bluuebunny/crossref_metadata_2025 huggingface dataset:
Plants, Mycorrhizal Fungi, and Bacteria: A Network of Interactions
Authors: Bonfante Paola , Anca Iulia-Andra
Published: June 2009

This review focuses on interactions among plants, mycorrhizal fungi, and bacteria, testing the hypothesis whether mycorrhizas can be defined as tripartite associations. After summarizing the main biological features of mycorrhizas, we illustrate the different types of interaction occurring between mycorrhizal fungi and bacteria, from loosely associated microbes to endobacteria. We then discuss, in the context of nutritional strategies, the mechanisms that operate among members of the consortium and that often promote plant growth. Release of active molecules, including volatiles, and physical contact among the partners seem important for the establishment of the bacteria/mycorrhizal fungus/plant network. The potential involvement of quorum sensing and Type III secretion systems is discussed, even if the exact nature of the complex interspecies/interphylum interactions remains unclear.
Understanding protein synthesis: a role-play approach in large undergraduate human anatomy and physiology classes
Authors: Sturges Diana , Maurer Trent W. , Cole Oladipo
Published: June 2009

This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section presented with a traditional lecture served as the control group. A pretest/posttest assessment and a survey were administered to both sections and used in data analysis. In addition, overall test scores and item analysis were examined. The analysis revealed that participants in both groups improved significantly from pretest to posttest, but there were no significant differences between the groups in posttest scores. Neither group showed a significant change from posttest to the exam. However, there was a moderate positive effect on engagement and satisfaction survey questions from being in the study group (based on 255 total surveys returned by both groups). The role-play activity was at least as effective as the lecture in terms of student performance on the above-mentioned assessments. In addition, it proved successful in engaging students in the learning process and increasing their satisfaction.
Inhibition and Recurrent Excitation in a Computational Model of Sparse Bursting in Song Nucleus HVC
Authors: Gibb Leif , Gentner Timothy Q. , Abarbanel Henry D. I.
Published: June 2009

The telencephalic premotor nucleus HVC is situated at a critical point in the pattern-generating premotor circuitry of oscine songbirds. A striking feature of HVC's premotor activity is that its projection neurons burst extremely sparsely. Here we present a computational model of HVC embodying several central hypotheses: 1) sparse bursting is generated in bistable groups of recurrently connected robust nucleus of the arcopallium (RA)–projecting (HVCRA) neurons; 2) inhibitory interneurons terminate bursts in the HVCRA groups; and 3) sparse sequences of bursts are generated by the propagation of waves of bursting activity along networks of HVCRA neurons. Our model of sparse bursting places HVC in the context of central pattern generators and cortical networks using inhibition, recurrent excitation, and bistability. Importantly, the unintuitive result that inhibitory interneurons can precisely terminate the bursts of HVCRA groups while showing relatively sustained activity throughout the song is made possible by a specific constraint on their connectivity. We use the model to make novel predictions that can be tested experimentally.
Quantitative Assessment of the Complex Dynamics of G1, S, and G2-M Checkpoint Activities
Authors: Ubezio Paolo , Lupi Monica , Branduardi Davide , Cappella Paolo , Cavallini Edoardo , Colombo Valentina , Matera Giada , Natoli Claudia , Tomasoni Daniela , D'Incalci Maurizio
Published: June 2009

Although studies of cell cycle perturbation and growth inhibition are common practice, they are unable to properly measure the activity of cell cycle checkpoints and frequently convey misinterpretation or incomplete pictures of the response to anticancer treatment. A measure of the strength of the treatment response of all checkpoints, with their time and dose dependence, provides a new way to evaluate the antiproliferative activity of the drugs, fully accounting for variation of the cell fates within a cancer cell line. This is achieved with an interdisciplinary approach, joining information from independent experimental platforms and interpreting all data univocally with a simple mathematical model of cell cycle proliferation. The model connects the dynamics of checkpoint activities at the molecular level with population-based flow cytometric and growth inhibition time course measures. With this method, the response to five drugs, characterized by different molecular mechanisms of action, was studied in a synoptic way, producing a publicly available database of time course measures with different techniques in a range of drug concentrations, from sublethal to frankly cytotoxic. Using the computer simulation program, we were able to closely reproduce all the measures in the experimental database by building for each drug a scenario of the time and dose dependence of G1, S, and G2-M checkpoint activities. We showed that the response to each drug could be described as a combination of a few types of activities, each with its own strength and concentration threshold. The results gained from this method provide a means for exploring new concepts regarding the drug–cell cycle interaction. [Cancer Res 2009;69(12):5234–40]
Antitumor Activity with CYP17 Blockade Indicates That Castration-Resistant Prostate Cancer Frequently Remains Hormone Driven
Authors: Attard Gerhardt , Reid Alison H.M. , Olmos David , de Bono Johann S.
Published: June 2009

Abiraterone acetate is a potent, selective, and orally bioavailable small molecule inhibitor of CYP17, an enzyme that catalyzes two key serial reactions (17 alpha hydroxylase and 17,20 lyase) in androgen and estrogen biosynthesis. Clinical trials have confirmed that specific inhibition of CYP17 is safe and results in clinically important antitumor activity in up to 70% of castrate patients with advanced prostate cancer resistant to currently available endocrine therapies. These clinical data indicate that castration-resistant prostate cancer frequently remains hormone dependent and has confirmed that this disease should no longer be described as “hormone resistant or refractory”. Biomarker studies, including the analysis of ETS gene fusion status, on patients treated with abiraterone acetate may allow enrichment of patients with a sensitive phenotype in future studies of therapeutics targeting CYP17. [Cancer Res 2009;69(12):4937–40]
Dual Activity Lysophosphatidic Acid Receptor Pan-Antagonist/Autotaxin Inhibitor Reduces Breast Cancer Cell MigrationIn vitroand Causes Tumor RegressionIn vivo
Authors: Zhang Honglu , Xu Xiaoyu , Gajewiak Joanna , Tsukahara Ryoko , Fujiwara Yuko , Liu Jianxiong , Fells James I. , Perygin Donna , Parrill Abby L. , Tigyi Gabor , Prestwich Glenn D.
Published: June 2009

Signal transduction modifiers that modulate the lysophosphatidic acid (LPA) pathway have potential as anticancer agents. Herein, we describe metabolically stabilized LPA analogues that reduce cell migration and invasion and cause regression of orthotopic breast tumors in vivo. Two diastereoisomeric α-bromophosphonates (BrP-LPA) were synthesized, and the pharmacology was determined for five LPA G protein–coupled receptors (GPCRs). The syn and anti diastereomers of BrP-LPA are pan-LPA GPCR antagonists and are also nanomolar inhibitors of the lysophospholipase D activity of autotaxin, the dominant biosynthetic source of LPA. Computational models correctly predicted the diastereoselectivity of antagonism for three GPCR isoforms. The anti isomer of BrP-LPA was more effective than syn isomer in reducing migration of MDA-MB-231 cells, and the anti isomer was superior in reducing invasion of these cells. Finally, orthotopic breast cancer xenografts were established in nude mice by injection of MB-231 cells in an in situ cross-linkable extracellular matrix. After 2 weeks, mice were treated with the BrP-LPA alone (10 mg/kg), Taxol alone (10 mg/kg), or Taxol followed by BrP-LPA. All treatments significantly reduced tumor burden, and BrP-LPA was superior to Taxol in reducing blood vessel density in tumors. Moreover, both the anti- and syn-BrP-LPA significantly reduced tumors at 3 mg/kg. [Cancer Res 2009;69(13):5441–9]
Cells with Characteristics of Cancer Stem/Progenitor Cells Express the CD133 Antigen in Human Endometrial Tumors
Authors: Rutella Sergio , Bonanno Giuseppina , Procoli Annabella , Mariotti Andrea , Corallo Maria , Prisco Maria Grazia , Eramo Adriana , Napoletano Chiara , Gallo Daniela , Perillo Alessandro , Nuti Marianna , Pierelli Luca , Testa Ugo , Scambia Giovanni , Ferrandina Gabriella
Published: June 2009

Purpose: Cancer stem cells represent an attractive therapeutic target for tumor eradication. The present study aimed to determine whether CD133 expression may identify cells with characteristics of cancer stem/progenitor cells in human endometrial tumors.

Experimental Design: We analyzed 113 tumor samples for CD133/1 expression by flow cytometry, immunohistochemistry, and semiquantitative reverse transcription–PCR. CD133+ cells were isolated and used to assess phenotypic characteristics, self-renewal capacity, ability to maintain CD133 expression and form sphere-like structures in long-term cultures, sensitivity to chemotherapeutic agents, gene expression profile, and ability to initiate tumors in NOD/SCID mice.

Results: Primary tumor samples exhibited a variable degree of immunoreactivity for CD133/1, ranging from 1.3% to 62.6%, but stained negatively for other endothelial and stem cell–associated markers. Isolated CD133+ cells expanded up to 4.6-fold in serum-replenished cultures and coexpressed the GalNAcα1-O-Ser/Thr MUC-1 glycoform, a well-characterized tumor-associated antigen. Dissociated bulk tumors formed sphere-like structures; cells grown as tumor spheres maintained CD133 expression and could be propagated for up to 12 weeks. CD133+ cells purified from endometrioid adenocarcinomas were resistant to cisplatin-induced and paclitaxel-induced cytotoxicity and expressed a peculiar gene signature consisting of high levels of matrix metalloproteases, interleukin-8, CD44, and CXCR4. When serially transplanted into NOD/SCID mice, CD133+ cells were capable of initiating tumor formation and recapitulating the phenotype of the original tumor.

Conclusions: CD133 is expressed by human endometrial cancers and might represent a valuable tool to identify cells with cancer stem cell characteristics.
Copper Transporter 2 Regulates the Cellular Accumulation and Cytotoxicity of Cisplatin and Carboplatin
Authors: Blair Brian G. , Larson Christopher A. , Safaei Roohangiz , Howell Stephen B.
Published: June 2009

Purpose: Copper transporter 2 (CTR2) is known to mediate the uptake of Cu+1 by mammalian cells. Several other Cu transporters, including the influx transporter CTR1 and the two efflux transporters ATP7A and ATP7B, also regulate sensitivity to the platinum-containing drugs. We sought to determine the effect of CTR2 on influx, intracellular trafficking, and efflux of cisplatin and carboplatin.

Experimental Design: The role of CTR2 was examined by knocking down CTR2 expression in an isogenic pair of mouse embryo fibroblasts consisting of a CTR1+/+ line and a CTR1−/− line in which both CTR1 alleles had been deleted. CTR2 levels were determined by quantitative reverse transcription-PCR and Western blot analysis. Cisplatin (DDP) was quantified by inductively coupled plasma mass spectrometry and 64Cu and [14C]carboplatin (CBDCA) accumulation by γ and scintillation counting.

Results: Deletion of CTR1 reduced the uptake of Cu, DDP, and CBDCA and increased resistance to their cytotoxic effects by 2- to 3-fold. Knockdown of CTR2 increased uptake of Cu only in the CTR1+/+ cells. In contrast, knockdown of CTR2 increased whole-cell DDP uptake and DNA platination in both CTR1+/+ and CTR1−/− cells and proportionately enhanced cytotoxicity while producing no effect on vesicular accumulation or efflux. A significant correlation was found between CTR2 mRNA and protein levels and sensitivity to DDP in a panel of six ovarian carcinoma cell lines.

Conclusions: CTR2 is a major determinant of sensitivity to the cytotoxic effects of DDP and CBDCA. CTR2 functions by limiting drug accumulation, and its expression correlates with the sensitivity of human ovarian carcinoma cell lines to DDP.
Tissue Targeting in Cancer: eIF4E's Tale
Authors: Borden Katherine L.B.
Published: June 2009

The eukaryotic translation initiation factor eIF4E is elevated in many human cancers. Tissue-specific targeting of eIF4E activity in ovarian cancer cells is achieved in cell culture and in mice by fusing a peptide corresponding to the eIF4E inhibitor, the eIF4E binding protein 1 (BP1), to an agonist of the gonadotropin receptor.
Photodynamic Therapy: A Light in the Darkness?
Authors: Lin Alexander , Hahn Stephen M.
Published: June 2009

Photodynamic therapy (PDT) is used to treat localized premalignant or early malignant disease. This study reports the enhanced, systemic antitumor immune response from PDT, suggesting that it may have a potential role as a therapy to address both local and disseminated disease.
Epigenetics in cancer: Targeting chromatin modifications
Authors: Ellis Leigh , Atadja Peter W. , Johnstone Ricky W.
Published: June 2009

Posttranslational modifications to histones affect chromatin structure and function resulting in altered gene expression and changes in cell behavior. Aberrant gene expression and altered epigenomic patterns are major features of cancer. Epigenetic changes including histone acetylation, histone methylation, and DNA methylation are now thought to play important roles in the onset and progression of cancer in numerous tumor types. Indeed dysregulated epigenetic modifications, especially in early neoplastic development, may be just as significant as genetic mutations in driving cancer development and growth. The reversal of aberrant epigenetic changes has therefore emerged as a potential strategy for the treatment of cancer. A number of compounds targeting enzymes that regulate histone acetylation, histone methylation, and DNA methylation have been developed as epigenetic therapies, with some demonstrating efficacy in hematological malignancies and solid tumors. This review highlights the roles of epigenetic modifications to histones and DNA in tumorigenesis and emerging epigenetic therapies being developed for the treatment of cancer. [Mol Cancer Ther 2009;8(6):1409–20]
Regulated cell death pathways: New twists in modulation of BCL2 family function
Authors: Sasi Nidhish , Hwang Misun , Jaboin Jerry , Csiki Ildiko , Lu Bo
Published: June 2009

A number of cell death pathways have been recognized. Though apoptosis and autophagy have been well characterized, programmed necrosis has recently received attention and may provide clinical alternatives to suppress resistant tumors. Necrosis is primarily characterized by large-scale permeabilization, swelling, and rupture of cell membranes and the release of pro-inflammatory cytokines. Traditionally, necrosis in cancer cells has been indicative of poor prognoses, as chronic inflammation was found to encourage tumor growth. Yet, many antitumor effects associated with necrosis have been discovered in certain settings, such as the formation of an effective antitumor immune response. In this way, finding ways to attenuate the pro-tumor effects of necrosis while engaging the antitumor pathways via drugs, radiation, and sensitization may prove valuable as a clinical focus for the future. We hypothesize that the use of Bcl-2 inhibitors may enhance necrotic death characterized by inflammation and antitumor immunity. In this article, we briefly review apoptosis and autophagy and reason how necrosis may be a suitable alternative therapeutic endpoint. We then highlight novel inhibitors of Bcl-2 that may provide clinical application of our hypothesis in the future. [Mol Cancer Ther 2009;8(6):1421–9]
Hypoxia prevents etoposide-induced DNA damage in cancer cells through a mechanism involving hypoxia-inducible factor 1
Authors: Sullivan Richard , Graham Charles H.
Published: June 2009

Intratumoral hypoxia is associated with resistance to therapy in many human cancers, and preexposure of tumor cells to hypoxia confers multidrug resistance. Whereas most anticancer drugs kill proliferating tumor cells by causing DNA damage, a role for hypoxia in the prevention and/or repair of drug-induced DNA damage has not been clear. Using the alkaline comet assay, we provide direct evidence that hypoxia-induced resistance to etoposide in human tumor cells (MDA-MB-231 breast carcinoma and DU-145 prostatic adenocarcinoma) is mainly due to prevention of drug-induced DNA damage (i.e., strand breaks) and that the amount of DNA damage present immediately after etoposide exposure is a good independent predictor of clonogenic survival. Our results also revealed that preexposure to hypoxia did not affect the apparent DNA repair capacity of cells. These findings indicate that the extent of DNA damage resulting from etoposide exposure is a more important determinant of survival than subsequent events after DNA damage. Furthermore, immunofluorescence analysis showed that, in a subpopulation of cells, preexposure to hypoxia decreased the levels of topoisomerase IIα, an enzyme that generates DNA strand breaks when poisoned with etoposide. Treatment of cells with small interfering RNA targeting hypoxia-inducible factor 1 prevented the hypoxia-induced decreases in topoisomerase IIα levels, abolished the protective effect of hypoxia against etoposide-induced DNA damage, and inhibited hypoxia-induced etoposide resistance. These findings support a model of hypoxia-induced drug resistance in which etoposide-induced DNA damage is prevented by HIF-1–dependent adaptations to hypoxia. [Mol Cancer Ther 2009;8(6):1702–13]
Silibinin inhibits translation initiation: implications for anticancer therapy
Authors: Lin Chen-Ju , Sukarieh Rami , Pelletier Jerry
Published: June 2009

Silibinin is a nontoxic flavonoid reported to have anticancer properties. In this study, we show that silibinin exhibits antiproliferative activity on MCF-7 breast cancer cells. Exposure to silibinin leads to a concentration-dependent decrease in global protein synthesis associated with reduced levels of eukaryotic initiation factor 4F complex. Moreover, polysome profile analysis of silibinin-treated cells shows a decrease in polysome content and translation of cyclin D1 mRNA. Silibinin exerts its effects on translation initiation by inhibiting the mammalian target of rapamycin signaling pathway by acting upstream of TSC2. Our results show that silibinin blocks mammalian target of rapamycin signaling with a concomitant reduction in translation initiation, thus providing a possible molecular mechanism of how silibinin can inhibit growth of transformed cells. [Mol Cancer Ther 2009;8(6):1606–12]
Angiotensin-(1-7) inhibits tumor angiogenesis in human lung cancer xenografts with a reduction in vascular endothelial growth factor
Authors: Soto-Pantoja David R. , Menon Jyotsana , Gallagher Patricia E. , Tallant E. Ann
Published: June 2009

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous seven-amino acid peptide hormone with antiproliferative properties. Our previous studies showed that Ang-(1-7) inhibits the growth of human lung cancer cells in vitro and reduces the size of human lung tumor xenografts in vivo. In the current study, s.c. injection of Ang-(1-7) not only caused a significant reduction in human A549 lung tumor growth but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. A decrease in human endothelial cell tubule formation in Matrigel was observed following a 16 h incubation with Ang-(1-7), with a maximal reduction at a 10 nmol/L concentration. Ang-(1-7) had similar antiangiogenic effects in the chick chorioallantoic membrane, causing a >50% decrease in neovascularization. The Ang-(1-7)-induced reduction in both endothelial cell tubule formation and vessel formation in the chick was completely blocked by the specific Ang-(1-7) receptor antagonist [d-proline7]-Ang-(1-7), suggesting that these biological actions are mediated by an AT(1-7) receptor. Ang-(1-7) significantly reduced vascular endothelial growth factor-A protein and mRNA in tumors from mice treated with the heptapeptide compared with saline controls as well as in the parent A549 human lung cancer cells in culture. These results suggest that Ang-(1-7) may attenuate tumor angiogenesis by reducing vascular endothelial growth factor-A, a primary proangiogenic protein. Taken together, this study shows that Ang-(1-7) exhibits significant antiangiogenic activity and may be a novel therapeutic agent for lung cancer treatment targeting a specific AT(1-7) receptor. [Mol Cancer Ther 2009;8(6):1676–83]
Women’s Expectations and Intention to Terminate Pregnancy in Case of Abnormal Findings at the Second Trimester Level II Ultrasound Scan
Authors: Athanasiadis Apostolos P. , Polychronou Paris , Mikos Themistoklis , Pantazis Konstantinos , Assimakopoulos Efstratios , Tzevelekis Filippos , Bontis John N.
Published: June 2009

Objective: The aims of this study were: (1) to explore pregnant women’s background knowledge and expectations of 2nd trimester ultrasound screening, and (2) to investigate women’s intentions to proceed to pregnancy termination if fetal anomaly is detected at the 2nd trimester ultrasound screening. Methods: A prospective, cross-sectional, questionnaire-based study. 300 consecutive pregnant women served as a convenience sample for this study. All the women had had a detailed, 2nd trimester, fetal anomaly scan. The questionnaire was a standardized but not validated, purpose-built structure consisting of five parts: (a) demographics, (b) anamnesis and obstetric history, (c) perceived aim of the scan, (d) expectations from the scan, and (e) intention to terminate pregnancy in case of fetal malformation diagnosis. Statistical analysis was performed with the SPSS 12.0 for Windows. Results: The participants’ mean age was 31.3 (21–45) years. 89.3% of the women filled in the questionnaire. The main reasons for the scan, according to the women, were to exclude fetal abnormalities and to assess the fetal karyotype. The main maternal expectations from the scan were to reduce maternal anxiety and to identify fetal malformations. 75.3% of the women were willing to terminate their pregnancy if fetal abnormalities were detected. Older women more commonly opted for pregnancy termination. Conclusion: The majority of participants have a correct notion about the aim of the ultrasound scan, their expectation is mainly anxiety reduction and a high percentage would proceed to pregnancy termination in the event of the detection of a fetal abnormality.
Fetal Hydrops, Hyperechogenic Arteries and Pathological Doppler Findings at 29 Weeks: Prenatal Presentation of Generalized Arterial Calcification of Infancy – A Novel Mutation in ENPP1
Authors: Reitter A. , Fischer D. , Buxmann H. , Nitschke Y. , Rutsch F. , Mottok A. , Hansmann M.L. , Harms E. , Louwen F. , Schlösser R.
Published: June 2009

Prenatal diagnosis of generalized arterial calcification of infancy (GACI) (OMIM #208000) is difficult and rare. There are various known gene mutations in ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) locus 6q22-q23. We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauterine therapy with bisphosphonates was considered, but delayed due to rapid deterioration in fetal Doppler flows with suspected fetal asphyxia. The couple was informed about the most unfavorable prognosis in fetal hydrops, however, they opted for elective delivery. A cesarean section was performed. Early neonatal death occurred due to primary intracranial hemorrhage. Postmortem and genetic testing confirmed a novel mutation in the ENPP1 gene.
Exercise and Mental Health: Many Reasons to Move
Authors: Deslandes Andréa , Moraes Helena , Ferreira Camila , Veiga Heloisa , Silveira Heitor , Mouta Raphael , Pompeu Fernando A.M.S. , Coutinho Evandro Silva Freire , Laks Jerson
Published: June 2009

The relationship between physical activity and mental health has been widely investigated, and several hypotheses have been formulated about it. Specifically, during the aging process, physical exercise might represent a potential adjunctive treatment for neuropsychiatric disorders and cognitive impairment, helping delay the onset of neurodegenerative processes. Even though exercise itself might act as a stressor, it has been demonstrated that it reduces the harmful effects of other stressors when performed at moderate intensities. Neurotransmitter release, neurotrophic factor and neurogenesis, and cerebral blood flow alteration are some of the concepts involved. In this review, the potential effects of exercise on the aging process and on mental health are discussed, concerning some of the recent findings on animal and human research. The overwhelming evidence present in the literature today suggests that exercise ensures successful brain functioning.
Intraoperative and Postoperative Outcome of Robot-Assisted and Traditional Laparoscopic Nissen Fundoplication
Authors: Ceccarelli G. , Patriti A. , Biancafarina A. , Spaziani A. , Bartoli A. , Bellochi R. , Casciola L.
Published: June 2009

Background: Robotics has been proposed as a tool to improve laparoscopic Nissen fundoplication. However, a clear benefit of this technology for minimally invasive antireflux surgery has not been demonstrated. Materials and Methods: A retrospective review of a prospective database was used to compare the intraoperative and postoperative outcome of 137 patients who underwent conventional laparoscopic fundoplication (CLF) and 45 patients who underwent laparoscopic robot-assisted fundoplication (LRF). Intraoperative outcome measures were: operative time, blood loss and complications. Length of hospital stay, functional results and patient satisfaction were used to compare postoperative outcome. Results: Operative time was significantly shorter in the LRF group (65 min) compared to the CLF group (85 min) (p < 0.0001). The overall complication rate was comparable between the two techniques, even though a higher incidence of liver tears was encountered in the CLF group (p < 0.05). Hospital stay, symptom relief and patient satisfaction did not differ between the groups. Conclusion: Robotics improves surgeon dexterity and maneuverability during laparoscopic Nissen fundoplication, but this does not correspond to a better postoperative outcome. LRF should be used only for complex cases and training.
mRNA of Placental Origin in Maternal Serum of Women with Normal and Preeclamptic Pregnancies
Authors: Schmidt Markus , Hoffmann Barbara , Kimmig Rainer , Kasimir-Bauer Sabine
Published: June 2009

Objective: We quantified placenta-specific mRNA from maternal blood to evaluate differences in normal and preeclamptic pregnancies. Methods: mRNA was purified from 560 μl serum using the QIAamp® Viral RNA Mini Kit in 8 women with normal and 8 women with preeclamptic pregnancies. Results: The relative amounts for β-hCG, CRH and hPL in serum samples of each study group showed a broad variety in the expression levels within one group. Higher amounts for CRH were found in most cases of preeclampsia, for β-hCG and hPL the amounts for women with preeclamptic pregnancies were tenfold below the values found for normal pregnancies. Conclusion: This method is not useful to distinguish between normal and preeclamptic pregnancies in the second trimester and later. Whether it can be applied for early diagnosis of preeclampsia has to be elucidated in further studies.
Array Comparative Genomic Hybridization in Prenatal Diagnosis: Another Experience
Authors: Vialard F. , Molina Gomes D. , Leroy B. , Quarello E. , Escalona A. , Le Sciellour C. , Serazin V. , Roume J. , Ville Y. , de Mazancourt P. , Selva J.
Published: June 2009

Objectives: Etiologic diagnosis of multiple congenital abnormalities (MCAs) is often lacking. Large chromosome abnormalities can be detected by conventional cytogenetic methods, but more subtle chromosome micro-rearrangements and/or de novo abnormalities require multi-FISH analysis, which is hampered by the amount of material available in prenatal testing. Methods: We used the comparative genomic hybridization (CGH) array, Genosensor™ Array 300, to screen for classic microdeletion syndromes and subtelomeric rearrangements in 39 consecutive fetuses with MCAs, after termination of pregnancy, in a prospective study. Thirty-seven of them had a normal karyotype, and two had a de novo unbalanced karyotype that could not be characterized with conventional cytogenetic methods. Results: Two de novo unbalanced karyotypes were characterized by array CGH, and four additional abnormalities were diagnosed: an unbalanced inherited cryptic translocation, a deletion in band 22q11.2, a 1p36 deletion, and a 6p12.1–21.2 duplication. Conclusion: Chromosomal imbalances were therefore detected and/or characterized in 6 of 39 (15.4%) fetuses, indicating the value of routine array CGH in cases of MCAs and in uncharacterized chromosome rearrangements. Extension to all prenatal diagnoses may be warranted when copy number variation is identified and all FISH probes are commercially available.
Is Rapid Aneuploidy Screening Used Alone Acceptable in Prenatal Diagnosis? An Evaluation of the Possible Role of Ultrasound Examination
Authors: Gaudry P. , Lebbar A. , Choiset A. , Girard S. , Lewin F. , Tsatsaris V. , Grangé G.
Published: June 2009

Objective: The objectives of this study were to use a factual basis to: (1) determine the number, nature, and probable phenotypic consequences of karyotype anomalies that would probably be missed (structural anomalies, uncommon aneuploidies and mosaic aneuploidies) by rapid aneuploidy screening (RAS), and (2) appraise whether RAS can replace traditional karyotyping when amniocenteses are performed for increased risk of Down’s syndrome by maternal serum screening or advanced maternal age in the absence of ultrasound abnormality. Methods: This retrospective cohort study analysed the indications, results and outcomes of 5,713 consecutive amniocenteses over a 5-year period at a single prenatal diagnosis centre in Paris. Results: Advanced maternal age and increased Down’s risk with maternal serum marker were the most common indications. Chromosome abnormalities were detected in 3.64% of the pregnancies tested, and unexpected structural anomalies in 0.63% (n = 36). Translocations were more likely to be reciprocal, balanced and of parental origin. There were 6 mosaic gonosomal aneuploidies. Overall, 4 mosaic autosomal aneuploidies and 36 structural aberrations would not have been recognised by RAS alone. Of the 4 mosaic autosomal aneuploidies, all were terminated, one had major malformations and the others had discrete signs that a good quality ultrasound examination would probably not detect. Of the 36 structural aberrations, 24 would be undetected by ultrasound scan, from which 6 would be associated with a significant risk of an abnormal phenotype outcome. Conclusion: In conclusion, our data do not provide evidence that RAS can replace the traditional karyotype. It is probably impossible to arrive in a universal conclusion of which approach (karyotype or RAS) is definitely better than the other. Each prenatal centre could have its own approach depending on the local data analysis, including quality control of ultrasounds.
Mother’s Genome or Maternally-Inherited Genes Acting in the Fetus Influence Gestational Age in Familial Preterm Birth
Authors: Plunkett Jevon , Feitosa Mary F. , Trusgnich Michelle , Wangler Michael F. , Palomar Lisanne , Kistka Zachary A.-F. , DeFranco Emily A. , Shen Tammy T. , Stormo Adrienne E.D. , Puttonen Hilkka , Hallman Mikko , Haataja Ritva , Luukkonen Aino , Fellman Vineta , Peltonen Leena , Palotie Aarno , Daw E. Warwick , An Ping , Teramo Kari , Borecki Ingrid , Muglia Louis J.
Published: June 2009

Objective: While multiple lines of evidence suggest the importance of genetic contributors to risk of preterm birth, the nature of the genetic component has not been identified. We perform segregation analyses to identify the best fitting genetic model for gestational age, a quantitative proxy for preterm birth. Methods: Because either mother or infant can be considered the proband from a preterm delivery and there is evidence to suggest that genetic factors in either one or both may influence the trait, we performed segregation analysis for gestational age either attributed to the infant (infant’s gestational age), or the mother (by averaging the gestational ages at which her children were delivered), using 96 multiplex preterm families. Results: These data lend further support to a genetic component contributing to birth timing since sporadic (i.e. no familial resemblance) and nontransmission (i.e. environmental factors alone contribute to gestational age) models are strongly rejected. Analyses of gestational age attributed to the infant support a model in which mother’s genome and/or maternally-inherited genes acting in the fetus are largely responsible for birth timing, with a smaller contribution from the paternally-inherited alleles in the fetal genome. Conclusion: Our findings suggest that genetic influences on birth timing are important and likely complex.
Intramuscular Immunization with a Plasmid DNA Vaccine Encoding prM-E Protein from Japanese Encephalitis Virus: Enhanced Immunogenicity by Co-Administration of GM-CSF Gene and Genetic Fusions of prM-E Protein and GM-CSF
Authors: Zhai Yong-zhen , Li Xi-mei , Zhou Yan , Ma Li , Feng Guo-he
Published: June 2009

Objective: To investigate the immune responses elicited by pJME with or without various forms of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene. Methods: The changes of the T lymphocyte subsets and the levels of Th cell intracellular cytokines IFN-γ and IL-4 were evaluated by flow cytometric analysis. The cytotoxic T lymphocyte kill activity was assessed by lactate dehydrogenase activity release test. An 80% plaque reduction neutralization test was performed to titrate the neutralization antibody before and after viral challenge. Results: We demonstrated that simultaneous administration of pJME plus plasmid-ecoded GM-CSF (pGM-CSF) activated Th1 immune responses similar to those found by injecting pGM-CSF i.m. into mice 3 days before pJME vaccination, and enhancement of Th2 immunity predominated when the pGM-CSF was injected 3 days after pJME vaccination. Furthermore, the immunization with DNA vaccine encoding precursor membrane envelope/GM-CSF fusion protein was more effective in generating immune responses than that induced by immunization with pJME alone or in combination with pGM-CSF. Conclusions: These observations support the potential of GM-CSF DNA adjuvant for the Th1/Th2 balance and the enhancement of immune responses by showing that the timing of the administration of pGM-CSF and the application of different forms of GM-CSF gene influence the outcome of the resultant immune responses.
Prevalence and Antimicrobial Susceptibility of Extended-Spectrum Beta-Lactamase-Producing Bacteria in Intensive Care Units of Sanandaj General Hospitals (Kurdistan, Iran)
Authors: Ramazanzadeh Rashid , Chitsaz Mohsen , Bahmani Nasrin
Published: June 2009

This study focused on analyzing the spread of extended-spectrum β-lactamase (ESBL) enzymes among Gram-negative bacteria at intensive care units (ICUs). Between January 2007 and January 2008, 301 consecutive clinical isolates of Gram-negative type were isolated. Of these, 66 strains were collected from patients in ICUs in two major hospitals in Sanandaj (Kurdistan, Iran). The isolates were identified, tested for antimicrobial susceptibility, and analyzed for the presence of ESBL using the double-disk synergy test. Isolates with a positive ESBL phenotype were subjected to PCR for SHV, TEM, OXA and CTX-M β-lactamase gene families. Sixty-six Gram-negative bacteria were isolated from clinical samples of 66 ICU patients. These isolates included 16 Escherichia coli, 28 Enterobacter spp., 5 Pseudomonas spp., 10 Klebsiella pneumoniae, 3 Serratia marcescens and 1 Stenotrophomonas maltophilia. Twenty-three (34.85%) of these isolates were ESBL producing. The ESBL genes detected were SHV, TEM, OXA-1, OXA-2 and CTX-M. The results show the presence of ESBL genes among Gram-negative bacteria in the ICU setting of Sanandaj’s hospitals. There is a need to institute a strict hospital infection control policy and regular surveillance of bacterial resistance to antimicrobial agents.
Should Patient Characteristics Influence Target Anticoagulation Intensity for Stroke Prevention in Nonvalvular Atrial Fibrillation?
Authors: Singer Daniel E. , Chang Yuchiao , Fang Margaret C. , Borowsky Leila H. , Pomernacki Niela K. , Udaltsova Natalia , Go Alan S.
Published: June 2009

Background—

Randomized trials and observational studies support using an international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic stroke in atrial fibrillation. We assessed whether the INR target should be adjusted based on selected patient characteristics.

Methods and Results—

We conducted a case–control study nested within the ATRIA cohort’s 9217 atrial fibrillation patients taking warfarin to define the relationship between INR level and the odds of thromboembolism (TE; mainly stroke) and of intracranial hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164 ICH cases during follow-up. Each case was compared with 4 randomly selected controls matched on calendar date and stroke risk factors using matched univariable analyses and conditional logistic regression. We explored modification of the INR–outcome relationships by the following stroke risk factors: prior stroke, age, and CHADS
2
risk score. Overall, the odds of TE were low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19, at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg, odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at INR levels <2.0. These patterns of risk did not differ substantially by history of stroke, age, or CHADS
2
risk score.

Conclusions—

Our results confirm that the current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal INR range. Our findings do not support adjustment of INR targets according to previously defined stroke risk factors.
Babes in the Woods: Wilderness Aesthetics in Children's Stories and Toys, 1830-1915
Authors: Varga Donna
Published: June 2009

Representations of nonhuman wild animals in children's stories and toys underwent dramatic transformation over the years 1830-1915. During the earlier part of that period, wild animals were presented to children as being savage and dangerous, and that it was necessary for them to be killed or brutally constrained. In the 1890s, an animalcentric discourse emerged in Nature writing, along with an animal-human symbiosis in scientific child study that highlighted childhood innocence, resulting in a valuing of wild animals based upon their similarity to humans. This article will describe the aesthetic devices of children's stories and play materials in relation to the dominant, emerging, and residual ideas about the wild communicated by adults to children through these means.
Birdsong and the Image of Evolution
Authors: Mundy Rachel
Published: June 2009

For nearly a quarter of Darwin's Descent of Man (1871), it is the singing bird whose voice presages the development of human aesthetics. But since the 1950s, aesthetics has had a perilous and contested role in the study of birdsong. Modern ornithology's disillusionment with aesthetic knowledge after World War II brought about the removal of musical studies of birdsong, studies which were replaced by work with the sound spectrograph, a tool that changes the elusive sounds of birdsong into a readable graphic image called a spectrogram. This article narrates the terms under which the image, rather than the sound, of birdsong has become a sign of humanity's ability to reason objectively. Drawing examples from the strange evolutionary tales that exist at the juncture of ornithology, music history, illustration, and linguistics, this story suggests how it was that the human ear disappeared in the unbridgeable gap between the sciences and the study of aesthetics so tellingly termed "the humanities."
Sociology and Beyond: Cultivating an Ontological Epistemology of Participation
Authors: Giri Ananta Kumar
Published: June 2009

Sociology reflects some of the fundamental assumptions of modernity. As an enterprise of knowledge, sociology reflects the modernistic privileging of epistemology to the neglect of ontological cultivation. The present article seeks to go beyond some of our modernistic limitations and cultivate sociology as a creative engagement in ontological epistemology of participation.
Exploring Practical Horizons of Beyond Sociology: Structure, Agency, and Strategy among Tenants in India
Authors: Olsen Wendy
Published: June 2009

A theoretical orientation toward 'strategies' is proposed in this paper. This theoretical approach suggests that we study both the context for immediate decision-making and the broader context in which reflection and deliberation occur. Whilst these are very broad concerns, the paper itself is based on fieldwork about land rental relationships in rural South India. The paper introduces strategies as a solution to the theorists' dilemma of choice vs. constraints. We treat tenants (as both households and as individual agents) in their structural contexts whilst respecting the complexity and co-mutuality of their agency. The strategies that people use involve an orientation to current and future events, including possible events which are imagined or which could happen. Both structural relationships and concrete past incidents act as reference points for decisions made today in a given relationship. The strategies of tenants include being pliable vis-à-vis landlords but some tenants make this conditional upon landlords' proper behaviour. Agents negotiate and enforce proper behaviour and, thus, both create and change the system of norms that exists. In Macintyre's terms (1985), the virtues intrinsic to the socio-economic practices are continually being re-worked. The theory of strategies reframes 'virtue' in dynamic structure-and-agency terms. Agents are not simply individuals. The debate about rational choice vs. holism can be augmented by looking at agency supra-individualistically. The strategy of a household is an emergent property of the household as an agent. It includes detailed first-order strategies along with more reflective second-order strategies which reconcile goals in the education, migration, household work, and marriage domains. The paper is, thus, interdisciplinary and contributes to sociology, while pluralistically drawing upon other disciplines.
What is Social Capital? A Comprehensive Review of the Concept
Authors: Bhandari Humnath , Yasunobu Kumi
Published: June 2009

Social capital is an old concept but it entered into academic and policy debates only in 1990s. Its importance in explaining economic and social phenomena have been increasingly felt in recent years. Literature on theoretical and empirical aspects of social capital grew significantly during last decade. The whole notion of social capital is centred on social relationships and its major elements include social networks, civic engagement, norms of reciprocity, and generalised trust. Broadly speaking, it is defined as a collective asset in the form of shared norms, values, beliefs, trust, networks, social relations, and institutions that facilitate cooperation and collective action for mutual benefits. It is a complex multidimensional concept having different dimensions, types, and levels of measurement. Common types of social capital include: structure and cognitive; bonding, bridging, and linking; strong and weak; and horizontal and vertical. It can be measured and analysed at individual- and collective-levels in terms of social perspective and micro-, meso- and macro-levels in terms of geographic perspective. The properties of social capital, such as capacity to appear in as an explanatory variable in the production function, accumulation over time, capability of improving economic performance, investment with expected future returns, convertibility, and the need of maintenance, make it qualify as a form of capital, though there are some criticisms about the use of term 'capital' in social capital. Research on social capital remains in its initial stage and the concept is still elusive, prone to contextual definition, deficient in common measurement indicators, inability to explicitly quantify effects, and subject to various criticisms. Conceptual and measurement imprecision has led the concept prone to vague interpretation, less empirical application, and underestimation of its value. More empirical studies and testing of the concept on the ground is needed to develop a commonly accepted definition and measurement indicators that can explicitly disentangle and quantify its effects on overall development processes. Better conceptualisation and operationalisation of social capital theory is helpful to attract more investment on its development, design appropriate social policies, and promote sustainable development.
China's Pragmatic Approach to Modernisation
Authors: Michael Heng Siam Heng
Published: June 2009

The book studies China's record of modernization in its own terms. The course charted by the Chinese leadership has certainly produced remarkable successes. It is a journey of economic reforms based on pragmatism, and the same thinking is guiding the ongoing legal reforms. There is no denial that the leaders are reluctant to embark on radical political reforms that may unseat them. At the same time, one must be informed by the historical experience of the Chinese people. The havocs and sufferings associated with radical political changes have made them risk averse, and the ruling Communist Party of China is shrewd enough to exploit this feeling. Based on empirical data on countries with similar income level, Peerenboom argues for democratic reform to occur after a certain level of economic development. This point is controversial but there is inadequate data to disprove him. However, even with the limitation of one-party rule, there are a few areas where the CPC can do a better job in bringing China further along the road to modernization.