bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Phenylethyl Isothiocyanate on Early Molecular Events in N-Nitrosomethylbenzylamine–Induced Cytotoxicity in Rat Esophagus
Authors: Reen Rashmeet K. , Dombkowski Alan A. , Kresty Laura A. , Cukovic Daniela , Mele Jennifer M. , Salagrama Sridevi , Nines Ronald , Stoner Gary D.
Published: July 2007

There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)–induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were fed AIN-76A diet or AIN-76A diet containing PEITC for 3 weeks. During the 3rd week of dietary treatment, they were administered three s.c. doses of NMBA (0.5 mg/kg body weight). Rats were sacrificed 24 h after the last treatment; esophagi were excised and processed for histologic grading, microarray and real-time PCR analysis. Histopathologic analysis showed that treatment of rats with PEITC had a protective effect on NMBA-induced preneoplastic lesions in the rat esophagus. We identified 2,261 genes that were differentially expressed in the NMBA-treated versus control esophagi and 1,936 genes in the PEITC + NMBA versus NMBA-treated esophagi. The intersection of these two sets resulted in the identification of 1,323 genes in NMBA-treated esophagus, the vast majority of which were modulated by PEITC to near-normal levels of expression. Measured changes in the expression levels of eight selected genes were validated using real-time PCR. Results from 12 microarrays indicated that PEITC treatment had a genome-wide modulating effect on NMBA-induced gene expression. Samples obtained from animals treated with PEITC alone or cotreated with PEITC + NMBA were more similar to controls than to samples treated with NMBA alone. [Cancer Res 2007;67(13):1–9]
The Inhibitory Effect of (−)-Epigallocatechin Gallate on Activation of the Epidermal Growth Factor Receptor Is Associated with Altered Lipid Order in HT29 Colon Cancer Cells
Authors: Adachi Seiji , Nagao Tomokazu , Ingolfsson Helgi I. , Maxfield Frederick R. , Andersen Olaf S. , Kopelovich Levy , Weinstein I. Bernard
Published: July 2007

(−)-Epigallocatechin gallate (EGCG), a major biologically active constituent of green tea, inhibits activation of the epidermal growth factor (EGF) receptor (EGFR) and downstream signaling pathways in several types of human cancer cells, but the precise mechanism is not known. Because several plasma membrane-associated receptor tyrosine kinases (RTK) including EGFR are localized in detergent-insoluble ordered membrane domains, so-called “lipid rafts,” we examined whether the inhibitory effect of EGCG on activation of the EGFR is associated with changes in membrane lipid order in HT29 colon cancer cells. First, we did cold Triton X-100 solubility assays. Phosphorylated (activated) EGFR was found only in the Triton X-100–insoluble (lipid raft) fraction, whereas total cellular EGFR was present in the Triton X-100–soluble fraction. Pretreatment with EGCG inhibited the binding of Alexa Fluor 488–labeled EGF to the cells and also inhibited EGF-induced dimerization of the EGFR. To examine possible effects of EGCG on membrane lipid organization, we labeled the cells with the fluorescent lipid analogue 1, 1′-dihexadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate, which preferentially incorporates into ordered membrane domains in cells and found that subsequent treatment with EGCG caused a marked reduction in the Triton X-100–resistant membrane fraction. Polyphenon E, a mixture of green tea catechins, had a similar effect but (−)-epicatechin (EC), the biologically inactive compound, did not significantly alter the Triton X-100 solubility properties of the membrane. Furthermore, we found that EGCG but not EC caused dramatic changes in the function of bilayer-incorporated gramicidin channels. Taken together, these findings suggest that EGCG inhibits the binding of EGF to the EGFR and the subsequent dimerization and activation of the EGFR by altering membrane organization. These effects may also explain the ability of EGCG to inhibit activation of other membrane-associated RTKs, and they may play a critical role in the anticancer effects of this and related compounds. [Cancer Res 2007;67(13):6493–501]
A Novel Epidermal Growth Factor Receptor Inhibitor Promotes Apoptosis in Non–Small Cell Lung Cancer Cells Resistant to Erlotinib
Authors: de La Motte Rouge Thibault , Galluzzi Lorenzo , Olaussen Ken A. , Zermati Yael , Tasdemir Ezgi , Robert Thomas , Ripoche Hugues , Lazar Vladimir , Dessen Philippe , Harper Francis , Pierron Gerard , Pinna Guillaume , Araujo Natalia , Harel-Belan Annick , Armand Jean-Pierre , Wong Tai Wai , Soria Jean Charles , Kroemer Guido
Published: July 2007

Non–small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) responds to EGFR tyrosine kinase inhibitors such as erlotinib. However, secondary somatic EGFR mutations (e.g., T790M) confer resistance to erlotinib. BMS-690514, a novel panHER/vascular endothelial growth factor receptor (VEGFR) inhibitor described here, exerted antiproliferative and proapoptotic effects on NSCLC cell lines, with prominent efficacy on H1975 cells expressing the T790M mutation. In this model, BMS-690514 induced a G1 cell cycle arrest, as well as ultrastructural hallmarks of apoptosis, mitochondrial release of cytochrome c, and activation of caspases involved in the intrinsic (e.g., caspase-2, caspase-3, caspase-7, and caspase-9), but not in the extrinsic (e.g., caspase-8), pathway. Caspase inhibition conferred partial protection against BMS-690514 cytotoxicity, pointing to the involvement of both caspase-dependent and caspase-independent effector mechanisms. Transcriptome analyses revealed the up-regulation of proapoptotic (e.g., Bim, Puma) and cell cycle inhibitory (e.g., p27Kip1, p57Kip2) factors, as well as the down-regulation of antiapoptotic (e.g., Mcl1), heat shock (e.g., HSP40, HSP70, HSP90), and cell cycle promoting [e.g., cyclins B1, D1, and D3; cyclin-dependent kinase 1 (CDK1); MCM family proteins; proliferating cell nuclear antigen (PCNA)] proteins. BMS-690514–induced death of H1975 cells was modified in a unique fashion by a panel of small interfering RNAs targeting apoptosis modulators. Down-regulation of components of the nuclear factor-κB survival pathway (e.g., p65, Nemo/IKKγ, TAB2) sensitized cells to BMS-690514, whereas knockdown of proapoptotic factors (e.g., Puma, Bax, Bak, caspase-2, etc.) and DNA damage–related proteins (e.g., ERCC1, hTERT) exerted cytoprotective effects. BMS-690514 is a new pan-HER/VEGFR inhibitor that may become an alternative to erlotinib for the treatment of NSCLC. [Cancer Res 2007;67(13):6253–62]
The Unhydrolyzable Fenretinide Analogue 4-Hydroxybenzylretinone Induces the Proapoptotic Genes GADD153 (CHOP) and Bcl-2–Binding Component 3 (PUMA) and Apoptosis that Is Caspase- Dependent and Independent of the Retinoic Acid Receptor
Authors: Anding Allyson L. , Chapman Jason S. , Barnett Derek W. , Curley Robert W. , Clagett-Dame Margaret
Published: July 2007

The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) induces apoptosis in a variety of cell lines and has shown promise as an anticancer agent both in vitro and in vivo. The clinical dose of 4-HPR, however, is limited by residual-associated toxicities, indicating a need for a less toxic drug. In this study, we show that 4-hydroxybenzylretinone (4-HBR), the unhydrolyzable analogue of 4-HPR, is effective in producing apoptosis in a variety of 4-HPR–sensitive cell lines, including breast cancer, neuroblastoma, and leukemia cells. We also show through the use of a pan-caspase inhibitor that this 4-HBR–induced apoptosis is dependent, at least in part, on caspase activity. 4-HBR is shown to exhibit binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death and induces expression of all-trans-retinoic acid–responsive genes that can be blocked by a RAR pan-antagonist. However, through the use of this RAR pan-antagonist, 4-HBR–induced apoptosis and cell death is shown to be independent of the RAR signaling pathway. To further characterize the mechanism of action of 4-HBR, expression of the endoplasmic reticulum stress–induced genes GADD153 and Bcl-2–binding component 3 was examined. These mRNAs are shown to be rapidly induced in 4-HBR–treated and 4-HPR–treated breast cancer cells, and this up-regulation is also shown to be independent of the RARs. These results suggest that a stress-mediated apoptotic cascade is involved in the mechanism of action of these retinoids. [Cancer Res 2007;67(13):6270–7]
Serum Heart-Type Fatty Acid-Binding Protein and Cerebrospinal Fluid Tau: Marker Candidates for Dementia with Lewy Bodies
Authors: Mollenhauer Brit , Steinacker Petra , Bahn Erik , Bibl Mirko , Brechlin Peter , Schlossmacher Michael G. , Locascio Joseph J. , Wiltfang Jens , Kretzschmar Hans A. , Poser Sigrid , Trenkwalder Claudia , Otto Markus
Published: July 2007

Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nondemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of H-FABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum H-FABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio ≧8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB.
Effects of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate, on thrombus formation and bleeding time in rats
Authors: Stassen Jean-Marie , Priepke Henning , Ries Uwe Joerg , Hauel Norbert , Wienen Wolfgang
Published: July 2007

Dabigatran is a reversible direct, selective thrombin inhibitor, undergoing clinical development as its orally active prodrug, dabigatran etexilate. The objective of this trial was to assess the antithrombotic and anticoagulant effects of dabigatran and dabigatran etexilate in a rat model of venous thrombosis. In order to do this a modifiedWessler model was used to assess the antithrombotic and anticoagulant effects of intravenous (i.v.) dabigatran and oral dabigatran etexilate administration. In addition, a rat tail bleeding time model was used to investigate the antihemostatic effect of dabigatran.The study demonstrated that bolus administration of dabigatran (0.01–0.1 mg/kg) reduced thrombus formation dose-dependently,with an ED50 (50% of the effective dose) of 0.033 mg/kg and complete inhibition at 0.1 mg/kg. By comparison,ED50 values for heparin (0.03–0.3 mg/kg),hirudin (0.01–0.5 mg/kg) and melagatran (0.1–0.5 mg/kg) were 0.07, 0.15 and 0.12 mg/kg, respectively. Oral administration of dabigatran etexilate (5–30 mg/kg) inhibited thrombus formation in a dose- and time-dependent manner, with maximum inhibition within 30 min of pretreatment, suggesting a rapid onset of action. Following i.v. administration of dabigatran (0.1–1.0 mg/kg), a statistically significant prolongation of bleeding time was observed at doses at least 15- and 5-fold greater than ED50 and ED100 (100% of the effective dose) doses, respectively; there was no significant increase in bleeding tendency at the maximum therapeutically effective dose (0.1 mg/kg). It can be concluded that dabigatran and its oral prodrug, dabigatran etexilate, show promise in the management of thromboembolic disease.
Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man?
Authors: Braun Thomas , Borchardt Thilo
Published: July 2007

The mammalian heart cannot regenerate substantial cardiac injuries, while certain non-mammalian vertebrates such as certain fish (Danio rerio) and amphibiae (Notophthalmus viridescens) are able to repair the heart without functional impairment. In mammalians, the prevailing repair process is accompanied by fibrosis and scarring, while zebrafish and newts can replace lost contractile tissue by newly formed cardiac muscle with only little or no scar formation.A better understanding of cardiac regeneration in non-mammalian vertebrates might provide new insights for the manipulation of regenerative pathways in the human heart. Here, we summarize the current knowledge in cardiac regeneration of newts and the principal differences to repair processes in mammalian hearts.
Microfluidic reveals generation of platelet-strings on tumoractivated endothelium
Authors: Kleinerüschkamp Felix , Barg Alexej , Schnaeker Eva-Maria , Huck Volker , Schneider Matthias , Steinhoff Martin , Goerge Tobias , Schneider Stefan
Published: July 2007

Neoplastic diseases are often associated with thromboembolic events,however the precise mechanism underlying this observation is a matter of ongoing investigation. It is known that matrixmetalloproteinase- 1 (MMP-1) canonically activates the thrombin receptor (PAR-1) and we recently reported that highly metastatic tumor cells of melanoma and colon cancer are secreting matrixmetalloproteinase-1. This tumor-derived MMP1 was shown to be a major activator of endothelial PAR-1, thus leading to endothelial cell activation. As tumor-induced thrombosis is a characteristic of metastazing tumors, we investigated whether tumor-derived supernatant (TUSN) from melanoma and colon cancer may induce adhesion of circulating platelets,an initial step in thrombus formation.A time-course study revealed that TU-SN induces a rapid secretion of von Willebrand factor (VWF) within minutes. Using a novel microfluidic device we analyzed platelet-endothelial interactions in a closed circuit. Immunofluorescence imaging showed that TU-SN rapidly induces platelet- string formation via secreted VWF. We demonstrated that tumor-derived supernatant is a potent agonist inducing platelet adhesion under flow conditions.
VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients
Authors: Vroling Laura , Yuana Yuana , Schuurhuis Gerrit Jan , van Hinsbergh Victor , Gundy Chad , de Haas Richard , van Cruijsen Hester , Boven Epie , Hoekman Klaas , Broxterman Henk
Published: July 2007

Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumorbearing mice have pointed to the potential importance of VEGFresponding circulating (endothelial) progenitor cells in tumor growth.We have studied circulating CD31- and/or CD34-positive cell populations with a low to moderateVEGFR2 expression in human volunteers and cancer patients. We recognized four cell populations, which were further characterized by their content of major hematopoetic progenitor, monocytic, endothelial and platelet markers. After establishing the test-retest stability of the measurements in nine patients, we determined the frequencies of the various cell populations in a group of 20 volunteers and 14 cancer patients.Two populations were markedly increased in cancer patients. Small CD45neg /CD34bright/VEGFR2+ cells amounted to 12 and 64 cells/ml (P<0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45bright (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P=0.017). A third population of CD45dim/CD34bright/ VEGFR2low cells amounted to 25 and 30 cells/ml (P=0.38).Unexpectedly, a population of mainly anucleated CD45low/CD31bright/ CD41bright cells was present in numbers of 9,076 and 16,697/ml (P=0.04) in volunteers and cancer patients, which contained a VEGFR2low (compared to IgG isotype control) expressing population amounting to 1,142 and 1,642 cells/ml (P=0.12). This fourth population probably reflects large platelets. The role of the herein identified VEGFR2+ circulating cell populations deserve further investigation in cancer patients treated with VEGF(R)-targeted therapies. Quantification of such cell populations in the blood of tumor patients may be valuable to monitor the efficacy of anti-angiogenic treatment.
Wild-Type ApoA-I and the Milano Variant Have Similar Abilities to Stimulate Cellular Lipid Mobilization and Efflux
Authors: Weibel Ginny L. , Alexander Eric T. , Joshi Michelle R. , Rader Daniel J. , Lund-Katz Sissel , Phillips Michael C. , Rothblat George H.
Published: July 2007

Objective—

The present study is a comparative investigation of cellular lipid mobilization and efflux to lipid-free human apoA-I and apoA-I
Milano
, reconstituted high-density lipoprotein (rHDL) particles containing these proteins and serum isolated from mice expressing human apoA-I or apoA-I
Milano
.

Methods and Results—

Cholesterol and phospholipid efflux to these acceptors was measured in cell systems designed to assess the contributions of ATP-binding cassette A1 (ABCA1), scavenger receptor type BI (SRBI), and cellular lipid content to cholesterol and phospholipid efflux. Acceptors containing the Milano variant of apoA-I showed no functional increase in lipid efflux in all assays when compared with wild-type apoA-I. In fact, in some systems, acceptors containing the Milano variant of apoA-I promoted significantly less efflux than the acceptors containing wild-type apoA-I (apoA-I
wt
). Additionally, intracellular cholesteryl ester hydrolysis in macrophage foam cells was not different in the presence of either apoA-I
Milano
or apoA-I
wt
.

Conclusion—

Collectively these studies suggest that if the Milano variant of apoA-I offers greater atheroprotection than wild-type apoA-I, it is not attributable to greater cellular lipid mobilization.
Comparison of Clinical Characteristics and Functional Outcomes of Ischemic Stroke in Different Vascular Territories
Authors: Ng Yee Sien , Stein Joel , Ning MingMing , Black-Schaffer Randie M.
Published: July 2007

Background and Purpose—

We aim to compare demographics and functional outcomes of patients with stroke in a variety of vascular territories who underwent inpatient rehabilitation. Such comparative data are important in functional prognostication, rehabilitation, and healthcare planning, but literature is scarce and isolated.

Methods—

Using data collected prospectively over a 9-year period, we studied 2213 individuals who sustained first-ever ischemic strokes and were admitted to an inpatient stroke rehabilitation program. Strokes were divided into anterior cerebral artery, middle cerebral artery (MCA), posterior cerebral artery, brain stem, cerebellar, small-vessel strokes, and strokes occurring in more than one vascular territory. The main functional outcome measure was the Functional Independence Measure (FIM). Repeated-measures analysis of covariance with post hoc analyses was used to compare functional outcomes of the stroke groups.

Results—

The most common stroke groups were MCA stroke (50.8%) and small-vessel stroke (12.8%). After adjustments for age, gender, risk factors, and admission year, the stroke groups can be arranged from most to least severe disability on admission: strokes in more than one vascular territory, MCA, anterior cerebral artery, posterior cerebral artery, brain stem, cerebellar, and small-vessel strokes. The sequence was similar on discharge, except cerebellar strokes had the least disability rather than small-vessel strokes. Hemispheric (more than one vascular territory, MCA, anterior cerebral artery, posterior cerebral artery) strokes collectively have significantly lower admission and discharge total and cognitive FIM scores compared with the other stroke groups. MCA stroke had the lowest FIM efficiency and cerebellar stroke the highest. Regardless, patients with stroke made significant (
P
<0.001) and approximately equal (
P
=0.535) functional gains in all groups. Higher admission motor and cognitive FIM scores, longer rehabilitation stay, younger patients, lower number of medical complications, and a year of admission after 2000 were associated with higher discharge total FIM scores on multiple regression analysis.

Conclusions—

Patients with stroke made significant functional gains and should be offered rehabilitation regardless of stroke vascular territory. The initial functional status at admission, rather than the stroke subgroup, better predicts discharge functional outcomes postrehabilitation.
Managing the machine in the stacks: operations research, bibliographic control and library computerization, 1950–2000
Authors: Rau Erik P.
Published: July 2007

Traces efforts to employ operations research (OR) in managing technological innovation in the library. Briefly discusses the World War II origins of OR and focuses on its post-war application to libraries and their efforts to improve systems of bibliographic control in the wake of the deluge of documents generated by scientific and technological advance and by the onset of the Cold War. Examines three pioneering attempts to apply OR to research libraries — by Philip Morse at MIT, Michael Buckland at the University of Lancaster, England, and by Ferdinand Leimkuhler at Purdue University. Culminates by exploring OR's legacy in the computerized research library and possible reasons for its sudden disappearance.
CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25− T cells
Authors: Yang Zhi-Zhang , Novak Anne J. , Ziesmer Steven C. , Witzig Thomas E. , Ansell Stephen M.
Published: July 2007

Foxp3 expression was initially thought to be restricted to the CD4+CD25+ regulatory T-cell population. However, recent studies suggest that forkhead box P3 (Foxp3) is expressed in CD4+CD25− T cells in aged mice. In the present study in B-cell non-Hodgkin lymphoma (NHL), we found that a subset of intratumoral but not peripheral blood CD4+CD25− T cells, comprising about 15% of intratumoral CD4+ T cells, express Foxp3 and are capable of suppressing the proliferation of autologous infiltrating CD8+ T cells. In vitro activation with OKT3/anti-CD28 antibody (Ab) or dendritic cells (DCs) induced Foxp3 expression in a subset of these CD4+CD25−Foxp3− T cells. We found that the presence of lymphoma B cells during activation augmented activation-induced Foxp3 expression in CD4+CD25− T cells. We also found that CD70+ lymphoma B cells significantly contributed to the activation-induced Foxp3 expression in intratumoral CD4+CD25− T cells. Furthermore, the blockade of CD27-CD70 interaction by anti-CD70 Ab abrogated lymphoma B-cell–mediated induction of Foxp3 expression in intratumoral CD4+CD25− T cells. Taken together, these studies reveal a novel role for NHL B cells in the development of intratumoral regulatory T cells.
echinus, required for interommatidial cell sorting and cell death in the Drosophila pupal retina, encodes a protein with homology to ubiquitin-specific proteases
Authors: Copeland Jeffrey M , Bosdet Ian , Freeman J Douglas , Guo Ming , Gorski Sharon M , Hay Bruce A
Published: July 2007

Background

Programmed cell death is used to remove excess cells between ommatidia in theDrosophilapupal retina. This death is required to establish the crystalline, hexagonal packing of ommatidia that characterizes the adult fly eye. In previously describedechinusmutants, interommatidial cell sorting, which precedes cell death, occurred relatively normally. Interommatidial cell death was partially suppressed, resulting in adult eyes that contained excess pigment cells, and in which ommatidia were mildly disordered. These results have suggested thatechinusfunctions in the pupal retina primarily to promote interommatidial cell death.

Results

We generated a number of newechinus alleles, some likely null mutants. Analysis of these alleles provides evidence thatechinushas roles in cell sorting as well as cell death.echinusencodes a protein with homology to ubiquitin-specific proteases. These proteins cleave ubiquitin-conjugated proteins at the ubiquitin C-terminus. Theechinuslocus encodes multiple splice forms, including two proteins that lack residues thought to be critical for deubiquitination activity. Surprisingly, ubiquitous expression in the eye of versions of Echinus that lack residues critical for ubiquitin specific protease activity, as well as a version predicted to be functional, rescue theechinusloss-of-function phenotype. Finally, genetic interactions were not detected betweenechinusloss and gain-of-function and a number of known apoptotic regulators. These include Notch, EGFR, the caspases Dronc, Drice, Dcp-1, Dream, the caspase activators, Rpr, Hid, and Grim, the caspase inhibitor DIAP1, and Lozenge or Klumpfuss.

Conclusion

Theechinuslocus encodes multiple splice forms of a protein with homology to ubiquitin-specific proteases, but protease activity is unlikely to be required forechinusfunction, at least whenechinusis overexpressed. Characterization of likelyechinusnull alleles and genetic interactions suggests thatechinusacts at a novel point(s) to regulate interommatidial cell sorting and/or cell death in the fly eye.
Support to woman by a companion of her choice during childbirth: a randomized controlled trial
Authors: Bruggemann Odalea M , Parpinelli Mary A , Osis Maria JD , Cecatti Jose G , Neto Antonio S Carvalhinho
Published: July 2007

Background

To evaluate the effectiveness and safety of the support given to women by a companion of their choice during labor and delivery.

Methods

A total of 212 primiparous women were enrolled in a randomized controlled clinical trial carried out between February 2004 and March 2005. One hundred and five women were allocated to the group in which support was permitted and 107 to the group in which there was no support. Variables regarding patient satisfaction and events related to obstetrical care, neonatal results and breastfeeding were evaluated. Student's t-test or Wilcoxon's test, chi-square or Fisher's exact test, risk ratios, and their respective 95% confidence intervals were used in the statistical analysis.

Results

Overall, the women in the support group were more satisfied with labor (median 88.0 versus 76.0, p < 0.0001) and delivery (median 91.4 versus 77.1, p < 0.0001). During labor, patient satisfaction was associated with the presence of a companion (RR 8.06; 95%CI: 4.84 – 13.43), with care received (RR 1.11; 95%CI: 1.01 – 1.22) and with medical guidance (RR 1.14 95%CI: 1.01 – 1.28). During delivery, satisfaction was associated with having a companion (RR 5.57, 95%CI: 3.70 – 8.38), with care received (RR 1.11 95%CI: 1.01 – 1.22) and with vaginal delivery (RR 1.33 95%CI:1.02 – 1.74). The only factor that was significantly lower in the support group was the occurrence of meconium-stained amniotic fluid (RR 0.51; 95%CI: 0.28 – 0.94). There was no statistically significant difference between the two groups with respect to any of the other variables.

Conclusion

The presence of a companion of the woman's choice had a positive influence on her satisfaction with the birth process and did not interfere with other events and interventions, with neonatal outcome or breastfeeding.
Strategy for encoding and comparison of gene expression signatures
Authors: Yi Yajun , Li Chun , Miller Clay , George Alfred L
Published: July 2007

EXALT (EXpression signature AnaLysis Tool) is a computational system enabling comparisons of microarray data across experimental platforms and different laboratories http://seq.mc.vanderbilt.edu/exalt/. An essential feature of EXALT is a database holding thousands of gene expression signatures extracted from the Gene Expression Omnibus, and encoded in a searchable format. This novel approach to performing global comparisons of shared microarray data may have enormous value when coupled directly with a shared data repository.
Comprehensive characterization of the cis-regulatory code responsible for the spatio-temporal expression of olSix3.2in the developing medaka forebrain
Authors: Conte Ivan , Bovolenta Paola
Published: July 2007

Background

Embryonic development is coordinated by sets of cis-regulatory elements that are collectively responsible for the precise spatio-temporal organization of regulatory gene networks. There is little information on how these elements, which are often associated with highly conserved noncoding sequences, are combined to generate precise gene expression patterns in vertebrates. To address this issue, we have focused on Six3, an important regulator of vertebrate forebrain development.

Results

Using computational analysis and exploiting the diversity of teleost genomes, we identified a cluster of highly conserved noncoding sequences surrounding the Six3 gene. Transgenesis in medaka fish demonstrates that these sequences have enhancer, silencer, and silencer blocker activities that are differentially combined to control the entire distribution of Six3.

Conclusion

This report provides the first example of the precise regulatory code necessary for the expression of a vertebrate gene, and offers a unique framework for defining the interplay of trans-acting factors that control the evolutionary conserved use of Six3.
Stop-go temperature logging for precision applications
Authors: Harris Robert N. , Chapman David S.
Published: July 2007

We describe a new field procedure for stop-go temperature logging of boreholes that attains millikelvin precision. Temperature is recorded continuously throughout the entire log, but the logging probe is held stationary for a fixed time at discrete depth intervals. Equilibrium temperatures at the discrete depths are based on extrapolations of time series using the heat-diffusion theory for an infinitely long cylinder. For a Fenwahl K212E thermistor probe having a time constant of about [Formula: see text], temperatures are still [Formula: see text] away from equilibrium after a wait time of [Formula: see text]; but temperatures extrapolated from the time series are within [Formula: see text] of equilibrium. A time series over a duration of seven time constants of the probe allows the user to reproduce temperature estimates within millikelvins. The technique was applied at GC-1, a borehole in northwestern Utah.
Adjuvant Chemotherapy for Early-Stage Ovarian Cancer: Review of the Literature
Authors: Tropé Claes , Kaern Janne
Published: July 2007

Purpose

This overview summarizes studies with acceptable quality and validity and presents a synthesis of the effectiveness on adjuvant therapy after surgery for early ovarian cancer (EOC) patients.

Methods

The literature published between 1970 and 2006 was identified systematically by computer-based searches in MEDLINE and Cochrane library.

Results

Twenty-two prospective randomized studies were analyzed, which included 4,626 patients. No difference between adjuvant chemotherapy (AC) and radiotherapy was found. There is agreement on that patients with stage IA, grade 1 tumors have excellent survival and do not need postsurgical therapy. The International Collaborative Ovarian Neoplasm 1/Adjuvant Chemotherapy in Ovarian Neoplasm trials were the first to show an effect on survival of AC, but in patients with adequate surgical staging, there was no additional effect of AC. For patients who are staged incompletely at the time of initial surgery, completion of the staging procedure with either laparoscopy or laparotomy is a reasonable approach before a final decision is made regarding the need for AC. If full staging cannot be performed due to medical contraindication or patient refusal, consideration of AC is reasonable in selected patients. Using prognostic variables such as grade, International Federation of Gynecology and Obstetrics substage, pretreatment of CA-125 ≤ 30 U/mL, and DNA ploidy, it is possible to divide patients into risk groups to avoid overtreatment. Gynecologic Oncology Group study 157 suggests that it may be possible to minimize chemotherapy-induced toxicity by using three instead of six cycles of AC, although it is not known fully whether this will compromise effectiveness.

Conclusion

Future randomized studies in EOC will include the investigation of new targeted therapies and new prognostic factors in adequately staged patients.
Novel Approaches in Advancing the Treatment of Epithelial Ovarian Cancer: The Role of Angiogenesis Inhibition
Authors: Martin Lainie , Schilder Russell
Published: July 2007

Despite an aggressive approach of surgical cytoreduction and adjuvant combination chemotherapy, ovarian cancer mortality remains a significant problem. We are entering a new era of cancer therapeutics in which targeted therapies offer the potential for improvement in long-term disease control with fewer toxicities. The greatest success of targeted therapy to date in the setting of epithelial ovarian carcinoma has come from angiogenesis inhibition. This review will focus on the role of angiogenesis in normal ovarian function as well as in ovarian carcinoma development and disease progression. Current knowledge about the molecular pathways involved in angiogenesis and various approaches to angiogenesis inhibition in the treatment of ovarian cancer are discussed. Current data regarding the role of bevacizumab and other novel agents in the treatment of ovarian carcinoma are summarized.
Species with fuzzy borders: the taxonomic status and species limits of Saunders' vlei rat, Otomys saundersiae Roberts, 1929 (Rodentia, Muridae, Otomyini)
Authors: Taylor Peter John , Kumirai Albert , Contrafatto Giancarlo
Published: July 2007

The taxonomic status and species limits of the South African-endemic rodent
species Otomys saundersiae were revised using G-banding karyotypic analysis,
assessment of pelage colour and craniodental traits, multivariate analysis of
eight cranial distance measurements, and geometric morphometric analysis
of 11 landmarks of the dorsal image of the skull. In the Western Cape, the
recognized subspecies Otomys saundersiae karoensis differed in karyotype from
sympatrically-occurring populations of O. irroratus (cytotype "C") in having
six (as opposed to four) pairs of biarmed chromosome pairs and in the
absence of pair number 14. Discriminant analysis of linear craniometric
variables in positively identified (karyotyped) samples of Otomys irroratus and
Otomys s. karoensis separated the two species without any overlap, as did
pelage colour and certain qualitative cranial characters such as nasal angle;
such clear-cut differences however were not apparent between unkaryotyped
samples of O. s. saundersiae and O. irroratus from the Eastern Cape. Centroid
size (from geometric morphometric analysis of cranial landmarks) was
significantly correlated with both non-affine and affine components of skull
shape, indicating strong allometric effects. Both cranial shape and size differed significantly between Western Cape O. s. karoensis and O. irroratus; size, but not shape, varied significantly between Eastern Cape O. s. saundersiae and O. irroratus. Within both currently recognized species, significant geographical differences in cranial shape were detected between
eastern and western Cape populations occupying distinct ecological biomes.
Problems with defining species limits in this complex case were discussed
with reference to available data and alternative species concepts.
Going Public: Networking Globally and Locally*
Authors: Sachs Carolyn E.
Published: July 2007

Abstract  Rural sociologists figure prominently in the move towards public sociology. The paper takes up Michael Burawoy's call for public sociology and discusses what rural sociologists have to offer to publics and how we stand to gain as a discipline in working with publics. The paper argues that rural sociologists' ability to adopt a cosmopolitan view while negotiating the complexities of global/local processes provides a useful theoretical stance for doing public sociology. Methodologically, both feminist methods and various approaches to networks can guide us as we do public sociology. Then, the paper provides two examples of recent efforts to do public sociology with a women's community group in Sri Lanka in response to the tsunami and with the Pennsylvania Women's Agricultural Network to illustrate the possibilities and limitations of working with networks. In conclusion, the paper addresses opportunities for doing public sociology, the challenges we face as we go public, and future work that is needed to develop theoretically and methodologically strong public rural sociology.
Long-term storage of mouse spermatozoa after evaporative drying
Authors: Li Ming W , Biggers John D , Elmoazzen Heidi Y , Toner Mehmet , McGinnis Lynda , Lloyd K C Kent
Published: July 2007

To determine if mouse spermatozoa could be preserved long-term without using liquid nitrogen, mouse spermatozoa in trehalose–EGTA solution were partially evaporatively dried under nitrogen gas (5 min at flow rate10 l/min) and stored for 1 week and 5 months at 4, −20, and −80 °C before intracytoplasmic sperm injection. Fertilization rates were neither different with spermatozoa stored at 4, −20, or −80 °C for 1 week or 1, 3, and 5 months respectively, nor blastocyst formation rates with spermatozoa stored for 1 week and 1 month. However, spermatozoa stored at 4 and −20 °C for 3 months resulted in fewer blastocysts (35.1 and 54.3% respectively) when compared with spermatozoa stored at −80 °C (74.4%). Blastocyst formation rates using spermatozoa stored for 5 months at −20 °C (57.4%) or −80 °C (74.5%) were not significantly different from those stored for 3 months at the same temperatures respectively, but were significantly better than those stored for 5 months at 4 °C (10.2%). Blastocysts derived from spermatozoa stored for 3 and 5 months at −20 and −80 °C respectively, were then transferred to pseudopregnant mothers to develop into healthy liveborn offspring. No significant differences were found in embryo transfer rates (number of pups born/number of embryos transferred), weaning rates, or sex ratios of resultant pups, which were healthy and reproductively sound. These results demonstrate for the first time that partially evaporatively dried mouse spermatozoa in trehalose–EGTA solution can be preserved for long term at −20 and −80 °C. The possibility that the storage temperature must be less than the glass transition temperature is discussed.
Pairing and synapsis in oocytes from female fetuses with euploid and aneuploid chromosome complements
Authors: Robles P , Roig I , Garcia R , Ortega A , Egozcue J , Cabero L L , Garcia M
Published: July 2007

Only little is known about the meiotic prophase events in human oocytes, although some of them are involved in the origin of aneuploidies. Here, a broad study of the pairing and synaptic processes in 3263 human euploid and 2613 aneuploid oocytes (47,XX, +21 and 47,XX, +13), using different techniques and methods, is presented in order to elucidate the characteristics of this essential meiotic process. Our results reaffirm the existence of a common high efficiency in the pairing process leading to the obtainment of a bivalent for all chromosomes studied in euploid and aneuploid cases. Nevertheless, this high efficiency was insufficient to consistently produce trivalents in aneuploid oocytes. Trivalent 21 was only observed in 48.8% of the 47,XX, +21 pachytene-stage oocytes studied, and trivalent 13 was found in 68.7% of the 47,XX, +13 pachytene-stage oocytes analyzed. Our data confirm the hypothesis which suggests that in human oocytes the presence of an extra chromosome could interfere in bouquet dynamics. In addition, the pairing process of the X chromosome is altered in trisomic 21 oocytes, providing evidence of the influence that an extra chromosome 21 may cause meiotic progression.
The class II major histocompatibility complex molecule BoLA-DR is expressed by endothelial cells of the bovine corpus luteum
Authors: Cannon Matthew J , Davis John S , Pate Joy L
Published: July 2007

Cells expressing class II major histocompatibility complex (MHC) molecules are found within the corpus luteum (CL) of several species. Expression and localization of class II MHC molecules in the bovine CL were examined in the present study. Immunohistochemical evaluation revealed class II MHC molecules on single cells in early CL (days 4 and 5 post-estrus). Two class II MHC-expressing cell types were observed in midcycle CL (days 10–12 post-estrus), single cells similar to those observed in the early CL, and endothelial cells. Not all endothelial cells expressed class II MHC, and further investigation revealed expression of only one type of class II MHC molecule, DR, on endothelial cells. Class II MHC was also localized to endothelial cells in late CL (day 18 post-estrus). Steroidogenic luteal cells were negative for class II MHC throughout the estrous cycle. Quantitative RT-PCR revealed higher (P < 0.05) concentrations of mRNA encoding the α-subunit of DR (DRA) in late CL when compared with those in the early CL. DRA mRNA abundance was also measured in cultures of mixed luteal and luteal endothelial (CLENDO) cells, in the presence or absence of tumor necrosis factor-α (TNF). No differences were found in the DRA mRNA concentration between mixed luteal and CLENDO cell cultures, and TNF had no effect on DRA mRNA concentration in both cell types. Expression of DR by endothelial cells of the midcycle CL may induce anergy of T lymphocytes, or stimulate them to secrete products that enhance normal luteal function.
Molecular detection of adenovirus type 8 epidemic keratoconjunctivitis in Hungary
Authors: Reuter Gábor , Meleg Edina , Kiss Gabriella , Albert Nóra , Fekete Zsuzsanna , Szűcs György
Published: July 2007

Bevezetés:A heveny kötőhártya-gyulladás (conjunctivitis) fertőzéses és nem fertőzéses eredetű lehet. A fertőzéses eredetű járványos conjunctivitisek (conjunctivitis epidemica) kórokozói vírusok, ezen belül elsősorban az adenovírusok különböző típusai.Célkitűzés:A szerzők célja egy keratoconjunctivitis járvány epidemiológiai leírása volt a virális kórokozó molekuláris kimutatásával.Módszer:A járvány – részben retrospektív – felderítésében klasszikus járványügyi módszereket alkalmaztak. A laboratóriumi etiológiai vizsgálat az adenovírus hexon régiójának kimutatásával polimeráz láncreakcióval (PCR), majd szekvenálással történt frissen gyűjtött conjunctiva-váladékból.Eredmények:A keratoconjunctivitis járványban összesen 60-an betegedtek meg 2006. október 9. és december 18-a között hét baranyai településen. A betegek átlagéletkora 51,2 év volt. A vezető tünetek a conjunctiva belövelltsége (100%), a könnyezés (94%), az idegentest-érzés (83%) és a homályos látás (76%) voltak. Az esetek felében mindkét szem érintett volt. A fertőzés közvetlen kontaktussal terjedt részben nosocomiálisan, a szemészeti szakellátás során. Nyolc conjunctivaváladékból 5-ben (62,5%) genetikailag azonos, 8-as típusú adenovírust lehetett kimutatni (HAdV8/Baranya/2006/HUN; EF210714), mely 100%-ban azonos volt egy Ausztriában 2004-ben kimutatott adenovírussal (DQ149614).Következtetések:A részben a szemészeti ellátáshoz kapcsolódó nosocomiális keratoconjunctivitis-járványt az adenovírus 8-as típusa okozta. A megbetegedés klinikai felismerése, laboratóriumi diagnosztikája és a járványügyi intézkedések együttesen szükségesek a keratoconjunctivitis-fertőzések és a következményes járvány megelőzéséhez.
The Critical Period of Bengal Dayflower (Commelina Bengalensis) Control in Peanut
Authors: Webster Theodore M. , Faircloth Wilson H. , Timothy Flanders J. , Prostko Eric P. , Grey Timothy L.
Published: July 2007

Bengal dayflower (also known as tropical spiderwort) is one of the most troublesome weeds in peanut in Georgia, United States. Field studies conducted in 2004 and 2005 evaluated the relationship between the duration of Bengal dayflower interference and peanut yield in an effort to optimize the timing of weed control. In 2004, the critical period of weed control (CPWC) necessary to avoid greater than 5% peanut yield loss was between 316 and 607 growing degree days (GDD), which corresponded to an interval between June 8 and July 2. In 2005, the CPWC ranged from 185 to 547 GDD, an interval between May 30 and July 3. Maximum yield loss in 2005 from season-long interference of Bengal dayflower was 51%. In 2004, production of peanut pods was eliminated by interference with Bengal dayflower for the initial 6 wk (495 GDD) of the growing season. Robust Bengal dayflower growth in 2004 shaded the peanut crop, likely intercepting fungicide applications and causing a reduction in peanut yield. Therefore, the competitive effects of Bengal dayflower are likely complicated with the activity of plant pathogens. In spite of higher Bengal dayflower population densities, greater Bengal dayflower growth, and greater peanut yield losses in 2004 than in 2005, the CPWC was a relatively similar 4-wk period that ended during the first week of July, for peanut that was planted in the first week of May.
Immature and Neurally Differentiated Mouse Embryonic Stem Cells Do Not Express a Functional Fas/Fas Ligand System
Authors: Brunlid Gabriella , Pruszak Jan , Holmes Benjamin , Isacson Ole , Sonntag Kai-Christian
Published: July 2007

The potential of pluripotent embryonic stem (ES) cells to develop into functional cells or tissue provides an opportunity in the development of new therapies for many diseases including neurodegenerative disorders. The survival of implanted cells usually requires systemic immunosuppression, however, which severely compromises the host immune system, leading to complications in clinical transplantation. An optimal therapy would therefore be the induction of specific tolerance to the donor cells, while otherwise preserving functional immune responses. Fas ligand (FasL) is expressed in activated lymphocytes as well as cells in “immune-privileged” sites including the central nervous system. Its receptor, Fas, is expressed on various immune-reactive cell types, such as activated natural killer and T cells, monocytes, and polymorphic mononucleocytes, which can undergo apoptosis upon interaction with FasL. To render transplanted cells tolerant to host cellular immune responses, we genetically engineered mouse ES cells to express rat FasL (rFasL). The rFasL-expressing ES cells were analyzed for survival during in vitro neurodifferentiation and after transplantation to the rat brain without further immunosuppression. Although control transfected HEK-293T cells expressed functional rFasL, immature and differentiated mouse ES cells did not express the recombinant rFasL surface protein. Furthermore, there was no evidence for functional endogenous Fas and FasL expression on either ES cells or on neural cells after in vitro differentiation. Moreover, implanted rFasL-engineered ES cells did not survive in the rat brains in the absence of the immunosuppressive agent cyclosporine A. Our results indicate that immature and differentiated mouse ES cells do not express a functional Fas/FasL system.

Disclosure of potential conflicts of interest is found at the end of this article.