bluuebunny/crossref_metadata_2025 huggingface dataset:
Ras and Its Signals Diffuse through the Cell on Randomly Moving Nanoparticles
Authors: Rotblat Barak , Yizhar Ofer , Haklai Roni , Ashery Uri , Kloog Yoel
Published: February 2006

Spatiotemporal modulation of Ras signaling from different intracellular compartments requires mechanisms allowing Ras and its signals to navigate across cells. Here, we describe one mechanism by which clusters of palmitoylated H-Ras and N-Ras isoforms but not nonpalmitoylated K-Ras diffuse through the cytoplasm, independently of ATP, on fast, randomly moving, small cytosolic nanoparticles (“rasosomes”). Rasosomes forced to diffuse out of live cells and trapped by Ras antibody beads appear as round structures of 80- to 100-nm diameter. Association of H-Ras with rasosomes requires Ras palmitoylation and the hypervariable sequence (hvr) upstream of the palmitoylated cysteines. H-Ras hvr mutants that fail to interact with rasosomes are biologically inactive. Epidermal growth factor stimulation rapidly increases active H-Ras-GTP and phosphorylated extracellular signal-regulated kinase (ERK) on rasosomes. Similarly, rasosomes carrying H-Ras(G12V) but not H-Ras are loaded with active ERK. Thus, the rasosome represents a hitherto unknown particle that enables Ras signal information to spread rapidly across cells. (Cancer Res 2006; 66(4): 1974-81)
Potent Protection against Aflatoxin-Induced Tumorigenesis through Induction of Nrf2-Regulated Pathways by the Triterpenoid 1-[2-Cyano-3-,12-Dioxooleana-1,9(11)-Dien-28-Oyl]Imidazole
Authors: Yates Melinda S. , Kwak Mi-Kyoung , Egner Patricia A. , Groopman John D. , Bodreddigari Sridevi , Sutter Thomas R. , Baumgartner Karen J. , Roebuck B.D. , Liby Karen T. , Yore Mark M. , Honda Tadashi , Gribble Gordon W. , Sporn Michael B. , Kensler Thomas W.
Published: February 2006

Synthetic triterpenoid analogues of oleanolic acid are potent inducers of the phase 2 response as well as inhibitors of inflammation. We show that the triterpenoid, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), is a highly potent chemopreventive agent that inhibits aflatoxin-induced tumorigenesis in rat liver. The chemopreventive potency of CDDO-Im was evaluated by measuring inhibition of formation of putative preneoplastic lesions (glutathione S-transferase P positive foci) in the liver of rats exposed to aflatoxin B1. CDDO-Im produces an 85% reduction in the hepatic focal burden of preneoplastic lesions at 1 μmol/kg body weight and a >99% reduction at 100 μmol/kg body weight. CDDO-Im treatment reduces levels of aflatoxin-DNA adducts by ∼40% to 90% over the range of 1 to 100 μmol/kg body weight. Additionally, changes in mRNA levels of genes involved in aflatoxin metabolism were measured in rat liver following a single dose of CDDO-Im. GSTA2, GSTA5, AFAR, and EPHX1 transcripts are elevated 6 hours following a 1 μmol/kg body weight dose of CDDO-Im. Microarray analysis using wild-type and Nrf2 knockout mice confirms that many phase 2 and antioxidant genes are induced in an Nrf2-dependent manner in mouse liver following treatment with CDDO-Im. Thus, low-micromole doses of CDDO-Im induce cytoprotective genes, inhibit DNA adduct formation, and dramatically block hepatic tumorigenesis. As a point of reference, oltipraz, an established modulator of aflatoxin metabolism in humans, is 100-fold weaker than CDDO-Im in this rat antitumorigenesis model. The unparalleled potency of CDDO-Im in vivo highlights the chemopreventive promise of targeting Nrf2 pathways with triterpenoids. (Cancer Res 2006; 66(4): 2488-94)
Enhanced Sensitivity to Cytochrome c–Induced Apoptosis Mediated by PHAPI in Breast Cancer Cells
Authors: Schafer Zachary T. , Parrish Amanda B. , Wright Kevin M. , Margolis Seth S. , Marks Jeffrey R. , Deshmukh Mohanish , Kornbluth Sally
Published: February 2006

Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c–induced apoptosome activation, further promoting chemotherapeutic resistance. We have found that breast cancer cells display an unusual sensitivity to cytochrome c–induced apoptosis when compared with their normal counterparts. This sensitivity, not observed in other cancers, resulted from enhanced recruitment of caspase-9 to the Apaf-1 caspase recruitment domain. Augmented caspase activation was mediated by PHAPI, which is overexpressed in breast cancers. Furthermore, cytochrome c microinjection into mammary epithelial cells preferentially killed malignant cells, suggesting that this phenomenon might be exploited for chemotherapeutic purposes. (Cancer Res 2006; 66(4): 2210-8)
Endothelial Progenitor Thrombospondin-1 Mediates Diabetes-Induced Delay in Reendothelialization Following Arterial Injury
Authors: Ii Masaaki , Takenaka Hideya , Asai Jun , Ibusuki Kayoko , Mizukami Yusuke , Maruyama Kazuichi , Yoon Young-sup , Wecker Andrea , Luedemann Corinne , Eaton Elizabeth , Silver Marcy , Thorne Tina , Losordo Douglas W.
Published: February 2006

Delayed reendothelialization contributes to restenosis after angioplasty and stenting in diabetes. Prior data have shown that bone marrow (BM)-derived endothelial progenitor cells (EPCs) contribute to endothelial recovery after arterial injury. We investigated the hypothesis that the EPC contribution to reendothelialization may be impaired in diabetes, resulting in delayed reendothelialization. Reendothelialization was significantly reduced in diabetic mice compared with nondiabetic mice in a wire-induced carotid denudation model. The EPC contribution to neoendothelium was significantly reduced in Tie2/LacZ BM-transplanted diabetic versus nondiabetic mice. BM from diabetic and nondiabetic mice was transplanted into nondiabetic mice, revealing that reendothelialization was impaired in the recipients of diabetic BM. To examine the relative roles of denuded artery versus EPCs in diabetes, we injected diabetic and nondiabetic EPCs intravenously after arterial injury in diabetic and nondiabetic mice. Diabetic EPCs recruitment to the neoendothelium was significantly reduced, regardless of the diabetic status of the recipient mice. In vitro, diabetic EPCs exhibited decreased migration and adhesion activities. Vascular endothelial growth factor and endothelial NO synthase expressions were also significantly reduced in diabetic EPCs. Notably, thrombospondin-1 mRNA expression was significantly upregulated in diabetic EPCs, associating with the decreased EPC adhesion activity in vitro and in vivo. Reendothelialization is impaired by malfunctioning EPCs in diabetes. Diabetic EPCs have phenotypic differences involving thrombospondin-1 expression compared with nondiabetic EPCs, revealing potential novel mechanistic insights and therapeutic targets to improve reendothelialization and reduce restenosis in diabetes.
Distinguishing Between Stroke and Mimic at the Bedside
Authors: Hand Peter J. , Kwan Joseph , Lindley Richard I. , Dennis Martin S. , Wardlaw Joanna M.
Published: February 2006

Background and Purpose—

The bedside clinical assessment of the patient with suspected stroke has not been well studied. Improving clinical skills may accelerate patient progress through the emergency department. We aimed to determine the frequency and nature of stroke mimics and to identify the key clinical features that distinguish between stroke and mimic at the bedside.

Methods—

Consecutive presentations to an urban teaching hospital with suspected stroke were recruited. A standard bedside clinical assessment was performed. The final diagnosis was determined by an expert panel, which had access to clinical features, brain imaging, and other tests. Univariate and multivariate analyses determined the bedside features that distinguished stroke from mimic.

Results—

There were 350 presentations by 336 patients. The final diagnosis was stroke in 241 of 350 (69%) and mimic in 109 (31%). The mimics included 44 events labeled “possible stroke or TIA.” Eight items independently predicted the diagnosis in patients presenting with brain attack: cognitive impairment and abnormal signs in other systems suggested a mimic, an exact time of onset, definite focal symptoms, abnormal vascular findings, presence of neurological signs, being able to lateralize the signs to the left or right side of the brain, and being able to determine a clinical stroke subclassification suggested a stroke.

Conclusions—

The bedside clinical assessment can be streamlined substantially. This has important implications for teaching less experienced clinicians how to assess the patient with suspected stroke.
Scaling Up Research in Teacher Education
Authors: Del Schalock H. , Schalock Mark D. , Ayres Robert
Published: February 2006

A recent report of the American Educational Research Association Panel on Research and Teacher Education confirms beyond question earlier findings exposing the limited utility of our research base in answering questions pertaining to policy or practice concerning preparation and licensing of teachers. Conditions accounting for this perplexing circumstance are described in detail by the panel, as are recommendations provided for overcoming them. A recent research project anticipating many of the recommendations led this article’s authors to the view that several of the recommendations need added detail to be immediately helpful to the research community and that further recommendations are needed for “scaled-up” research called for by the panel. Accordingly, suggested additions and refinements, with accompanying rationale and examples, are proposed. A central theme of this article is the need to add explanatory power to teacher education research, with the accompanying caution that doing so brings added complexity to theory, measurement, and design.
Gratitude Toward God, Stress, and Health in Late Life
Authors: Krause Neal
Published: February 2006

The purpose of this studywas to see if feeling grateful to God reduces the deleterious effects of stress on health in late life. In addition, an effort was made to test for gender differences in this process. Three main findings emerged from the analysis of data provided by a nationwide sample of older adults. First, the data suggest that olderwomen are more likely to feel grateful to God than older men. Second, the results revealed that the effects of stress (e.g., living in a deteriorated neighborhood) on health are reduced for older people who feel more grateful to God. Finally, the analyses indicated that the potentially important stress-buffering properties of gratitude toward God emerge primarily among older women but not older men.
Declining Eligibility for Social Security Spouse and Widow Benefits in the United States?
Authors: Meyer Madonna Harrington , Wolf Douglas A. , Himes Christine L.
Published: February 2006

Currently, two thirds of older women receive Social Security spouse and widow benefits, which are distributed on the basis of marital rather than employment status. But marriage rates are down, particularly among Black women. This study used June 1985, 1990, and 1995 Current Population Survey data to trace trends in marriage for women from five birth cohorts and to predict marital patterns for the latter three cohorts. The authors found that the proportion of women who will reach age 62 without 10-year marriages, and thus be ineligible for spouse and widow benefits, is increasing modestly for Whites and Hispanics but dramatically for African Americans. When women who were born in the 1960s reach age 62, 82% of Whites, 85% of Hispanics, and just 50% of Blacks will be eligible. The authors discuss alternative mechanisms for distributing benefits.
Insourcing, Not Capacity Building, a Better Model for Sustained Program Evaluation
Authors: Miller Thomas I , Kobayashi Michelle M. , Noble Paula M.
Published: February 2006

Community-based organizations (CBOs), typically small and underfunded with transient staff members, are told by funders to care for clients and verify program value. To assist CBOs with evaluations that speak to program effectiveness, many funders wish to expand the evaluation capacity of CBO staff members so that evaluation will occur as long as programs exist. In this article, the authors argue that sustainable program evaluation is unlikely when resources are devoted to training staff members to conduct evaluation in house or when money is spent for a typical external evaluation. Instead, the authors recommend a model they name “insourcing.” The insourcing model, a cross between in-house and outsourced evaluation, spreads the cost burden of the external evaluation across many CBOs while keeping evaluation in the hands of those trained in the art of evaluation. Insourcing also reduces the staff burden inevitable with internal evaluation and has the greatest potential to sustain. This article compares insourcing with other evaluation types and discusses circumstances in which insourcing could be beneficial.
Practitioner Evaluation at Work
Authors: Shaw Ian , Faulkner Alex
Published: February 2006

Practitioner involvement in evaluation, research, development, and other forms of disciplined inquiry that are small scale, local, grounded, and carried out by professionals who directly deliver those services is embraced across a wide range of professions as essential to good professional practice. However, little is known about the character, homogeneity or diversity, outcomes, motives, and practice of this activity. This article explores practitioner evaluation in social work, with an eye toward plausible connections with professional work across the public sector. The authors first explore the experience of doing practitioner evaluation, including its solitary or collaborative character, insider and outsider ascriptions and achievements, reflective moments regarding competence and capacity, and occasional glimmers of fascination with the work. The authors then explore contextualizing practitioner evaluation within its practice, agency, and professional cultures. Their third focus is through the lens of shifting practice and evaluation borderlines. The authors conclude with some provisional discussion of the implications for good practitioner evaluation.
Validation of a Fidelity Rating Instrument for Consumer-Operated Services
Authors: Mowbray Carol T. , Bybee Deborah , Holter Mark , Lewandowski Lisa
Published: February 2006

With the emphasis on the use of evidence-based practices has come a need to measure the fidelity of replications to the operations and principles of original models. Recent reviews have focused on methods to develop fidelity measures for evidence-based program models. However, the issue of how to validate such measures has been given scant attention. The research reported here attempted to validate a fidelity rating instrument (FRI) for consumer-operated drop-in centers on the basis of convergent validation methods. That is, fidelity ratings by trained observers were validated in relation to reports about similar concepts from the users of the centers. The authors describe their methods and present results indicating that all but 4 of 14 fidelity variables from the FRI were validated, as hypothesized. The authors discuss the success of this approach as well as its limitations and identify issues in the further development of fidelity measures.
The antiapoptotic gene A1/BFL1 is a WT1 target gene that mediates granulocytic differentiation and resistance to chemotherapy
Authors: Simpson Lesley A. , Burwell Emily A. , Thompson Kida A. , Shahnaz Samira , Chen Allen R. , Loeb David M.
Published: February 2006

Previous work has demonstrated that WT1 (–Ex5/–KTS) potentiates granulocyte colony-stimulating factor (G-CSF)–mediated granulocytic differentiation. This WT1 isoform suppresses cyclin E, which may contribute to the prodifferentiation effect by slowing proliferation, but WT1 target genes that affect survival might also be involved. We screened a cDNA array and identified the bCL2 family member A1/BFL1 as a new WT1 target gene in 32D cl3 murine myeloblast cells. Induction of WT1 (–Ex5/–KTS) expression is accompanied by up-regulation of A1 on the cDNA array, and this up-regulation was confirmed by semiquantitative reverse transcription–polymerase chain reaction (RT-PCR). Moreover, both promoter-reporter assays and chromatin immunoprecipitation assays suggest that this isoform of WT1 activates the promoter directly. Constitutive expression of A1 in 32D cl3 cells induces spontaneous granulocytic differentiation, with both morphologic and cell-surface antigen changes, as well as resistance both to chemotherapy and to withdrawal of interleukin-3 (IL-3). Finally, we note an association between WT1 expression and A1 expression in primary acute myeloid leukemia samples. Taken together, these results demonstrate that A1 is a new WT1 target gene involved in both granulocytic differentiation and resistance to cell death, and suggests that these genes might play an important role in the biology of high-risk leukemias.
Spectral embedding finds meaningful (relevant) structure in image and microarray data
Authors: Higgs Brandon W , Weller Jennifer , Solka Jeffrey L
Published: February 2006

Background

Accurate methods for extraction of meaningful patterns in high dimensional data have become increasingly important with the recent generation of data types containing measurements across thousands of variables. Principal components analysis (PCA) is a linear dimensionality reduction (DR) method that is unsupervised in that it relies only on the data; projections are calculated in Euclidean or a similar linear space and do not use tuning parameters for optimizing the fit to the data. However, relationships within sets of nonlinear data types, such as biological networks or images, are frequently mis-rendered into a low dimensional space by linear methods. Nonlinear methods, in contrast, attempt to model important aspects of the underlying data structure, often requiring parameter(s) fitting to the data type of interest. In many cases, the optimal parameter values vary when different classification algorithms are applied on the same rendered subspace, making the results of such methods highly dependent upon the type of classifier implemented.

Results

We present the results of applying the spectral method of Lafon, a nonlinear DR method based on the weighted graph Laplacian, that minimizes the requirements for such parameter optimization for two biological data types. We demonstrate that it is successful in determining implicit ordering of brain slice image data and in classifying separate species in microarray data, as compared to two conventional linear methods and three nonlinear methods (one of which is an alternative spectral method). This spectral implementation is shown to provide more meaningful information, by preserving important relationships, than the methods of DR presented for comparison.

Tuning parameter fitting is simple and is a general, rather than data type or experiment specific approach, for the two datasets analyzed here. Tuning parameter optimization is minimized in the DR step to each subsequent classification method, enabling the possibility of valid cross-experiment comparisons.

Conclusion

Results from the spectral method presented here exhibit the desirable properties of preserving meaningful nonlinear relationships in lower dimensional space and requiring minimal parameter fitting, providing a useful algorithm for purposes of visualization and classification across diverse datasets, a common challenge in systems biology.
Zebrafish transgenic Enhancer TRAP line database (ZETRAP)
Authors: Choo Benjamin GH , Kondrichin Igor , Parinov Sergey , Emelyanov Alexander , Go William , Toh Wei-chang , Korzh Vladimir
Published: February 2006

Background

The zebrafish,Danio rerio, is used as a model organism to study vertebrate genetics and development. An effective enhancer trap (ET) in zebrafish using theTol2transposon has been demonstrated. This approach could be used to study embryogenesis of a vertebrate species in real time and with high resolution.

Description

The information gathered during the course of systematic investigation of many ET transgenic lines have been collected and compiled in the form of an online database – the Zebrafish Enhancer TRAP lines database (ZETRAP).

Conclusion

ZETRAP is a web-based system that provides data and information to the scientific community about the developmental, genetic and genomic aspects of transgenic zebrafish lines obtained usingTol2transposon-mediated transgenesis. The current version (version 1.0) contains description of 27 ET lines that express EGFP in various organs and tissues, for example, heart, brain, notochord, gut, etc. It also includes information on insertion sites of theTol2transposon in these lines.
Phylogenetic identification of lateral genetic transfer events
Authors: Beiko Robert G , Hamilton Nicholas
Published: February 2006

Background

Lateral genetic transfer can lead to disagreements among phylogenetic trees comprising sequences from the same set of taxa. Where topological discordance is thought to have arisen through genetic transfer events, tree comparisons can be used to identify the lineages that may have shared genetic information. An 'edit path' of one or more transfer events can be represented with a series of subtree prune and regraft (SPR) operations, but finding the optimal such set of operations is NP-hard for comparisons between rooted trees, and may be so for unrooted trees as well.

Results

Efficient Evaluation of Edit Paths (EEEP) is a new tree comparison algorithm that uses evolutionarily reasonable constraints to identify and eliminate many unproductive search avenues, reducing the time required to solve many edit path problems. The performance of EEEP compares favourably to that of other algorithms when applied to strictly bifurcating trees with specified numbers of SPR operations. We also used EEEP to recover edit paths from over 19 000 unrooted, incompletely resolved protein trees containing up to 144 taxa as part of a large phylogenomic study. While inferred protein trees were far more similar to a reference supertree than random trees were to each other, the phylogenetic distance spanned by random versus inferred transfer events was similar, suggesting that real transfer events occur most frequently between closely related organisms, but can span large phylogenetic distances as well. While most of the protein trees examined here were very similar to the reference supertree, requiring zero or one edit operations for reconciliation, some trees implied up to 40 transfer events within a single orthologous set of proteins.

Conclusion

Since sequence trees typically have no implied root and may contain unresolved or multifurcating nodes, the strategy implemented in EEEP is the most appropriate for phylogenomic analyses. The high degree of consistency among inferred protein trees shows that vertical inheritance is the dominant pattern of evolution, at least for the set of organisms considered here. However, the edit paths inferred using EEEP suggest an important role for genetic transfer in the evolution of microbial genomes as well.
Tracking the evolution of alternatively spliced exons within the Dscam family
Authors: Crayton Mack E , Powell Bradford C , Vision Todd J , Giddings Morgan C
Published: February 2006

Background

The Dscam gene in the fruit fly, Drosophila melanogaster, contains twenty-four exons, four of which are composed of tandem arrays that each undergo mutually exclusive alternative splicing (4, 6, 9 and 17), potentially generating 38,016 protein isoforms. This degree of transcript diversity has not been found in mammalian homologs of Dscam. We examined the molecular evolution of exons within this gene family to locate the point of divergence for this alternative splicing pattern.

Results

Using the fruit fly Dscam exons 4, 6, 9 and 17 as seed sequences, we iteratively searched sixteen genomes for homologs, and then performed phylogenetic analyses of the resulting sequences to examine their evolutionary history. We found homologs in the nematode, arthropod and vertebrate genomes, including homologs in several vertebrates where Dscam had not been previously annotated. Among these, only the arthropods contain homologs arranged in tandem arrays indicative of mutually exclusive splicing. We found no homologs to these exons within the Arabidopsis, yeast, tunicate or sea urchin genomes but homologs to several constitutive exons from fly Dscam were present within tunicate and sea urchin. Comparing the rate of turnover within the tandem arrays of the insect taxa (fruit fly, mosquito and honeybee), we found the variants within exons 4 and 17 are well conserved in number and spatial arrangement despite 248–283 million years of divergence. In contrast, the variants within exons 6 and 9 have undergone considerable turnover since these taxa diverged, as indicated by deeply branching taxon-specific lineages.

Conclusion

Our results suggest that at least one Dscam exon array may be an ancient duplication that predates the divergence of deuterostomes from protostomes but that there is no evidence for the presence of arrays in the common ancestor of vertebrates. The different patterns of conservation and turnover among the Dscam exon arrays provide a striking example of how a gene can evolve in a modular fashion rather than as a single unit.
Compositional discordance between prokaryotic plasmids and host chromosomes
Authors: van Passel Mark WJ , Bart Aldert , Luyf Angela CM , van Kampen Antoine HC , van der Ende Arie
Published: February 2006

Background

Most plasmids depend on the host replication machinery and possess partitioning genes. These properties confine plasmids to a limited range of hosts, yielding a close and presumably stable relationship between plasmid and host. Hence, it is anticipated that due to amelioration the dinucleotide composition of plasmids is similar to that of the genome of their hosts. However, plasmids are also thought to play a major role in horizontal gene transfer and thus are frequently exchanged between hosts, suggesting dinucleotide composition dissimilarity between plasmid and host genome. We compared the dinucleotide composition of a large collection of plasmids with that of their host genomes to shed more light on this enigma.

Results

The dinucleotide frequency, coined the genome signature, facilitates the identification of putative horizontally transferred DNA in complete genome sequences, since it was found to be typical for a certain genome, and similar between related species. By comparison of the genome signature of 230 plasmid sequences with that of the genome of each respective host, we found that in general the genome signature of plasmids is dissimilar from that of their host genome.

Conclusion

Our results show that the genome signature of plasmids does not resemble that of their host genome. This indicates either absence of amelioration or a less stable relationship between plasmids and their host. We propose an indiscriminate lifestyle for plasmids preserving the genome signature discordance between these episomes and host chromosomes.
The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks
Authors: Nakahata Yasukazu , Akashi Makoto , Trcka Daniel , Yasuda Akio , Takumi Toru
Published: February 2006

Background

Circadian rhythms are endogenous, self-sustained oscillations with approximately 24-hr rhythmicity that are manifested in various physiological and metabolic processes. The circadian organization of these processes in mammals is governed by the master oscillator within the suprachiasmatic nuclei (SCN) of the hypothalamus. Recent findings revealed that circadian oscillators exist in most organs, tissues, and even in immortalized cells, and that the oscillators in peripheral tissues are likely to be coordinated by SCN, the master oscillator. Some candidates for endogenous entrainment factors have sporadically been reported, however, their details remain mainly obscure.

Results

We developed thein vitroreal-time oscillation monitoring system (IV-ROMS) by measuring the activity of luciferase coupled to the oscillatory gene promoter using photomultiplier tubes and applied this system to screen and identify factors able to influence circadian rhythmicity. Using this IV-ROMS as the primary screening of entrainment factors for circadian clocks, we identified 12 candidates as the potential entrainment factor in a total of 299 peptides and bioactive lipids. Among them, four candidates (endothelin-1, all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid) have already been reported as the entrainment factorsin vivoandin vitro. We demonstrated that one of the novel candidates, 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-γ (PPAR-γ), triggers the rhythmic expression of endogenous clock genes in NIH3T3 cells. Furthermore, we showed that 15d-PGJ2transiently inducesCry1,Cry2, andRorαmRNA expressions and that 15d-PGJ2-induced entrainment signaling pathway is PPAR-γ – and MAPKs (ERK, JNK, p38MAPK)-independent.

Conclusion

Here, we identified 15d-PGJ2as an entrainment factorin vitro. Using our developed IV-ROMS to screen 299 compounds, we found eight novel and four known molecules to be potential entrainment factors for circadian clocks, indicating that this assay system is a powerful and useful tool in initial screenings.
Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats
Authors: Iannone Michelangelo , Bulotta Stefania , Paolino Donatella , Zito Maria Cristina , Gratteri Santo , Costanzo Francesco S , Rotiroti Domenicantonio
Published: February 2006

Background

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug.

Results

We investigated the effects of low doses of MDMA in vivo using Wistar rats in the absence of acoustic stimulation (white noise; 95 Db) demonstrating that ecstasy is able to induce a significant activation (reduction of Electrocortical total power) of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to MDMA, the animals are exposed to acoustic stimulation.

Conclusion

Our data demonstrate that low doses of MDMA are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties.
Regulation of glutamatergic signalling by PACAP in the mammalian suprachiasmatic nucleus
Authors: Michel Stephan , Itri Jason , Han Jung H , Gniotczynski Kathryn , Colwell Christopher S
Published: February 2006

Background

Previous studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP). While the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors are only beginning to be understood. Speculating that PACAP may function to modulate how neurons in the suprachiasmatic nucleus respond to glutamate, we used electrophysiological and calcium imaging tools to examine possible cellular interactions between these co-transmitters.

Results

Exogenous application of PACAP increased both the amplitude and frequency of spontaneous excitatory postsynaptic currents recorded from SCN neurons in a mouse brain slice preparation. PACAP also increased the magnitude of AMPA-evoked currents through a mechanism mediated by PAC1 receptors and the adenylyl cyclase-signalling cascade. This enhancement of excitatory currents was not limited to those evoked by AMPA as the magnitude of NMDA currents were also enhanced by application of PACAP. Furthermore, PACAP enhanced AMPA and NMDA evoked calcium transients while PACAP alone produced very little change in resting calcium in most mouse SCN neurons. Finally, in rat SCN neurons, exogenous PACAP enhanced AMPA evoked currents and calcium transients as well evoked robust calcium transients on its own.

Conclusion

The results reported here show that PACAP is a potent modulator of glutamatergic signalling within the SCN in the early night.
Validation of the Ottawa Ankle Rules in Iran: A prospective survey
Authors: Yazdani Shahram , Jahandideh Hesam , Ghofrani Hossein
Published: February 2006

Background

Acute ankle injuries are one of the most common reasons for presenting to emergency departments, but only a small percentage of patients – approximately 15% – have clinically significant fractures. However, these patients are almost always referred for radiography. The Ottawa Ankle Rules (OARs) have been designed to reduce the number of unnecessary radiographs ordered for these patients. The objective of this study was to validate the OARs in the Iranian population.

Methods

This prospective survey was done among 200 patients with acute ankle injury from January 2004 to April 2004 in the Akhtar Orthopedics Hospital Emergency Department. Main outcome measures of this survey were: sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios (positive and negative) of the OARs.

Results

Sensitivity of the OARs for detecting 37 ankle fractures (23 in the malleolar zone and 14 in the midfoot zone) was 100% for each of the two zones, and 100% for both zones. Specificity of the OARs for detecting fractures was 40.50% for both zones, 40.50% for the malleolar zone, and 56.00% for the midfoot zone. Implementation of the OARs had the potential for reducing radiographs by 33%.

Conclusion

OARs are very accurate and highly sensitive tools for detecting ankle fractures. Implementation of these rules would lead to significant reduction in the number of radiographs, costs, radiation exposure and waiting times in emergency departments.
Detection of Chlamydia in the peripheral blood cells of normal donors using in vitroculture, immunofluorescence microscopy and flow cytometry techniques
Authors: Cirino Frances , Webley Wilmore C , West Corrie , Croteau Nancy L , Andrzejewski Chester , Stuart Elizabeth S
Published: February 2006

Background

Chlamydia trachomatis (Ct) and Chlamydia pneumoniae (Cp) are medically significant infectious agents associated with various chronic human pathologies. Nevertheless, specific roles in disease progression or initiation are incompletely defined. Both pathogens infect established cell lines in vitro and polymerase chain reaction (PCR) has detected Chlamydia DNA in various clinical specimens as well as in normal donor peripheral blood monocytes (PBMC). However, Chlamydia infection of other blood cell types, quantification of Chlamydia infected cells in peripheral blood and transmission of this infection in vitro have not been examined.

Methods

Cp specific titers were assessed for sera from 459 normal human donor blood (NBD) samples. Isolated white blood cells (WBC) were assayed by in vitro culture to evaluate infection transmission of blood cell borne chlamydiae. Smears of fresh blood samples (FB) were dual immunostained for microscopic identification of Chlamydia-infected cell types and aliquots also assessed using Flow Cytometry (FC).

Results

ELISA demonstrated that 219 (47.7%) of the NBD samples exhibit elevated anti-Cp antibody titers. Imunofluorescence microscopy of smears demonstrated 113 (24.6%) of samples contained intracellular Chlamydia and monoclonals to specific CD markers showed that in vivo infection of neutrophil and eosinophil/basophil cells as well as monocytes occurs. In vitro culture established WBCs of 114 (24.8%) of the NBD samples harbored infectious chlamydiae, clinically a potentially source of transmission, FC demonstrated both Chlamydia infected and uninfected cells can be readily identified and quantified.

Conclusion

NBD can harbor infected neutrophils, eosinophil/basophils and monocytes. The chlamydiae are infectious in vitro, and both total, and cell type specific Chlamydia carriage is quantifiable by FC.
Genomic screen for loci associated with tobacco usage in Mission Indians
Authors: Ehlers Cindy L , Wilhelmsen Kirk C
Published: February 2006

Background

The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California.

Methods

A structured diagnostic interview was used to define two tobacco use phenotypes: 1) any regular tobacco usage (smoked daily for one month or more) and 2) persistent tobacco usage (smoked at least 10 cigarettes a day for more than one year). Heritability was determined and a linkage analysis was performed, using genotypes for a panel 791 microsatellite polymorphisms, for the two phenotypes using variance component methods implemented in SOLAR.

Results

Analyses of multipoint variance component LOD scores for the two tobacco use phenotypes revealed two scores that exceeded 2.0 for the regular use phenotype: one on chromosomes 6 and one on 8. Four other loci on chromosomes 1,7,13, and 22 were found with LOD scores between 1.0 and 1.5. Two loci of interest were found on chromosomes 1 and 4 for the persistent use phenotype with LOD scores between 1.3–1.5. Bivariate linkage analysis was conducted at the site on chromosome 4 for persistent tobacco use and an alcohol drinking severity phenotype previously identified at this site. The maximum LOD score for the bivariate analysis for the region was 3.4, however, there was insufficient power to exclude coincident linkage.

Conclusion

While not providing evidence for linkage to specific chromosomal regions these results identify regions of interest in the genome in this Mission Indian population, for tobacco usage, some of which were identified in previous genome scans of non-native populations. Additionally, these data lend support for the hypothesis that cigarette smoking, alcohol dependence and other consumptive behaviors may share some common risk and/or protective factors in this Mission Indian population.
Uteroplacental bleeding disorders during pregnancy: do missing paternal characteristics influence risk?
Authors: Getahun Darios , Ananth Cande V , Vintzileos Anthony M
Published: February 2006

Background

Several studies have assessed the risks of uteroplacental bleeding disorders in relation to maternal characteristics. The association between uteroplacental bleeding disorders and paternal characteristics, however, has received considerably less attention. Data on paternal demographics, notably race and age, from birth certificate data are becoming increasingly incomplete in recent years. This pattern of increasingly underreporting of paternal demographic data led us to speculate that pregnancies for which paternal characteristics are partially or completely missing may be associated with increased risk for uteroplacental bleeding disorders. The objective of this study is to examine the association between placenta previa and placental abruption and missing paternal age and race.

Methods

A retrospective cohort study using U.S. linked birth/infant death data from 1995 through 2001 (n = 26,336,549) was performed. Risks of placenta previa and placental abruption among: (i) pregnancies with complete paternal age and race data; (ii) paternal age only missing; (iii) paternal race only missing; and (iv) both paternal age and race missing, were evaluated. Relative risk (RR) with 95% confidence interval (CI) for placenta previa and placental abruption by missing paternal characteristics were derived after adjusting for confounders.

Results

Adjusted RR for placental abruption were 1.30 (95% CI 1.24, 1.37), 1.00 (95% CI 0.95, 1.05), and 1.08 (95% CI 1.06, 1.10) among pregnancies with "paternal age only", "paternal race only", and "both paternal age and race" missing, respectively. The increased risk of placental abruption among the "paternal age only missing" category is partly explained by increased risks among whites aged 20–29 years, and among blacks aged ≥30 years. However, no clear patterns in the associations between missing paternal characteristics and placenta previa were evident.

Conclusion

Missing paternal characteristics are associated with increased risk of placental abruption, likely mediated through low socio-economic conditions.
What is the optimal gestational age for twin delivery
Authors: Bakr Ahmad F , Karkour Tarek
Published: February 2006

Background

The question about outcome in twins delivered early versus late remains unanswered. The objective of this study was to evaluate the association of the timing of delivering twins and the perinatal outcome.

Methods

A prospective cohort study was carried-out in Alexandria University Maternity Hospital. We planned to examine the records of twin deliveries over 2 years. The inclusion criteria were twin deliveries with gestational age at delivery at least 36 completed weeks. Twins of mothers with chronic illness and those with congenital anomalies were excluded. Perinatal outcome parameters (morbidity and mortality) were defined and evaluated.

Results

Out of 273 twin sets, 197 (72.2%) met the inclusion criteria. They were classified into 3 groups according to the gestational age at delivery. Neonatal morbidity and maternal complications were higher in those delivered earlier. Twins electively delivered had worse outcome than those delivered spontaneously. In the elective group, there was no difference in the outcome between those delivered earlier or later.

Conclusion

Twins, when the pregnancy is uncomplicated, continue to grow and mature with advancement of the gestational age. In the absence of significant maternal complications, it is advisable to deliver twins only at 38 completed weeks' gestation or later to avoid neonatal complications.
Severe respiratory distress in term infants born electively at high altitude
Authors: Bakr Ahmad F , Abbas Mohammad M
Published: February 2006

Background

We studied the contribution of elective delivery to severe respiratory distress syndrome (RDS) in term babies born at high altitude.

Methods

We prospectively studied the charts of term babies born in Taif Maternity Hospital (1640 m above sea level) between 1/1/2004 and 31/10/2004 who developed RDS and required mechanical ventilation.

Results

8634 deliveries occurred from 37–<41 weeks; 13 (0.15%) had RDS requiring mechanical ventilation. Seven infants delivered at 37–<38 weeks, (OR for RDS = 26 95%CI -4.6 to 5.8), five delivered at 38–<39 weeks, (OR for RDS = 10 95%CI -4.9 to 5.4) and one delivered at >39 weeks. Six of 13 infants were electively delivered without documented lung maturity.

Conclusion

Infants born at 37 and 38 weeks' gestation remain at significantly increased risk for severe RDS. Elective delivery is responsible for 50% of the potentially avoidable cases. Our data suggest that the altitude does not seem to influence the incidence of severe RDS in term infants born electively.
Total plasma homocysteine, folate, and vitamin b12 status in healthy Iranian adults: the Tehran homocysteine survey (2003–2004)/a cross – sectional population based study
Authors: Fakhrzadeh Hossein , Ghotbi Sara , Pourebrahim Rasoul , Nouri Masoumeh , Heshmat Ramin , Bandarian Fatemeh , Shafaee Alireza , Larijani Bagher
Published: February 2006

Background

Elevated plasma total homocysteine is an independent risk factor for cardiovascular disease and a sensitive marker of the inadequate vitamin B12 and folate insufficiency. Folate and vitamin B12 have a protective effect on cardiovascular disease. This population based study was conducted to evaluate the plasma total homocysteine, folate, and vitamin B12 in healthy Iranian individuals.

Methods

This study was a part of the Cardiovascular Risk Factors Survey in the Population Lab Region of Tehran University has been designed and conducted based on the methodology of MONICA/WHO Project. A total of 1214 people aged 25–64 years, were recruited and assessed regarding demographic characteristics, homocysteine, folate, and vitamin B12 levels with interview, questionnaires, examination and blood sampling. Blood samples were gathered and analyzed according to standard methods.

Results

The variables were assessed in 1214 participants including 428 men (35.3%) and 786 women (64.7%). Age-adjusted prevalence of hyperhomocysteinemia (Hcy≥15 μmol/L) was 73.1% in men and 41.07% in women (P < 0.0001). Geometric mean of plasma homocysteine was 19.02 ± 1.46 μmol/l in men and 14.05 ± 1.45 μmol/l in women (P < 0.004) which increased by ageing. Age-adjusted prevalence of low serum folate level was 98.67% in men and 97.92% in women. Age-adjusted prevalence of low serum vitamin B12 level was 26.32% in men and 27.2% in women. Correlation coefficients (Pearson's r) between log tHcy and serum folate, and vitamin B12 indicated an inverse correlation (r = -0.27, r = -0.19, P < 0.0001, respectively).

Conclusion

These results revealed that the prevalence of hyperhomocysteinemia, low folate and vitamin B12 levels are considerably higher than other communities. Implementation of preventive interventions such as food fortification with folic acid is necessary.
Clinical categories of patients and encounter rates in primary health care – a three-year study in defined populations
Authors: Carlsson Lennart , Strender Lars-Erik , Fridh Gerd , Nilsson Gunnar H
Published: February 2006

Background

The objective was to estimate the proportion of inhabitants with a diagnosis-registered encounter with a general practitioner, and to elucidate annual variations of clinical categories of patients in terms of their individual comorbidity.

Methods

A three-year retrospective study of encounter data from electronic patient records, with an annual-based application of the Johns Hopkins Adjusted Clinical Groups (ACG) system. Data were retrieved from every patient with a diagnosis-registered encounter with a GP during the period 2001–2003 at 13 publicly managed primary health care centres in Blekinge county, southeastern Sweden, with about 150000 inhabitants. Main outcome measures: Proportions of inhabitants with a diagnosis-registered encounter, and ranges of the annual proportions of categories of patients according to ACGs.

Results

The proportion of inhabitants with a diagnosis-registered encounter ranged from about 64.0% to 90.6% for the primary health care centres, and averaged about 76.5% for all inhabitants. In a three-year perspective the average range of categories of patients was about 0.4% on the county level, and about 0.9% on the primary health care centre level. About one third of the patients each year had a constellation of two or more types of morbidity.

Conclusion

About three fourths of all inhabitants had one or more diagnosis-registered encounters with a general practitioner during the three-year period. The annual variation of categories of patients according to ACGs was small on both the county and the primary health care centre level. The ACG system seems useful for demonstrating and predicting various aspects of clinical categories of patients in Swedish primary health care.