates targeting GD2 may have clinical utility in the treatment of CNS/LM malignancies.
River Restoration Effects on Steelhead Populations in the Manistee River, Michigan: Analysis Using an Individual‐Based Model
Authors: Tyler Jeffrey A. , Rutherford Edward S. 
Published: November 2007

AbstractThe Manistee River, Michigan, watershed includes two dams as well as residential and agricultural development, and the river itself contains a sizeable population of steelhead Oncorhynchus mykiss that supports a valuable recreational fishery. Restoration of the Manistee River and its flow regime may improve steelhead habitat and the fishery. We developed an individual‐based model of steelhead in the Manistee River to assess the population effects of changes in the number of spawners, water discharge from Tippy Dam, and water temperature. The model follows steelhead from spring spawning to the end of the growing season in early fall and depicts the river environment as a series of cells that vary in dimension, water velocity, and substrate. Simulated water discharge, temperature, and prey availability changed daily based on observations from Tippy Dam. Empirically based models describe individual steelhead fry and parr foraging and growth. In the model, steelhead select habitats and maximize individual fitness while accounting for dominance and the availability of feeding territories. We calibrated the model to replicate fish growth, mortality, and population size. Simulation experiments manipulated the number of spawning females, water discharge, and water temperature. The results suggest that Manistee River steelhead incur density limitations in the fry and parr stages and that water discharge and temperature changes affect the number and biomass of parr. Increasing river discharge negatively affected parr numbers and weight. Decreasing maximum midsummer temperature increased parr numbers and weight when the change was large, but otherwise had little effect. These results indicate that restoration of the natural flow regime in the Manistee River will probably increase the quality of the habitat for steelhead but that density limitations in the fry and parr stages may ultimately limit population growth.
Critical Thinking and Reading
Authors: Mendelman Lisa 
Published: November 2007

From freshman composition courses to high school exit exams, the term critical thinking is everywhere. The educationally ubiquitous term has been defined as criticism that combines research, knowledge of historical context, and balanced judgment.In theory then, critical thinking should be taught in virtually every course in the humanities. In practice, however, my years as a high school English teacher, as well as my decades on the other side of the desk, have proven that the lofty title is a gross misnomer, conveniently obscuring the fact that the majority of our schools fail to teach critical thinking and, as a result, the majority of our populace does not practice it.
What Can We Learn From the Word Writing CAFÉ?
Authors: Bromley Karen , Vandenberg Amy , White Jennifer 
Published: November 2007

Guided reading is an important component of a comprehensive literacy program. Using this approach to reading instruction is beneficial to all students, including English‐language learners (ELLs). While guided reading is generally used in the early elementary grades, this approach is recommended for ELLs of all ages when appropriate methods and materials are used. Teachers can modify guided reading to better meet the literacy and second language (L2) learning needs of ELLs.Building on previous work in the area of guided reading and L2 reading instruction, this article describes guided‐reading modifications for ELLs, integrating reading, writing, listening, and speaking to build the four language skills. A lesson‐planning guide and examples are provided for teachers who are facing the challenge of providing language and literacy instruction to students learning to read in their L2.